PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 11896473-1 2002 Sildenafil improves erectile function by inhibiting the cGMP-catalytic activity of phosphodiesterase type V (PDE5). Cyclic GMP 56-60 phosphodiesterase 5A Homo sapiens 109-113 11805217-9 2002 Simultaneous inhibition of PDE5, 6, and 9 (zaprinast), purported to specifically elevate intracellular cGMP, reduced, in a dose-independent manner, IL-6 and TNF-alpha biosynthesis. Cyclic GMP 103-107 phosphodiesterase 5A Homo sapiens 27-41 11891572-5 2002 A large portion of the total cGMP hydrolysis detected in cytosolic and membrane fractions of T84 cells was mediated by PDE5 (50-75%). Cyclic GMP 29-33 phosphodiesterase 5A Homo sapiens 119-123 12836729-2 2002 The mechanism of action involves active inhibition of the PDE-5 enzyme and resulting increase in cyclic guanosine monophosphate (cGMP) and smooth muscle relaxation in the penis. Cyclic GMP 97-127 phosphodiesterase 5A Homo sapiens 58-63 12836729-2 2002 The mechanism of action involves active inhibition of the PDE-5 enzyme and resulting increase in cyclic guanosine monophosphate (cGMP) and smooth muscle relaxation in the penis. Cyclic GMP 129-133 phosphodiesterase 5A Homo sapiens 58-63 12027779-1 2002 Vardenafil selectively inhibits phosphodiesterase type 5 (PDE5), an enzyme which hydrolyses cyclic guanosine monophosphate in the cavernosum tissue of the penis. Cyclic GMP 92-122 phosphodiesterase 5A Homo sapiens 32-56 12027779-1 2002 Vardenafil selectively inhibits phosphodiesterase type 5 (PDE5), an enzyme which hydrolyses cyclic guanosine monophosphate in the cavernosum tissue of the penis. Cyclic GMP 92-122 phosphodiesterase 5A Homo sapiens 58-62 11747988-1 2002 The structure of cyclic GMP (cGMP)-binding (cGB), cGMP specific phosphodiesterase (PDE5) comprises several domains. Cyclic GMP 17-27 phosphodiesterase 5A Homo sapiens 83-87 11747988-1 2002 The structure of cyclic GMP (cGMP)-binding (cGB), cGMP specific phosphodiesterase (PDE5) comprises several domains. Cyclic GMP 29-33 phosphodiesterase 5A Homo sapiens 83-87 12479016-6 2002 CONCLUSIONS: The PDE5 gene ASON had been showed to manifest stimulative effect on the cGMP in smooth muscle cells of human corpus cavernosum in vitro, and it provides experimental groundwork for the gene therapy of erectile dysfunction. Cyclic GMP 86-90 phosphodiesterase 5A Homo sapiens 17-21 11285263-5 2001 To identify the structural determinants for the inhibitory interaction with Pgamma and the remarkable cGMP hydrolytic ability, we sought to reproduce the PDE6 characteristics by mutagenesis of PDE5, a related cyclic GMP-specific, cGMP-binding PDE. Cyclic GMP 102-106 phosphodiesterase 5A Homo sapiens 193-197 11597484-4 2001 From this study, we have clearly demonstrated that introduction of a carboxylic acid group to the 5"-sulfonamide moiety of the phenyl ring greatly enhanced PDE5 inhibitory activity, probably by mimicking the phosphate group of cGMP. Cyclic GMP 227-231 phosphodiesterase 5A Homo sapiens 156-160 11602184-0 2001 The gamma subunit of the rod photoreceptor cGMP phosphodiesterase can modulate the proteolysis of two cGMP binding cGMP-specific phosphodiesterases (PDE6 and PDE5) by caspase-3. Cyclic GMP 43-47 phosphodiesterase 5A Homo sapiens 158-162 11602184-0 2001 The gamma subunit of the rod photoreceptor cGMP phosphodiesterase can modulate the proteolysis of two cGMP binding cGMP-specific phosphodiesterases (PDE6 and PDE5) by caspase-3. Cyclic GMP 102-106 phosphodiesterase 5A Homo sapiens 158-162 11696008-2 2001 The NO donor, sodium nitroprusside (SNP), stimulated PDE5 phosphorylation and activity, which was blocked by the selective PKG inhibitor, KT5823, resulting in an elevation of cGMP levels. Cyclic GMP 175-179 phosphodiesterase 5A Homo sapiens 53-57 11696008-9 2001 Thus cGMP levels are regulated by PKG- and PKA-dependent activation of PDE5 and PKG-specific inhibition of soluble GC. Cyclic GMP 5-9 phosphodiesterase 5A Homo sapiens 71-75 11890515-6 2001 Vardenafil specifically inhibited the hydrolysis of cGMP by PDE5 with an IC50 of 0.7 nM (6.6 nM). Cyclic GMP 52-56 phosphodiesterase 5A Homo sapiens 60-64 11669467-3 2001 In this study, we compared the inhibition of cGMP hydrolysis by vardenafil and sildenafil; two inhibitors selective for phosphodiesterase type 5 (PDE5). Cyclic GMP 45-49 phosphodiesterase 5A Homo sapiens 120-144 11669467-3 2001 In this study, we compared the inhibition of cGMP hydrolysis by vardenafil and sildenafil; two inhibitors selective for phosphodiesterase type 5 (PDE5). Cyclic GMP 45-49 phosphodiesterase 5A Homo sapiens 146-150 11557915-1 2001 BACKGROUND: Sildenafil, a treatment for erectile dysfunction, is a specific phosphodiesterase type 5 (PDE 5) inhibitor that enhances nitric oxide (NO)-mediated vasodilation in the corpus cavernosum by inhibiting cyclic guanosine monophosphate breakdown. Cyclic GMP 212-242 phosphodiesterase 5A Homo sapiens 76-100 11557915-1 2001 BACKGROUND: Sildenafil, a treatment for erectile dysfunction, is a specific phosphodiesterase type 5 (PDE 5) inhibitor that enhances nitric oxide (NO)-mediated vasodilation in the corpus cavernosum by inhibiting cyclic guanosine monophosphate breakdown. Cyclic GMP 212-242 phosphodiesterase 5A Homo sapiens 102-107 11285263-5 2001 To identify the structural determinants for the inhibitory interaction with Pgamma and the remarkable cGMP hydrolytic ability, we sought to reproduce the PDE6 characteristics by mutagenesis of PDE5, a related cyclic GMP-specific, cGMP-binding PDE. Cyclic GMP 209-219 phosphodiesterase 5A Homo sapiens 193-197 11285263-5 2001 To identify the structural determinants for the inhibitory interaction with Pgamma and the remarkable cGMP hydrolytic ability, we sought to reproduce the PDE6 characteristics by mutagenesis of PDE5, a related cyclic GMP-specific, cGMP-binding PDE. Cyclic GMP 230-234 phosphodiesterase 5A Homo sapiens 193-197 11285263-6 2001 PDE5 is insensitive to Pgamma and has a more than 100-fold lower k(cat) for cGMP hydrolysis. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 0-4 11358813-8 2001 Inhibition of PDE5 appears to be pharmacologically relevant, because treatment of HT1376 cells increased cGMP and activated protein kinase G at doses that induce apoptosis, whereas cyclic AMP levels were not changed. Cyclic GMP 105-109 phosphodiesterase 5A Homo sapiens 14-18 10910034-2 2000 SW480 colon tumor cells contain guanosine 3",5"-monophosphate (cGMP) phosphodiesterase (PDE) isoforms of the PDE5 and PDE2 gene families that are inhibited by exisulind and new synthetic analogues. Cyclic GMP 32-61 phosphodiesterase 5A Homo sapiens 109-113 11289569-6 2001 Phosphodiesterase type 5 (PDE 5) is the predominant enzyme responsible for cGMP hydrolysis in trabecular smooth muscle. Cyclic GMP 75-79 phosphodiesterase 5A Homo sapiens 0-24 11289569-6 2001 Phosphodiesterase type 5 (PDE 5) is the predominant enzyme responsible for cGMP hydrolysis in trabecular smooth muscle. Cyclic GMP 75-79 phosphodiesterase 5A Homo sapiens 26-31 11289569-7 2001 Activation of PDE 5 terminates NO-induced, cGMP-mediated smooth muscle relaxation, and subsequent penile flaccidity. Cyclic GMP 43-47 phosphodiesterase 5A Homo sapiens 14-19 11137498-3 2000 Sildenafil is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Cyclic GMP 129-159 phosphodiesterase 5A Homo sapiens 50-74 11137498-3 2000 Sildenafil is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Cyclic GMP 129-159 phosphodiesterase 5A Homo sapiens 76-80 11137498-3 2000 Sildenafil is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Cyclic GMP 161-165 phosphodiesterase 5A Homo sapiens 50-74 11137498-3 2000 Sildenafil is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP). Cyclic GMP 161-165 phosphodiesterase 5A Homo sapiens 76-80 11152621-6 2000 Kinetic analyses of cGMP hydrolysis by PDE 5 showed that high concentrations of cAMP reversibly inhibited the enzyme with a K(i) of 258 +/- 54 microM. Cyclic GMP 20-24 phosphodiesterase 5A Homo sapiens 39-44 11152621-8 2000 Our data suggest that cAMP up-regulates intracellular levels of cGMP, in part, by inhibition of PDE 5. Cyclic GMP 64-68 phosphodiesterase 5A Homo sapiens 96-101 11162575-1 2001 PDE5A gene encodes type 5 phosphodiesterase (PDE5), the principal cGMP-catalyzing enzyme in the penis and the primary target of sildenafil (Viagra). Cyclic GMP 66-70 phosphodiesterase 5A Homo sapiens 0-5 11162575-1 2001 PDE5A gene encodes type 5 phosphodiesterase (PDE5), the principal cGMP-catalyzing enzyme in the penis and the primary target of sildenafil (Viagra). Cyclic GMP 66-70 phosphodiesterase 5A Homo sapiens 0-4 11162575-12 2001 Cyclic AMP and cGMP had similar stimulatory effects on the PDE5A promoter. Cyclic GMP 15-19 phosphodiesterase 5A Homo sapiens 59-64 11162576-1 2001 PDE5A gene encodes type 5 phosphodiesterase (PDE5), the principal cGMP-catalyzing enzyme in the penis and the primary target of sildenafil (Viagra). Cyclic GMP 66-70 phosphodiesterase 5A Homo sapiens 0-5 11162576-1 2001 PDE5A gene encodes type 5 phosphodiesterase (PDE5), the principal cGMP-catalyzing enzyme in the penis and the primary target of sildenafil (Viagra). Cyclic GMP 66-70 phosphodiesterase 5A Homo sapiens 0-4 10924156-2 2000 In cGMP-binding cGMP-specific PDE (PDE5), we showed previously that point mutation of nine of these profoundly decreases k(cat) when the assay is conducted in the presence of Mg(2+); seven of these are in the prototypical metal-binding motifs A and B (HX(3)HX(n)()E) that we identified earlier. Cyclic GMP 3-7 phosphodiesterase 5A Homo sapiens 30-33 10924156-2 2000 In cGMP-binding cGMP-specific PDE (PDE5), we showed previously that point mutation of nine of these profoundly decreases k(cat) when the assay is conducted in the presence of Mg(2+); seven of these are in the prototypical metal-binding motifs A and B (HX(3)HX(n)()E) that we identified earlier. Cyclic GMP 3-7 phosphodiesterase 5A Homo sapiens 35-39 10924156-2 2000 In cGMP-binding cGMP-specific PDE (PDE5), we showed previously that point mutation of nine of these profoundly decreases k(cat) when the assay is conducted in the presence of Mg(2+); seven of these are in the prototypical metal-binding motifs A and B (HX(3)HX(n)()E) that we identified earlier. Cyclic GMP 16-20 phosphodiesterase 5A Homo sapiens 30-33 10924156-2 2000 In cGMP-binding cGMP-specific PDE (PDE5), we showed previously that point mutation of nine of these profoundly decreases k(cat) when the assay is conducted in the presence of Mg(2+); seven of these are in the prototypical metal-binding motifs A and B (HX(3)HX(n)()E) that we identified earlier. Cyclic GMP 16-20 phosphodiesterase 5A Homo sapiens 35-39 10913932-7 2000 Papaverine is a non-specific inhibitor of these enzymes; sildenafil is an orally active, potent and selective inhibitor of GMP-specific PDE5, the predominant isoenzyme metabolizing cGMP in the cells of the corpus cavernosum. Cyclic GMP 181-185 phosphodiesterase 5A Homo sapiens 136-140 10977127-10 2000 Moreover, results with E4021 suggest that PDE5 activity could play a critical role in modulating cGMP-related activity in the trabecular meshwork. Cyclic GMP 97-101 phosphodiesterase 5A Homo sapiens 42-46 10910034-2 2000 SW480 colon tumor cells contain guanosine 3",5"-monophosphate (cGMP) phosphodiesterase (PDE) isoforms of the PDE5 and PDE2 gene families that are inhibited by exisulind and new synthetic analogues. Cyclic GMP 63-67 phosphodiesterase 5A Homo sapiens 109-113 10679826-0 2000 Expression and regulation of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5) in human colonic epithelial cells: role in the induction of cellular refractoriness to the heat-stable enterotoxin peptide. Cyclic GMP 33-37 phosphodiesterase 5A Homo sapiens 80-84 10769052-1 2000 We raised a polyclonal antibody against maltose binding protein fusion human cGMP-binding, cGMP-specific phosphodiesterase (PDE5) produced in E. coli. Cyclic GMP 77-81 phosphodiesterase 5A Homo sapiens 124-128 10769052-5 2000 Here we described a cell-specific localization of PDE5 in various rat tissues, suggesting the possibility of the presence of a cGMP/PDE5 pathway in these tissues. Cyclic GMP 127-131 phosphodiesterase 5A Homo sapiens 50-54 10769052-5 2000 Here we described a cell-specific localization of PDE5 in various rat tissues, suggesting the possibility of the presence of a cGMP/PDE5 pathway in these tissues. Cyclic GMP 127-131 phosphodiesterase 5A Homo sapiens 132-136 10725373-4 2000 At the N terminus PDE11A1 has a single GAF domain homologous to that found in other signaling molecules, including PDE2, PDE5, PDE6, and PDE10, which constitutes a potential allosteric binding site for cGMP or another small ligand. Cyclic GMP 202-206 phosphodiesterase 5A Homo sapiens 121-125 11228938-9 2000 Phosphodiesterase type 5 (PDE5) is responsible for the degradation of cGMP and regulation of CC muscle tone. Cyclic GMP 70-74 phosphodiesterase 5A Homo sapiens 0-24 11228938-9 2000 Phosphodiesterase type 5 (PDE5) is responsible for the degradation of cGMP and regulation of CC muscle tone. Cyclic GMP 70-74 phosphodiesterase 5A Homo sapiens 26-30 10679255-0 2000 Expression of three isoforms of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum. Cyclic GMP 32-36 phosphodiesterase 5A Homo sapiens 78-82 10679255-1 2000 Inhibition of cGMP-specific phosphodiesterase type V (PDE5) has been shown to improve penile erection in patients with erectile dysfunction. Cyclic GMP 14-18 phosphodiesterase 5A Homo sapiens 54-58 10679826-4 2000 Using the human T84 colonic cell line as a model system, we show that cGMP accumulation in these cells after ST application is regulated by the activity of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5). Cyclic GMP 70-74 phosphodiesterase 5A Homo sapiens 207-211 10679826-4 2000 Using the human T84 colonic cell line as a model system, we show that cGMP accumulation in these cells after ST application is regulated by the activity of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5). Cyclic GMP 160-164 phosphodiesterase 5A Homo sapiens 207-211 10679826-5 2000 The presence of human PDE5 in this cell line was confirmed by Western blot analysis, using an antibody raised to the bovine enzyme, and by the observation that cGMP hydrolytic activity detected in T84 cell lysates was almost completely inhibited by low concentrations of zaprinast, a specific inhibitor of PDE5. Cyclic GMP 160-164 phosphodiesterase 5A Homo sapiens 22-26 10679826-5 2000 The presence of human PDE5 in this cell line was confirmed by Western blot analysis, using an antibody raised to the bovine enzyme, and by the observation that cGMP hydrolytic activity detected in T84 cell lysates was almost completely inhibited by low concentrations of zaprinast, a specific inhibitor of PDE5. Cyclic GMP 160-164 phosphodiesterase 5A Homo sapiens 306-310 10679826-6 2000 An increase in activity of PDE5 was observed in T84 cell lysates on exposure to the ST peptide and prolonged exposure of T84 cells to the ST peptide led to the induction of cellular refractoriness in these cells, which was largely contributed in terms of an increased rate of degradation of cGMP in desensitized cells as a result of PDE5 activation. Cyclic GMP 291-295 phosphodiesterase 5A Homo sapiens 27-31 10679826-8 2000 We provide evidence for the first time that cGMP levels in the human colonocyte are regulated by the cGMP-hydrolytic activity of PDE5 and suggest that the expression and regulation of PDE5 in the intestine could therefore be important in controlling cGMP-mediated signaling in this tissue. Cyclic GMP 44-48 phosphodiesterase 5A Homo sapiens 129-133 10679826-8 2000 We provide evidence for the first time that cGMP levels in the human colonocyte are regulated by the cGMP-hydrolytic activity of PDE5 and suggest that the expression and regulation of PDE5 in the intestine could therefore be important in controlling cGMP-mediated signaling in this tissue. Cyclic GMP 44-48 phosphodiesterase 5A Homo sapiens 184-188 10679826-8 2000 We provide evidence for the first time that cGMP levels in the human colonocyte are regulated by the cGMP-hydrolytic activity of PDE5 and suggest that the expression and regulation of PDE5 in the intestine could therefore be important in controlling cGMP-mediated signaling in this tissue. Cyclic GMP 101-105 phosphodiesterase 5A Homo sapiens 129-133 10679826-8 2000 We provide evidence for the first time that cGMP levels in the human colonocyte are regulated by the cGMP-hydrolytic activity of PDE5 and suggest that the expression and regulation of PDE5 in the intestine could therefore be important in controlling cGMP-mediated signaling in this tissue. Cyclic GMP 101-105 phosphodiesterase 5A Homo sapiens 129-133 12567500-2 1999 Sildenafil is a selective inhibitor of cGMP-specific phosphodiesterase (PDE-5). Cyclic GMP 39-43 phosphodiesterase 5A Homo sapiens 72-77 10654914-1 2000 OBJECTIVES: To further investigate the mechanism of action of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase 5 (PDE5), that has been proved to be effective in the treatment of male erectile dysfunction. Cyclic GMP 99-129 phosphodiesterase 5A Homo sapiens 167-171 10654914-1 2000 OBJECTIVES: To further investigate the mechanism of action of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase 5 (PDE5), that has been proved to be effective in the treatment of male erectile dysfunction. Cyclic GMP 131-135 phosphodiesterase 5A Homo sapiens 167-171 10574925-0 1999 Expression of an active, monomeric catalytic domain of the cGMP-binding cGMP-specific phosphodiesterase (PDE5). Cyclic GMP 59-63 phosphodiesterase 5A Homo sapiens 105-109 10574925-3 1999 A deletion mutant of cGMP-binding cGMP-specific PDE (PDE5), encoding the 357 carboxyl-terminal amino acids including the catalytic domain, has been generated, expressed, and purified. Cyclic GMP 21-25 phosphodiesterase 5A Homo sapiens 53-57 10574925-3 1999 A deletion mutant of cGMP-binding cGMP-specific PDE (PDE5), encoding the 357 carboxyl-terminal amino acids including the catalytic domain, has been generated, expressed, and purified. Cyclic GMP 34-38 phosphodiesterase 5A Homo sapiens 53-57 12567500-4 1999 The biological actions of cGMP are terminated by phosphodiesterase enzymes and PDE-5 is the major cGMP metabolising enzyme in this tissue. Cyclic GMP 26-30 phosphodiesterase 5A Homo sapiens 79-84 12567500-4 1999 The biological actions of cGMP are terminated by phosphodiesterase enzymes and PDE-5 is the major cGMP metabolising enzyme in this tissue. Cyclic GMP 98-102 phosphodiesterase 5A Homo sapiens 79-84 10506154-0 1999 Studies of the molecular mechanism of discrimination between cGMP and cAMP in the allosteric sites of the cGMP-binding cGMP-specific phosphodiesterase (PDE5). Cyclic GMP 106-110 phosphodiesterase 5A Homo sapiens 152-156 10506154-0 1999 Studies of the molecular mechanism of discrimination between cGMP and cAMP in the allosteric sites of the cGMP-binding cGMP-specific phosphodiesterase (PDE5). Cyclic GMP 61-65 phosphodiesterase 5A Homo sapiens 152-156 10506154-1 1999 The regulatory domain of the cGMP-binding cGMP-specific 3":5"-cyclic nucleotide phosphodiesterase (PDE5) contains two homologous segments of amino acid sequence that encode allosteric cyclic nucleotide-binding sites, referred to as site a and site b, which are highly selective for cGMP over cAMP. Cyclic GMP 29-33 phosphodiesterase 5A Homo sapiens 99-103 10506154-4 1999 The total cGMP binding by PDE5 was unchanged by variation in pH, but the relative affinity for cGMP versus cAMP progressively decreased as the pH was lowered. Cyclic GMP 10-14 phosphodiesterase 5A Homo sapiens 26-30 10506154-4 1999 The total cGMP binding by PDE5 was unchanged by variation in pH, but the relative affinity for cGMP versus cAMP progressively decreased as the pH was lowered. Cyclic GMP 95-99 phosphodiesterase 5A Homo sapiens 26-30 12973386-5 1999 Sildenafil causes an erection by inhibiting PDE5, which in turn causes an increase in the intracellular levels of cGMP. Cyclic GMP 114-118 phosphodiesterase 5A Homo sapiens 44-48 10385692-1 1999 The cGMP-binding cGMP-specific phosphodiesterase (PDE5) degrades cGMP and regulates the intracellular level of cGMP in many tissues, including the smooth muscle of the corpus cavernosum of the penis. Cyclic GMP 4-8 phosphodiesterase 5A Homo sapiens 50-54 10385692-1 1999 The cGMP-binding cGMP-specific phosphodiesterase (PDE5) degrades cGMP and regulates the intracellular level of cGMP in many tissues, including the smooth muscle of the corpus cavernosum of the penis. Cyclic GMP 17-21 phosphodiesterase 5A Homo sapiens 50-54 10385692-1 1999 The cGMP-binding cGMP-specific phosphodiesterase (PDE5) degrades cGMP and regulates the intracellular level of cGMP in many tissues, including the smooth muscle of the corpus cavernosum of the penis. Cyclic GMP 17-21 phosphodiesterase 5A Homo sapiens 50-54 10385692-1 1999 The cGMP-binding cGMP-specific phosphodiesterase (PDE5) degrades cGMP and regulates the intracellular level of cGMP in many tissues, including the smooth muscle of the corpus cavernosum of the penis. Cyclic GMP 17-21 phosphodiesterase 5A Homo sapiens 50-54 10385692-2 1999 Sildenafil (Viagra), a specific PDE5 inhibitor, promotes penile erection by blocking the activity of PDE5, which causes cGMP to accumulate in the corpus cavernosum. Cyclic GMP 120-124 phosphodiesterase 5A Homo sapiens 101-105 10385692-3 1999 In the present study, sildenafil, like other PDE5 inhibitors, stimulates cGMP binding to the allosteric sites of PDE5 by interacting at the catalytic site of this enzyme, but the drug does not compete with cGMP for binding at the allosteric sites. Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 113-117 10385692-8 1999 The affinity of each of these inhibitors for PDE5 is much higher than that of cGMP itself (Km = 2000 nM). Cyclic GMP 78-82 phosphodiesterase 5A Homo sapiens 45-49 10078538-2 1999 Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in men with erectile dysfunction. Cyclic GMP 168-172 phosphodiesterase 5A Homo sapiens 39-63 10078538-2 1999 Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in men with erectile dysfunction. Cyclic GMP 168-172 phosphodiesterase 5A Homo sapiens 65-69 10078539-1 1999 Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. Cyclic GMP 37-67 phosphodiesterase 5A Homo sapiens 110-114 10078539-1 1999 Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. Cyclic GMP 69-73 phosphodiesterase 5A Homo sapiens 110-114 10078537-2 1999 Its action results from increased levels of cyclic guanosine monophosphate (cGMP), which is normally degraded by PDE5. Cyclic GMP 44-74 phosphodiesterase 5A Homo sapiens 113-117 10078537-2 1999 Its action results from increased levels of cyclic guanosine monophosphate (cGMP), which is normally degraded by PDE5. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 113-117 9817684-2 1998 Dipyridamole, a drug with several putative vasodilator mechanisms, is an inhibitor of cGMP-specific phosphodiesterases (PDE5); it therefore has the potential to increase pulmonary vascular cGMP levels, lower pulmonary vascular resistance, augment iNO-induced pulmonary vasodilation, and attenuate excessive pulmonary vasoreactivity. Cyclic GMP 86-90 phosphodiesterase 5A Homo sapiens 120-124 9922221-9 1999 Increased cyclic guanosine monophosphate levels in these cells provoked by sodium nitroprusside and the PDE5 inhibitor zaprinast reduced the PGE2 synthesis, whereas 15-HETE and IL-8 formation were unchanged. Cyclic GMP 10-40 phosphodiesterase 5A Homo sapiens 104-108 9817684-2 1998 Dipyridamole, a drug with several putative vasodilator mechanisms, is an inhibitor of cGMP-specific phosphodiesterases (PDE5); it therefore has the potential to increase pulmonary vascular cGMP levels, lower pulmonary vascular resistance, augment iNO-induced pulmonary vasodilation, and attenuate excessive pulmonary vasoreactivity. Cyclic GMP 189-193 phosphodiesterase 5A Homo sapiens 120-124 9642111-0 1998 Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase (PDE5). Cyclic GMP 42-46 phosphodiesterase 5A Homo sapiens 88-92 9916601-1 1998 Sildenafil citrate, an oral therapy for erectile dysfunction, is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), the predominant isozyme metabolizing cGMP in the corpus cavernosum. Cyclic GMP 90-120 phosphodiesterase 5A Homo sapiens 163-167 9916601-1 1998 Sildenafil citrate, an oral therapy for erectile dysfunction, is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), the predominant isozyme metabolizing cGMP in the corpus cavernosum. Cyclic GMP 207-211 phosphodiesterase 5A Homo sapiens 163-167 9916601-3 1998 Sildenafil has no direct relaxant effect on human corpus cavernosum but enhances the relaxant effect of nitric oxide (NO) on the corpus cavernosum by inhibiting PDE5, which is responsible for degradation of cGMP in this tissue. Cyclic GMP 207-211 phosphodiesterase 5A Homo sapiens 161-165 9916601-4 1998 When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil increases concentrations of cGMP in the corpus cavernosum, causing smooth muscle relaxation and blood flow into the penis, resulting in an erection. Cyclic GMP 113-117 phosphodiesterase 5A Homo sapiens 66-70 9765278-13 1998 In summary, inhibitors of either GC or PDE5 prevented IL-1 induction of iNOS; IL-1 increased the rates of both cGMP generation and hydrolysis; and exogenous PDE hydrolyzable cGMP analog induced iNOS and NO. Cyclic GMP 174-178 phosphodiesterase 5A Homo sapiens 39-43 9765278-14 1998 These results suggest that increased cGMP metabolic flux is sufficient to induce iNOS, and GC and PDE5 activities are required for IL-1 induction of iNOS expression via increases in coupled cGMP synthesis and hydrolysis. Cyclic GMP 190-194 phosphodiesterase 5A Homo sapiens 98-102 9716380-0 1998 Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene. Cyclic GMP 64-68 phosphodiesterase 5A Homo sapiens 109-114 9716380-0 1998 Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene. Cyclic GMP 77-81 phosphodiesterase 5A Homo sapiens 109-114 9716380-1 1998 cGMP-binding, cGMP-specific phosphodiesterase which is encoded by the PDE5A gene plays important roles in cardiovascular system, and is a significant target molecule of therapeutic agents. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 70-75 9716380-1 1998 cGMP-binding, cGMP-specific phosphodiesterase which is encoded by the PDE5A gene plays important roles in cardiovascular system, and is a significant target molecule of therapeutic agents. Cyclic GMP 14-18 phosphodiesterase 5A Homo sapiens 70-75 9624146-12 1998 PDE9A lacks a region homologous to the allosteric cGMP-binding regulatory regions found in the cGMP-binding PDEs: PDE2, PDE5, and PDE6. Cyclic GMP 50-54 phosphodiesterase 5A Homo sapiens 120-124 9624146-12 1998 PDE9A lacks a region homologous to the allosteric cGMP-binding regulatory regions found in the cGMP-binding PDEs: PDE2, PDE5, and PDE6. Cyclic GMP 95-99 phosphodiesterase 5A Homo sapiens 120-124 9642111-1 1998 A human PDE5 cDNA has been isolated which contains an open reading frame encoding an 875 amino acid, 100,012 Da polypeptide, the expression of which yields a protein of the predicted size and is capable of hydrolyzing cGMP. Cyclic GMP 218-222 phosphodiesterase 5A Homo sapiens 8-12 9642111-2 1998 The deduced amino acid sequence is very similar (95%) to that of bovine PDE5, and comprises a conserved cGMP-binding domain and catalytic domain. Cyclic GMP 104-108 phosphodiesterase 5A Homo sapiens 72-76 9445376-8 1998 It is concluded that cGMP binding to the allosteric sites of cGB-PDE does not directly affect catalysis, but binding to both of these sites regulates phosphorylation of this enzyme. Cyclic GMP 21-25 phosphodiesterase 5A Homo sapiens 61-68 9486247-1 1998 Guanosine 3",5"-cyclic monophosphate (cGMP)-binding, cGMP-specific phosphodiesterase (PDE5) is abundant in vascular smooth muscle, and this enzyme is a potent substrate for cGMP-dependent protein kinase (PKG) in vitro. Cyclic GMP 0-36 phosphodiesterase 5A Homo sapiens 86-90 9486247-1 1998 Guanosine 3",5"-cyclic monophosphate (cGMP)-binding, cGMP-specific phosphodiesterase (PDE5) is abundant in vascular smooth muscle, and this enzyme is a potent substrate for cGMP-dependent protein kinase (PKG) in vitro. Cyclic GMP 38-42 phosphodiesterase 5A Homo sapiens 86-90 9486247-2 1998 Binding of cGMP to the allosteric sites of PDE5 is required for this phosphorylation to occur. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 43-47 9486247-3 1998 Vascular smooth muscle cells (VSMC) were used to determine if PDE5 is phosphorylated in intact cells when cGMP is increased. Cyclic GMP 106-110 phosphodiesterase 5A Homo sapiens 62-66 9486247-10 1998 However, incubation of immunoprecipitated PDE5 from these cells with purified PKG, cGMP, and a phosphorylation mixture containing [gamma-32P]ATP resulted in 32(Pi) incorporation into PDE5 that was correlated with increased catalytic activity. Cyclic GMP 83-87 phosphodiesterase 5A Homo sapiens 42-46 9486247-10 1998 However, incubation of immunoprecipitated PDE5 from these cells with purified PKG, cGMP, and a phosphorylation mixture containing [gamma-32P]ATP resulted in 32(Pi) incorporation into PDE5 that was correlated with increased catalytic activity. Cyclic GMP 83-87 phosphodiesterase 5A Homo sapiens 183-187 9445376-0 1998 Binding of cGMP to both allosteric sites of cGMP-binding cGMP-specific phosphodiesterase (PDE5) is required for its phosphorylation. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 44-88 9445376-0 1998 Binding of cGMP to both allosteric sites of cGMP-binding cGMP-specific phosphodiesterase (PDE5) is required for its phosphorylation. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 90-94 9445376-3 1998 The cGMP-binding sites of one of these phosphodiesterases, the cGMP-binding cGMP-specific phosphodiesterase (cGB-PDE, PDE5), have been analysed by using site-directed mutagenesis. Cyclic GMP 4-8 phosphodiesterase 5A Homo sapiens 63-107 9445376-3 1998 The cGMP-binding sites of one of these phosphodiesterases, the cGMP-binding cGMP-specific phosphodiesterase (cGB-PDE, PDE5), have been analysed by using site-directed mutagenesis. Cyclic GMP 4-8 phosphodiesterase 5A Homo sapiens 109-116 9445376-3 1998 The cGMP-binding sites of one of these phosphodiesterases, the cGMP-binding cGMP-specific phosphodiesterase (cGB-PDE, PDE5), have been analysed by using site-directed mutagenesis. Cyclic GMP 4-8 phosphodiesterase 5A Homo sapiens 118-122 9445376-6 1998 The cGMP effect is on the cGB-PDE rather than on the catalytic subunit of the protein kinase because the latter enzyme does not require cGMP for activity. Cyclic GMP 4-8 phosphodiesterase 5A Homo sapiens 26-33 9218482-4 1997 The type 5 phosphodiesterase (PDE-5) isoform shares a number of similar characteristics with PDE-6, including binding of cGMP to noncatalytic sites, the cyclic nucleotide specificity, and inhibitor sensitivities. Cyclic GMP 121-125 phosphodiesterase 5A Homo sapiens 30-35 34875337-1 2022 Type 5 phosphodiesterase (PDE5) blockade by inhibitors (PDE5i) results in intracellular cyclic guanosine monophosphate (cGMP) increase and smooth muscle relaxation and are used for the treatment of men erectile dysfunction. Cyclic GMP 88-118 phosphodiesterase 5A Homo sapiens 26-30 7870041-7 1995 PDE3 and PDE5 have reduced apparent affinity for these analogs and therefore either are sterically hindered with these substitutions or bind cGMP in the anti-conformation. Cyclic GMP 141-145 phosphodiesterase 5A Homo sapiens 9-13 8226796-9 1993 The sequence of cGB-PDE contained a segment (AA 578-812) that was homologous to the putative catalytic region conserved among all mammalian PDEs and a segment (AA 142-526) that was homologous to the putative cGMP binding region of the cGMP-stimulated PDE and the photoreceptor PDEs. Cyclic GMP 208-212 phosphodiesterase 5A Homo sapiens 16-23 8226796-9 1993 The sequence of cGB-PDE contained a segment (AA 578-812) that was homologous to the putative catalytic region conserved among all mammalian PDEs and a segment (AA 142-526) that was homologous to the putative cGMP binding region of the cGMP-stimulated PDE and the photoreceptor PDEs. Cyclic GMP 235-239 phosphodiesterase 5A Homo sapiens 16-23 33809319-1 2021 Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. Cyclic GMP 165-195 phosphodiesterase 5A Homo sapiens 0-24 33809319-1 2021 Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. Cyclic GMP 165-195 phosphodiesterase 5A Homo sapiens 26-30 33809319-1 2021 Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. Cyclic GMP 197-201 phosphodiesterase 5A Homo sapiens 0-24 33809319-1 2021 Phosphodiesterase type 5 (PDE5) inhibitors such as Viagra (sildenafil citrate) have demonstrated efficacy in the treatment of erectile dysfunction (ED) by inducing cyclic guanosine monophosphate (cGMP) elevation followed by vasodilation and increased blood flow. Cyclic GMP 197-201 phosphodiesterase 5A Homo sapiens 26-30 9115850-2 1996 In human platelets, the cGMP-hydrolytic activity was about six times higher than the cAMP-hydrolytic activity, and PDE5 and PDE3 are the major phosphodiesterase isoenzymes that hydrolyze cGMP and cAMP, respectively. Cyclic GMP 187-191 phosphodiesterase 5A Homo sapiens 115-119 7653611-2 1995 Because cGMP is hydrolyzed and inactivated by phosphodiesterase enzymes, we evaluated the hemodynamic effects of two cGMP-specific phosphodiesterase (PDE5) inhibitors, dipyridamole and zaprinast, in the near-term chronically prepared ovine fetus. Cyclic GMP 117-121 phosphodiesterase 5A Homo sapiens 150-154 26410556-6 2015 Moreover, potential synergisms of BAY 41-2272 or BAY 60-2770 and inhibition of cGMP degradation by the PDE5 inhibitor vardenafil were investigated. Cyclic GMP 79-83 phosphodiesterase 5A Homo sapiens 103-107 26253809-1 2015 Sildenafil is a selective inhibitor of cGMP-specific type 5 phosphodiesterase (PDE5) used for the treatment of masculine erectile dysfunction and Pulmonary Arterial Hypertension (PAH). Cyclic GMP 39-43 phosphodiesterase 5A Homo sapiens 79-83 34875337-1 2022 Type 5 phosphodiesterase (PDE5) blockade by inhibitors (PDE5i) results in intracellular cyclic guanosine monophosphate (cGMP) increase and smooth muscle relaxation and are used for the treatment of men erectile dysfunction. Cyclic GMP 120-124 phosphodiesterase 5A Homo sapiens 26-30 34471776-2 2021 Such agents would improve our understanding of the nitric oxide (NO)/cyclic guanosine 3",5"-monophosphate (cGMP)/PDE5 pathway in human pathologies and potentially lead to novel uses of PDE5 inhibitors to manage lung conditions like SARS-CoV-2-mediated pulmonary inflammatory responses. Cyclic GMP 69-105 phosphodiesterase 5A Homo sapiens 113-117 34727793-1 2021 Phosphodiesterase 5 (PDE5) falls under a broad category of metallohydrolase enzymes responsible for the catalysis of the phosphodiesterase bond, and thus it can terminate the action of cyclic guanosine monophosphate (cGMP). Cyclic GMP 185-215 phosphodiesterase 5A Homo sapiens 0-19 34727793-1 2021 Phosphodiesterase 5 (PDE5) falls under a broad category of metallohydrolase enzymes responsible for the catalysis of the phosphodiesterase bond, and thus it can terminate the action of cyclic guanosine monophosphate (cGMP). Cyclic GMP 185-215 phosphodiesterase 5A Homo sapiens 21-25 34727793-1 2021 Phosphodiesterase 5 (PDE5) falls under a broad category of metallohydrolase enzymes responsible for the catalysis of the phosphodiesterase bond, and thus it can terminate the action of cyclic guanosine monophosphate (cGMP). Cyclic GMP 217-221 phosphodiesterase 5A Homo sapiens 0-19 34727793-1 2021 Phosphodiesterase 5 (PDE5) falls under a broad category of metallohydrolase enzymes responsible for the catalysis of the phosphodiesterase bond, and thus it can terminate the action of cyclic guanosine monophosphate (cGMP). Cyclic GMP 217-221 phosphodiesterase 5A Homo sapiens 21-25 34507030-4 2021 The main enzyme responsible for the degradation of cGMP is PDE5. Cyclic GMP 51-55 phosphodiesterase 5A Homo sapiens 59-63 34638713-2 2021 In a cirrhotic liver, the key enzymes endothelial NO synthase (eNOS), soluble guanylate cyclase (sGC), and phosphodiesterase-5 (PDE-5) are overexpressed, leading to decreased cyclic guanosine-monophosphate (cGMP). Cyclic GMP 175-205 phosphodiesterase 5A Homo sapiens 107-126 34638713-2 2021 In a cirrhotic liver, the key enzymes endothelial NO synthase (eNOS), soluble guanylate cyclase (sGC), and phosphodiesterase-5 (PDE-5) are overexpressed, leading to decreased cyclic guanosine-monophosphate (cGMP). Cyclic GMP 175-205 phosphodiesterase 5A Homo sapiens 128-133 34638713-2 2021 In a cirrhotic liver, the key enzymes endothelial NO synthase (eNOS), soluble guanylate cyclase (sGC), and phosphodiesterase-5 (PDE-5) are overexpressed, leading to decreased cyclic guanosine-monophosphate (cGMP). Cyclic GMP 207-211 phosphodiesterase 5A Homo sapiens 107-126 34638713-2 2021 In a cirrhotic liver, the key enzymes endothelial NO synthase (eNOS), soluble guanylate cyclase (sGC), and phosphodiesterase-5 (PDE-5) are overexpressed, leading to decreased cyclic guanosine-monophosphate (cGMP). Cyclic GMP 207-211 phosphodiesterase 5A Homo sapiens 128-133 34638713-8 2021 Preclinical and clinical data have demonstrated that targeting the NO-cGMP pathway in liver cirrhosis using PDE-5 inhibitors or sGC stimulators/activators decreases intrahepatic resistance through dilation of sinusoids, lowering portal pressure, and increasing portal venous blood flow. Cyclic GMP 70-74 phosphodiesterase 5A Homo sapiens 108-113 34820318-1 2021 Sildenafil is a specific inhibitor of the phosphodiesterase type 5 (PDE-5) enzyme that protects cyclic guanosine monophosphate from breakdown by PDE-5. Cyclic GMP 96-126 phosphodiesterase 5A Homo sapiens 42-66 34820318-1 2021 Sildenafil is a specific inhibitor of the phosphodiesterase type 5 (PDE-5) enzyme that protects cyclic guanosine monophosphate from breakdown by PDE-5. Cyclic GMP 96-126 phosphodiesterase 5A Homo sapiens 68-73 34820318-1 2021 Sildenafil is a specific inhibitor of the phosphodiesterase type 5 (PDE-5) enzyme that protects cyclic guanosine monophosphate from breakdown by PDE-5. Cyclic GMP 96-126 phosphodiesterase 5A Homo sapiens 145-150 34471776-2 2021 Such agents would improve our understanding of the nitric oxide (NO)/cyclic guanosine 3",5"-monophosphate (cGMP)/PDE5 pathway in human pathologies and potentially lead to novel uses of PDE5 inhibitors to manage lung conditions like SARS-CoV-2-mediated pulmonary inflammatory responses. Cyclic GMP 69-105 phosphodiesterase 5A Homo sapiens 185-189 34471776-2 2021 Such agents would improve our understanding of the nitric oxide (NO)/cyclic guanosine 3",5"-monophosphate (cGMP)/PDE5 pathway in human pathologies and potentially lead to novel uses of PDE5 inhibitors to manage lung conditions like SARS-CoV-2-mediated pulmonary inflammatory responses. Cyclic GMP 107-111 phosphodiesterase 5A Homo sapiens 113-117 34471575-4 2021 Phosphodiesterase-5 (PDE-5) inhibitors act on nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) and are an effective treatment option in some CPP syndromes. Cyclic GMP 68-98 phosphodiesterase 5A Homo sapiens 0-19 34393818-0 2021 Treatment of Cardiovascular Dysfunction With PDE5-Inhibitors - Temperature Dependent Effects on Transport and Metabolism of cAMP and cGMP. Cyclic GMP 133-137 phosphodiesterase 5A Homo sapiens 45-49 34471575-4 2021 Phosphodiesterase-5 (PDE-5) inhibitors act on nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) and are an effective treatment option in some CPP syndromes. Cyclic GMP 68-98 phosphodiesterase 5A Homo sapiens 21-26 34471575-4 2021 Phosphodiesterase-5 (PDE-5) inhibitors act on nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) and are an effective treatment option in some CPP syndromes. Cyclic GMP 100-104 phosphodiesterase 5A Homo sapiens 0-19 34471575-4 2021 Phosphodiesterase-5 (PDE-5) inhibitors act on nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) and are an effective treatment option in some CPP syndromes. Cyclic GMP 100-104 phosphodiesterase 5A Homo sapiens 21-26 35050491-5 2022 However, contradictory reports have suggested a pro-oncogenic role for neuronal cyclic guanosine monophosphate (cGMP), indicating the beneficial function of PDE5 in the brain of GBM patients. Cyclic GMP 80-110 phosphodiesterase 5A Homo sapiens 157-161 34175342-1 2022 Sildenafil citrate is a selective oral phosphodiesterase 5 (PDE5) inhibitor, a widely used drug for erectile dysfunction that acts by elevating cGMP levels and causing smooth muscle relaxation. Cyclic GMP 144-148 phosphodiesterase 5A Homo sapiens 60-64 35050491-5 2022 However, contradictory reports have suggested a pro-oncogenic role for neuronal cyclic guanosine monophosphate (cGMP), indicating the beneficial function of PDE5 in the brain of GBM patients. Cyclic GMP 112-116 phosphodiesterase 5A Homo sapiens 157-161 35369720-8 2022 PDE5A have bioactivity with the amino acid residues (Val230, Asn252, Gln133 and Thr166) throughout PDE5A-cGMP-PKG pathways which involved reduction in myofilament responsiveness. Cyclic GMP 105-109 phosphodiesterase 5A Homo sapiens 0-5 34984916-1 2022 Background cGMP-hydrolyzing phosphodiesterase type 5 (PDE5) regulates vascular smooth muscle cell (SMC) contraction by antagonizing cGMP-dependent protein kinase I (PKGI)-dependent SMC relaxation. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 54-58 35163827-4 2022 This BRET variant, called CYGYEL (cyclic GMP sensor using YFP-PDE5-Rluc8), was cloned into a lentiviral vector for use across different mammalian cell types. Cyclic GMP 34-44 phosphodiesterase 5A Homo sapiens 62-66 35119252-4 2022 The phosphodiesterase type 5 (PDE5) is the enzyme engaged to hydrolyze cGMP in inactive 5"- GMP form. Cyclic GMP 71-75 phosphodiesterase 5A Homo sapiens 30-34 35369720-8 2022 PDE5A have bioactivity with the amino acid residues (Val230, Asn252, Gln133 and Thr166) throughout PDE5A-cGMP-PKG pathways which involved reduction in myofilament responsiveness. Cyclic GMP 105-109 phosphodiesterase 5A Homo sapiens 99-104 33741394-10 2021 On a molecular level, PDE5 inhibition downregulates BZLF1 and BRLF1 through cGMP/PKG signaling-induced ZNF overexpression. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 22-26 33348311-1 2021 Phosphodiesterase 5 (PDE5) is one of the most well-studied phosphodiesterases (PDEs) that specifically targets cGMP typically generated by nitric oxide (NO)-mediated activation of the soluble guanylyl cyclase. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 0-19 33718200-5 2021 Sildenafil, tadalafil, and vardenafil are PDE5 inhibitors and potent vasodilators, that extend the physiological effects of nitric oxide and cyclic guanosine monophosphate (cGMP) signaling. Cyclic GMP 141-171 phosphodiesterase 5A Homo sapiens 42-46 33718200-5 2021 Sildenafil, tadalafil, and vardenafil are PDE5 inhibitors and potent vasodilators, that extend the physiological effects of nitric oxide and cyclic guanosine monophosphate (cGMP) signaling. Cyclic GMP 173-177 phosphodiesterase 5A Homo sapiens 42-46 33572094-3 2021 The PDE5 inhibitors prevent the degradation of cyclic guanosine monophosphate, thereby causing severe hypotension as a marked side effect. Cyclic GMP 47-77 phosphodiesterase 5A Homo sapiens 4-8 33348311-1 2021 Phosphodiesterase 5 (PDE5) is one of the most well-studied phosphodiesterases (PDEs) that specifically targets cGMP typically generated by nitric oxide (NO)-mediated activation of the soluble guanylyl cyclase. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 21-25 33348311-2 2021 Given the crucial role of cGMP generated through the activation of this cellular signaling pathway in a variety of physiologically processes, pharmacological inhibition of PDE5 has been demonstrated to have several therapeutic applications including erectile dysfunction and pulmonary arterial hypertension. Cyclic GMP 26-30 phosphodiesterase 5A Homo sapiens 172-176 32526061-0 2021 Targeting the NO-cGMP-PDE5 pathway in COVID-19 infection. Cyclic GMP 17-21 phosphodiesterase 5A Homo sapiens 22-26 32526061-9 2021 MATERIALS AND METHODS: We performed a systematic review of all evidence documenting any involvement of the NO-cGMP-PDE5 axis in the pathophysiology of COVID-19, presenting the ongoing clinical trials aimed at modulating this axis, including our own "silDEnafil administration in DiAbetic and dysmetaboLic patients with COVID-19 (DEDALO trial)." Cyclic GMP 110-114 phosphodiesterase 5A Homo sapiens 115-119 32872119-4 2020 Vascular tone is primarily regulated by the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, wherein soluble guanylate cyclase (sGC) and phosphodiesterase-5 (PDE-5) are key enzymes. Cyclic GMP 57-87 phosphodiesterase 5A Homo sapiens 151-170 32534033-3 2020 In contrast, drugs increasing cGMP by inhibiting phosphodiesterase 5 (PDE-5) are well tolerated in children with pulmonary hypertension. Cyclic GMP 30-34 phosphodiesterase 5A Homo sapiens 49-68 32534033-3 2020 In contrast, drugs increasing cGMP by inhibiting phosphodiesterase 5 (PDE-5) are well tolerated in children with pulmonary hypertension. Cyclic GMP 30-34 phosphodiesterase 5A Homo sapiens 70-75 32628940-3 2020 This review aims at providing an overview on the role of PDE5, the cGMP-specific phosphodiesterase that historically attracted much attention for its involvement in male impotence, in the regulation of vascular smooth muscle cell function. Cyclic GMP 67-71 phosphodiesterase 5A Homo sapiens 57-61 32454444-1 2020 Widespread cGMP-specific phosphodiesterase 5 (PDE5) inhibitor use in male reproductive health and particularly in prostate cancer patients following surgery has generated interest in how these drugs affect the ability of residual tumor cells to proliferate, migrate, and form recurrent colonies. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 46-50 32454444-3 2020 Proliferation, colony formation, and migration phenotypes remained stable even when cells were co-treated with a stimulator of cGMP synthesis that facilitated cGMP accumulation upon PDE5 inhibition. Cyclic GMP 127-131 phosphodiesterase 5A Homo sapiens 182-186 32454444-3 2020 Proliferation, colony formation, and migration phenotypes remained stable even when cells were co-treated with a stimulator of cGMP synthesis that facilitated cGMP accumulation upon PDE5 inhibition. Cyclic GMP 159-163 phosphodiesterase 5A Homo sapiens 182-186 32964819-3 2021 The enzyme phosphodiesterase type 5 (PDE5) curtails the actions of cGMP by hydrolyzing it into inactive 5"-GMP. Cyclic GMP 67-71 phosphodiesterase 5A Homo sapiens 11-35 32964819-3 2021 The enzyme phosphodiesterase type 5 (PDE5) curtails the actions of cGMP by hydrolyzing it into inactive 5"-GMP. Cyclic GMP 67-71 phosphodiesterase 5A Homo sapiens 37-41 32964819-4 2021 Small molecule PDE5 inhibitors (PDE5is) such as sildenafil prolong the availability of cGMP and so enhance NO-mediated signalling. Cyclic GMP 87-91 phosphodiesterase 5A Homo sapiens 15-19 32964819-4 2021 Small molecule PDE5 inhibitors (PDE5is) such as sildenafil prolong the availability of cGMP and so enhance NO-mediated signalling. Cyclic GMP 87-91 phosphodiesterase 5A Homo sapiens 32-36 32872119-4 2020 Vascular tone is primarily regulated by the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, wherein soluble guanylate cyclase (sGC) and phosphodiesterase-5 (PDE-5) are key enzymes. Cyclic GMP 57-87 phosphodiesterase 5A Homo sapiens 172-177 32872119-7 2020 This review describes current knowledge of the pathophysiology of PH with focus on the enzymes regulating cGMP availability, i.e., sGC and PDE-5. Cyclic GMP 106-110 phosphodiesterase 5A Homo sapiens 139-144 32562844-0 2020 PDE5 and PDE10 inhibition activates cGMP/PKG signaling to block Wnt/beta-catenin transcription, cancer cell growth, and tumor immunity. Cyclic GMP 36-40 phosphodiesterase 5A Homo sapiens 0-4 32562844-4 2020 In this review, we describe the rationale for using the sulindac scaffold to design-out COX inhibitory activity, while improving potency and selectivity to inhibit PDE5 and PDE10 that activate cGMP/PKG signaling to suppress Wnt/beta-catenin transcription, cancer cell growth, and tumor immunity. Cyclic GMP 193-197 phosphodiesterase 5A Homo sapiens 164-168 32229414-3 2020 PDE5 inhibitors prevent both cellular metabolism and cGMP efflux by inhibiting ABCC5 as well as PDE5. Cyclic GMP 53-57 phosphodiesterase 5A Homo sapiens 0-4 32229414-3 2020 PDE5 inhibitors prevent both cellular metabolism and cGMP efflux by inhibiting ABCC5 as well as PDE5. Cyclic GMP 53-57 phosphodiesterase 5A Homo sapiens 96-100 32191546-5 2020 We discuss the consequences of downregulated cGMP-dependent phosphodiesterase type 5 (PDE5) activity in response to these molecular signaling derangements, as the main effector mechanism causing unrestrained cavernous tissue relaxation that results in priapism.Expert opinion: Basic science studies are crucial for understanding the underlying pathophysiology of SCD-associated priapism. Cyclic GMP 45-49 phosphodiesterase 5A Homo sapiens 86-90 32231130-0 2020 Burn-Induced Cardiac Mitochondrial Dysfunction via Interruption of the PDE5A-cGMP-PKG Pathway. Cyclic GMP 77-81 phosphodiesterase 5A Homo sapiens 71-76 32467879-1 2020 Nitric oxide/cyclic guanosine monophosphate (cGMP) signaling is compromised in Alzheimer"s disease (AD), and phosphodiesterase 5 (PDE5), which degrades cGMP, is upregulated. Cyclic GMP 152-156 phosphodiesterase 5A Homo sapiens 109-128 32467879-1 2020 Nitric oxide/cyclic guanosine monophosphate (cGMP) signaling is compromised in Alzheimer"s disease (AD), and phosphodiesterase 5 (PDE5), which degrades cGMP, is upregulated. Cyclic GMP 152-156 phosphodiesterase 5A Homo sapiens 130-134 32231130-3 2020 This study sought to understand whether burn-induced heart dysfunction is associated with cardiac mitochondrial dysfunction and interruption of the PDE5A-cGMP-PKG pathway. Cyclic GMP 154-158 phosphodiesterase 5A Homo sapiens 148-153 32231130-11 2020 Sildenafil, a inhibitor of the PDE5A-cGMP-PKG pathway, preserved the mitochondrial structure, respiratory chain efficiency and energy status in cardiac tissue. Cyclic GMP 37-41 phosphodiesterase 5A Homo sapiens 31-36 32231130-13 2020 In conclusion, cardiac mitochondrial damage contributes to burn-induced heart dysfunction via the PDE5A-cGMP-PKG pathway. Cyclic GMP 104-108 phosphodiesterase 5A Homo sapiens 98-103 32427079-8 2020 This should increase cyclic guanosine-monophosphate (cGMP) generation and inhibit phosphodiesterases (specially PDE5) that selectively degrade cGMP. Cyclic GMP 143-147 phosphodiesterase 5A Homo sapiens 112-116 32215350-0 2020 Estrogen Receptor-alpha Non-Nuclear Signaling Confers Cardioprotection and Is Essential to cGMP-PDE5 Inhibition Efficacy. Cyclic GMP 91-95 phosphodiesterase 5A Homo sapiens 96-100 30388886-0 2019 Hydroalcoholic Extract of Levisticum officinale Increases cGMP Signaling Pathway by Down-Regulating PDE5 Expression and Induction of Apoptosis in MCF-7 and MDA-MB-468 Breast Cancer Cell Lines Background: This study aimed to investigate Levisticum officinale hydroalcoholic extract (LOHE) effect on both cGMP signaling pathway and phosphodiesterase 5 (PDE5) gene expression pattern and to examine the role of LOHE in apoptosis induction of MCF-7 and MDA-MB-468 cell lines. Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 100-104 31248451-12 2019 Pharmacological inhibition of cGMP degradation through inhibition of phosphodiesterase 5 (PDE5), rescued oTau-induced LTP reduction. Cyclic GMP 30-34 phosphodiesterase 5A Homo sapiens 69-88 31248451-12 2019 Pharmacological inhibition of cGMP degradation through inhibition of phosphodiesterase 5 (PDE5), rescued oTau-induced LTP reduction. Cyclic GMP 30-34 phosphodiesterase 5A Homo sapiens 90-94 31248451-14 2019 Finally, PDE5 inhibition re-established normal elevation of CREB phosphorylation and cGMP levels after memory induction in the presence of oTau. Cyclic GMP 85-89 phosphodiesterase 5A Homo sapiens 9-13 30350485-8 2019 Nonetheless, the substantial evidence implicating PDE5 inhibition in the cyclic guanosine monophosphate (cGMP)-mediated melanoma pathway warrants further investigation in the clinical setting. Cyclic GMP 73-103 phosphodiesterase 5A Homo sapiens 50-54 30350485-8 2019 Nonetheless, the substantial evidence implicating PDE5 inhibition in the cyclic guanosine monophosphate (cGMP)-mediated melanoma pathway warrants further investigation in the clinical setting. Cyclic GMP 105-109 phosphodiesterase 5A Homo sapiens 50-54 31434939-3 2019 We analyzed the mRNA levels of PDE5, a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs, that regulates arterious vascular tone by lowering cGMP levels. Cyclic GMP 39-43 phosphodiesterase 5A Homo sapiens 31-35 31434939-3 2019 We analyzed the mRNA levels of PDE5, a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs, that regulates arterious vascular tone by lowering cGMP levels. Cyclic GMP 147-151 phosphodiesterase 5A Homo sapiens 31-35 31248114-10 2019 However, further increases in cGMP from higher sildenafil concentrations activate PDE2 and consequently decrease cAMP, which demonstrates crosstalk between cAMP and cGMP via PDE2, PDE3, and PDE5. Cyclic GMP 30-34 phosphodiesterase 5A Homo sapiens 190-194 31248114-10 2019 However, further increases in cGMP from higher sildenafil concentrations activate PDE2 and consequently decrease cAMP, which demonstrates crosstalk between cAMP and cGMP via PDE2, PDE3, and PDE5. Cyclic GMP 165-169 phosphodiesterase 5A Homo sapiens 190-194 30388886-0 2019 Hydroalcoholic Extract of Levisticum officinale Increases cGMP Signaling Pathway by Down-Regulating PDE5 Expression and Induction of Apoptosis in MCF-7 and MDA-MB-468 Breast Cancer Cell Lines Background: This study aimed to investigate Levisticum officinale hydroalcoholic extract (LOHE) effect on both cGMP signaling pathway and phosphodiesterase 5 (PDE5) gene expression pattern and to examine the role of LOHE in apoptosis induction of MCF-7 and MDA-MB-468 cell lines. Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 351-355 30292404-1 2018 BACKGROUND: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, is known to increase the intracellular level of cyclic guanosine monophosphate (cGMP), which causes vasodilation. Cyclic GMP 112-142 phosphodiesterase 5A Homo sapiens 26-45 30958912-0 2019 Activation of cGMP/PKG/p65 signaling associated with PDE5-Is downregulates CCL5 secretion by CD8 + T cells in benign prostatic hyperplasia. Cyclic GMP 14-18 phosphodiesterase 5A Homo sapiens 53-57 30958912-2 2019 Phosphodiesterase type 5 inhibitors (PDE5-Is) used to treat BPH could upregulate the cyclic guanosine monophosphate (cGMP)-dependent protein kinase G (PKG) signaling, which was shown to blunt inflammation in the prostate. Cyclic GMP 85-115 phosphodiesterase 5A Homo sapiens 37-41 30958912-2 2019 Phosphodiesterase type 5 inhibitors (PDE5-Is) used to treat BPH could upregulate the cyclic guanosine monophosphate (cGMP)-dependent protein kinase G (PKG) signaling, which was shown to blunt inflammation in the prostate. Cyclic GMP 117-121 phosphodiesterase 5A Homo sapiens 37-41 30189250-9 2019 PDE5-specific inhibitors, such as sildenafil, show considerable anti-tumorigenic potential against CRC by amplifying the GUCY2C/cGMP signaling pathway, but cannot achieve complete anti-tumorigenic effects. Cyclic GMP 128-132 phosphodiesterase 5A Homo sapiens 0-4 30747070-1 2019 BACKGROUND: PDE5A is a phosphodiesterase which specifically hydrolyzes the cGMP to GMP. Cyclic GMP 75-79 phosphodiesterase 5A Homo sapiens 12-17 30958912-13 2019 CONCLUSIONS: Our results indicate that the upregulation of the cGMP/PKG/p65 signaling reduces CCL5 secretion in CD8 + T cells, which in turn decreases the proliferation of BECs in low androgen conditions, suggesting that the combination of 5alpha reductase inhibitors lowering androgen levels and PDE5-Is may be a novel, more effective treatment for BPH patients. Cyclic GMP 63-67 phosphodiesterase 5A Homo sapiens 297-301 30761523-2 2019 In preclinical models, the combination of a PDE5 inhibitor (PDE5i) with a neprilysin inhibitor augments natriuretic peptide bioactivity, promotes cGMP signalling, and reverses the structural and haemodynamic deficits that characterize PAH. Cyclic GMP 146-150 phosphodiesterase 5A Homo sapiens 44-48 30381900-1 2019 Phosphodiesterase type 5 (PDE-5) is an important enzyme involved in the hydrolysis of cyclic guanosine monophosphate (cGMP) to guanosine monophosphate (GMP). Cyclic GMP 86-116 phosphodiesterase 5A Homo sapiens 0-24 30381900-1 2019 Phosphodiesterase type 5 (PDE-5) is an important enzyme involved in the hydrolysis of cyclic guanosine monophosphate (cGMP) to guanosine monophosphate (GMP). Cyclic GMP 86-116 phosphodiesterase 5A Homo sapiens 26-31 30381900-1 2019 Phosphodiesterase type 5 (PDE-5) is an important enzyme involved in the hydrolysis of cyclic guanosine monophosphate (cGMP) to guanosine monophosphate (GMP). Cyclic GMP 118-122 phosphodiesterase 5A Homo sapiens 0-24 30381900-1 2019 Phosphodiesterase type 5 (PDE-5) is an important enzyme involved in the hydrolysis of cyclic guanosine monophosphate (cGMP) to guanosine monophosphate (GMP). Cyclic GMP 118-122 phosphodiesterase 5A Homo sapiens 26-31 30258189-4 2019 Further on, new translational laboratory and animal research from our group initiated a second phase when we proposed an alternative therapeutic schedule and mechanism of action for PDE5 inhibitors (PDE5i) in both corporal veno-occlusive dysfunction (CVOD) and Peyronie"s disease (PD), specifically, continuous long-term administration (CLTA) to achieve sustained levels of cGMP within the penis. Cyclic GMP 374-378 phosphodiesterase 5A Homo sapiens 182-186 30590671-0 2019 The cGMP-Degrading Enzyme Phosphodiesterase-5 (PDE5) in Cerebral Small Arteries of Older People. Cyclic GMP 4-8 phosphodiesterase 5A Homo sapiens 47-51 30590671-3 2019 Here, we investigated whether the cGMP-degrading enzyme phosphodiesterase-5 (PDE5) is present in small penetrating arteries in the deep subcortical white matter of older people. Cyclic GMP 34-38 phosphodiesterase 5A Homo sapiens 77-81 30705876-4 2018 Phosphodiesterase type 5 (PDE5) inhibitors are used to treat erectile dysfunction through the selective inhibition of PDE5 that is responsible for cGMP degradation in the corpus cavernosum. Cyclic GMP 147-151 phosphodiesterase 5A Homo sapiens 0-24 30705876-4 2018 Phosphodiesterase type 5 (PDE5) inhibitors are used to treat erectile dysfunction through the selective inhibition of PDE5 that is responsible for cGMP degradation in the corpus cavernosum. Cyclic GMP 147-151 phosphodiesterase 5A Homo sapiens 26-30 30705876-4 2018 Phosphodiesterase type 5 (PDE5) inhibitors are used to treat erectile dysfunction through the selective inhibition of PDE5 that is responsible for cGMP degradation in the corpus cavernosum. Cyclic GMP 147-151 phosphodiesterase 5A Homo sapiens 118-122 30292404-1 2018 BACKGROUND: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, is known to increase the intracellular level of cyclic guanosine monophosphate (cGMP), which causes vasodilation. Cyclic GMP 112-142 phosphodiesterase 5A Homo sapiens 47-51 30292404-1 2018 BACKGROUND: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, is known to increase the intracellular level of cyclic guanosine monophosphate (cGMP), which causes vasodilation. Cyclic GMP 144-148 phosphodiesterase 5A Homo sapiens 26-45 30292404-1 2018 BACKGROUND: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, is known to increase the intracellular level of cyclic guanosine monophosphate (cGMP), which causes vasodilation. Cyclic GMP 144-148 phosphodiesterase 5A Homo sapiens 47-51 30245400-4 2018 Further vasorelaxant activity assessments revealed that these PDE5 inhibitors also exhibited significant angiectasis on the norepinephrine-precontracted 3rd-order mesenteric arteries (110-150 mum) via NO-sGC-cGMP pathway, implying their further application for the treatment of vascular diseases. Cyclic GMP 208-212 phosphodiesterase 5A Homo sapiens 62-66 30352768-5 2018 Effects of NO is augmented by inhibiting degradation of the second messenger cyclic guanosine monophosphate (cGMP) using sildenafil and tadalafil, both of which inhibit the enzyme phosphodiesterase 5 (PDE5). Cyclic GMP 77-107 phosphodiesterase 5A Homo sapiens 180-199 30352768-5 2018 Effects of NO is augmented by inhibiting degradation of the second messenger cyclic guanosine monophosphate (cGMP) using sildenafil and tadalafil, both of which inhibit the enzyme phosphodiesterase 5 (PDE5). Cyclic GMP 77-107 phosphodiesterase 5A Homo sapiens 201-205 30352768-5 2018 Effects of NO is augmented by inhibiting degradation of the second messenger cyclic guanosine monophosphate (cGMP) using sildenafil and tadalafil, both of which inhibit the enzyme phosphodiesterase 5 (PDE5). Cyclic GMP 109-113 phosphodiesterase 5A Homo sapiens 180-199 30352768-5 2018 Effects of NO is augmented by inhibiting degradation of the second messenger cyclic guanosine monophosphate (cGMP) using sildenafil and tadalafil, both of which inhibit the enzyme phosphodiesterase 5 (PDE5). Cyclic GMP 109-113 phosphodiesterase 5A Homo sapiens 201-205 30701875-2 2018 Until recently, the only therapeutic strategy to influence the molecular pathway of nitric oxide (NO) - soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) was the use of phosphodiesterase type 5 inhibitors (PDE-5 inhibitors), such as sildenafil. Cyclic GMP 138-168 phosphodiesterase 5A Homo sapiens 228-233 29920215-2 2018 Tadalafil, an inhibitor of the phosphodiesterase (PDE) type 5 (PDE5) that specifically hydrolyzes cGMP, is increasingly used to treat children with pulmonary arterial hypertension (PAH), but the effect of tadalafil on bone growth and strength has not been previously investigated. Cyclic GMP 98-102 phosphodiesterase 5A Homo sapiens 63-67 29920215-4 2018 We detected robust expression of PDE5 as the major phosphodiesterase hydrolyzing cGMP. Cyclic GMP 81-85 phosphodiesterase 5A Homo sapiens 33-37 29668326-4 2018 To enhance cGMP signaling, pharmacological inhibition of phosphodiesterase 5 (PDE5) was performed. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 57-76 29668326-4 2018 To enhance cGMP signaling, pharmacological inhibition of phosphodiesterase 5 (PDE5) was performed. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 78-82 29667180-5 2018 In the present review, the pharmacological basis of the NO/cGMP pathway and the rationale and clinical use of PDE5 inhibitors in different diseases are discussed. Cyclic GMP 59-63 phosphodiesterase 5A Homo sapiens 110-114 29738821-3 2018 Nitrates, supplementing NO and, PDE5 inhibitors preventing cGMP degradation, are used for angina pectoris treatment and the treatment of pulmonary arterial hypertension (PAH), respectively. Cyclic GMP 59-63 phosphodiesterase 5A Homo sapiens 32-36 30701875-2 2018 Until recently, the only therapeutic strategy to influence the molecular pathway of nitric oxide (NO) - soluble guanylate cyclase (sGC) - cyclic guanosine monophosphate (cGMP) was the use of phosphodiesterase type 5 inhibitors (PDE-5 inhibitors), such as sildenafil. Cyclic GMP 170-174 phosphodiesterase 5A Homo sapiens 228-233 29462984-10 2018 Specifically, the models predict, unexpectedly, a strong effect of pharmacological inhibitors of cGMP-specific PDE5 on the cGMP/cAMP cross-talk. Cyclic GMP 97-101 phosphodiesterase 5A Homo sapiens 111-115 29462984-10 2018 Specifically, the models predict, unexpectedly, a strong effect of pharmacological inhibitors of cGMP-specific PDE5 on the cGMP/cAMP cross-talk. Cyclic GMP 123-127 phosphodiesterase 5A Homo sapiens 111-115 29462984-12 2018 In conclusion, increased NO signalling or PDE5 inhibition are attractive ways of increasing cGMP-cAMP cross-talk selectively in platelets. Cyclic GMP 92-96 phosphodiesterase 5A Homo sapiens 42-46 29416006-7 2018 CSC elimination by PDE5 inhibition was not dependent on PKG signaling, and we suggest a novel mechanism in which PDE5 inhibition leads to elevated cGMP levels that stimulate cAMP/PKA signaling to eliminate CSCs. Cyclic GMP 147-151 phosphodiesterase 5A Homo sapiens 19-23 29416006-7 2018 CSC elimination by PDE5 inhibition was not dependent on PKG signaling, and we suggest a novel mechanism in which PDE5 inhibition leads to elevated cGMP levels that stimulate cAMP/PKA signaling to eliminate CSCs. Cyclic GMP 147-151 phosphodiesterase 5A Homo sapiens 113-117 28964803-2 2017 Using isolated and/or recombinant PDE5, it has been demonstrated that cGMP can increase the affinity of this enzyme for sildenafil and tadalafil. Cyclic GMP 70-74 phosphodiesterase 5A Homo sapiens 34-38 29132113-6 2018 The new approach takes advantage of Forster Resonance Energy Transfer (FRET) between, as the donor, a fluorescein-like diarsenical probe able to covalently bind a tetracysteine motif fused to the recombinant PDE5 catalytic domain and, as the acceptor, a rhodamine probe covalently bound to the pseudosubstrate cGMPS. Cyclic GMP 310-315 phosphodiesterase 5A Homo sapiens 208-212 29132113-7 2018 The FRET efficiency decreases when a competitive ligand binds the PDE5 catalytic site and displaces the cGMPS-rhodamine conjugate. Cyclic GMP 104-109 phosphodiesterase 5A Homo sapiens 66-70 29132113-8 2018 We have structurally investigated the PDE5/cGMPS-rhodamine complex by molecular modelling and have used the FRET signal to quantitatively characterize its binding equilibrium. Cyclic GMP 43-48 phosphodiesterase 5A Homo sapiens 38-42 28982942-2 2018 This occurs via increased cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase-5 (PDE-5). Cyclic GMP 26-56 phosphodiesterase 5A Homo sapiens 89-108 28982942-2 2018 This occurs via increased cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase-5 (PDE-5). Cyclic GMP 26-56 phosphodiesterase 5A Homo sapiens 110-115 28982942-2 2018 This occurs via increased cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase-5 (PDE-5). Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 89-108 28982942-2 2018 This occurs via increased cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase-5 (PDE-5). Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 110-115 28982942-14 2018 These data suggest NO-independent activation of cGMP occurs at exercise onset; thus PDE-5 inhibition may improve vasodilation in pathologies where NO bioavailability is impaired. Cyclic GMP 48-52 phosphodiesterase 5A Homo sapiens 84-89 28982942-15 2018 NEW & NOTEWORTHY We show that when NO bioavailability is reduced, PDE-5 inhibition can restore vasodilation onset kinetics of exercise-mediated vasodilation via NO-independent cGMP pathways. Cyclic GMP 180-184 phosphodiesterase 5A Homo sapiens 70-75 29301746-9 2018 Taken together, the results demonstrate that targeting cGMP with either PDE5 inhibitors or GCC agonists alters epithelial homeostasis in a manner that reduces neoplasia, and suggests that this could be a viable chemoprevention strategy for patients at high risk of developing colorectal cancer. Cyclic GMP 55-59 phosphodiesterase 5A Homo sapiens 72-76 28213937-1 2018 Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cGMP into 5"-GMP, thereby regulating its intracellular concentrations. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 0-24 28213937-1 2018 Phosphodiesterase type 5 (PDE5) selectively hydrolyses the second messenger cGMP into 5"-GMP, thereby regulating its intracellular concentrations. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 26-30 28964803-3 2017 We thus hypothesized that in cells expressing the nitric oxide - soluble guanylyl cyclase - cyclic guanosine monophosphate - PDE5 (NO-sGC-cGMP-PDE5) pathway such as platelets, the presence of NO increases the intracellular cGMP content and thus promotes the intracellular accumulation of sildenafil or tadalafil. Cyclic GMP 92-122 phosphodiesterase 5A Homo sapiens 125-129 28964803-3 2017 We thus hypothesized that in cells expressing the nitric oxide - soluble guanylyl cyclase - cyclic guanosine monophosphate - PDE5 (NO-sGC-cGMP-PDE5) pathway such as platelets, the presence of NO increases the intracellular cGMP content and thus promotes the intracellular accumulation of sildenafil or tadalafil. Cyclic GMP 92-122 phosphodiesterase 5A Homo sapiens 131-147 28964803-3 2017 We thus hypothesized that in cells expressing the nitric oxide - soluble guanylyl cyclase - cyclic guanosine monophosphate - PDE5 (NO-sGC-cGMP-PDE5) pathway such as platelets, the presence of NO increases the intracellular cGMP content and thus promotes the intracellular accumulation of sildenafil or tadalafil. Cyclic GMP 138-142 phosphodiesterase 5A Homo sapiens 125-129 28964803-10 2017 Our data demonstrate that intracellular cGMP increases intracellular PDE5 inhibitor concentrations most likely by raising the affinity of these compounds for PDE5. Cyclic GMP 40-44 phosphodiesterase 5A Homo sapiens 69-73 28964803-10 2017 Our data demonstrate that intracellular cGMP increases intracellular PDE5 inhibitor concentrations most likely by raising the affinity of these compounds for PDE5. Cyclic GMP 40-44 phosphodiesterase 5A Homo sapiens 158-162 29228762-3 2017 Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a promising approach to restore normal intracellular cyclic guanosine monophosphate (cGMP) signalling, and thereby resulting into the activation of various downstream molecules to inhibit proliferation, motility and invasion of certain cancer cells. Cyclic GMP 140-170 phosphodiesterase 5A Homo sapiens 40-64 29228762-3 2017 Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a promising approach to restore normal intracellular cyclic guanosine monophosphate (cGMP) signalling, and thereby resulting into the activation of various downstream molecules to inhibit proliferation, motility and invasion of certain cancer cells. Cyclic GMP 140-170 phosphodiesterase 5A Homo sapiens 66-70 29228762-3 2017 Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a promising approach to restore normal intracellular cyclic guanosine monophosphate (cGMP) signalling, and thereby resulting into the activation of various downstream molecules to inhibit proliferation, motility and invasion of certain cancer cells. Cyclic GMP 172-176 phosphodiesterase 5A Homo sapiens 40-64 29228762-3 2017 Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a promising approach to restore normal intracellular cyclic guanosine monophosphate (cGMP) signalling, and thereby resulting into the activation of various downstream molecules to inhibit proliferation, motility and invasion of certain cancer cells. Cyclic GMP 172-176 phosphodiesterase 5A Homo sapiens 66-70 28506928-0 2017 Distinct phosphodiesterase 5A-containing compartments allow selective regulation of cGMP-dependent signalling in human arterial smooth muscle cells. Cyclic GMP 84-88 phosphodiesterase 5A Homo sapiens 9-29 28705807-9 2017 NO generates H2S via cGMP/PKG pathway, and H2S, in turn, inhibits PDE5 activity and augments NO-induced cGMP levels. Cyclic GMP 21-25 phosphodiesterase 5A Homo sapiens 66-70 28705807-12 2017 H2S inhibits phosphodiesterase 5 activity to augment cGMP levels in response to NO, which, in turn, via cGMP/PKG pathway, generates H2S. Cyclic GMP 53-57 phosphodiesterase 5A Homo sapiens 13-32 28648945-11 2017 This review demonstrates both neuroprotective and neurorestorative effects of PDE5i in animal models of stroke, though the specific underlying signaling pathways relating to PDE5 inhibition and cGMP may remain serendipitous in some studies. Cyclic GMP 194-198 phosphodiesterase 5A Homo sapiens 78-82 27581752-3 2017 PDE type 5 (PDE5) inhibitors enhance the vasodilatory effects of cGMP in the corpus cavernosum and they are used to treat erectile dysfunction. Cyclic GMP 65-69 phosphodiesterase 5A Homo sapiens 0-10 27581752-3 2017 PDE type 5 (PDE5) inhibitors enhance the vasodilatory effects of cGMP in the corpus cavernosum and they are used to treat erectile dysfunction. Cyclic GMP 65-69 phosphodiesterase 5A Homo sapiens 12-16 28506928-2 2017 Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca2+ in human platelets. Cyclic GMP 46-50 phosphodiesterase 5A Homo sapiens 104-124 28506928-2 2017 Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca2+ in human platelets. Cyclic GMP 46-50 phosphodiesterase 5A Homo sapiens 126-131 28506928-2 2017 Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca2+ in human platelets. Cyclic GMP 46-50 phosphodiesterase 5A Homo sapiens 292-297 28506928-4 2017 In addition, we report that PDE5A also regulates HASMC functions via events independent of PKG, but rather through actions coordinated by competitive cGMP-mediated inhibition of cAMP hydrolysis by the so-called cGMP-inhibited cAMP PDE, namely phosphodiesterase 3A (PDE3A). Cyclic GMP 150-154 phosphodiesterase 5A Homo sapiens 28-33 28506928-4 2017 In addition, we report that PDE5A also regulates HASMC functions via events independent of PKG, but rather through actions coordinated by competitive cGMP-mediated inhibition of cAMP hydrolysis by the so-called cGMP-inhibited cAMP PDE, namely phosphodiesterase 3A (PDE3A). Cyclic GMP 211-215 phosphodiesterase 5A Homo sapiens 28-33 28506928-7 2017 Our findings provide insight into the existence of distinct "pools" of PDE5A in HASMC and support the idea that these discrete compartments regulate distinct cGMP-dependent events. Cyclic GMP 158-162 phosphodiesterase 5A Homo sapiens 71-76 28506928-8 2017 As a corollary, we suggest that it may be possible to target these distinct PDE5A-regulated pools and in so-doing differentially impact selected cGMP-regulated functions in these cells. Cyclic GMP 145-149 phosphodiesterase 5A Homo sapiens 76-81 28211580-3 2017 Complete IC50 plots for all analogues were performed for PDE5A-dependent cGMP hydrolysis. Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 57-62 28719717-8 2017 We speculate that the possible mechanism for these findings is that PDE5 inhibitors block degradation of cyclic guanosine monophosphate (cGMP) and induce dilation of the cochlear microcirculation, resulting in an increase in cochlear blood flow. Cyclic GMP 105-135 phosphodiesterase 5A Homo sapiens 68-72 28719717-8 2017 We speculate that the possible mechanism for these findings is that PDE5 inhibitors block degradation of cyclic guanosine monophosphate (cGMP) and induce dilation of the cochlear microcirculation, resulting in an increase in cochlear blood flow. Cyclic GMP 137-141 phosphodiesterase 5A Homo sapiens 68-72 28211580-10 2017 CONCLUSIONS: Sildenafil analogues that inhibit cellular cGMP efflux are potent inhibitors of PDE5A and PDE6C. Cyclic GMP 56-60 phosphodiesterase 5A Homo sapiens 93-98 28099939-1 2017 Expression of type 5 phosphodiesterase (PDE5), a cGMP-specific hydrolytic enzyme, is frequently altered in human cancer, but its specific role in tumorigenesis remains controversial. Cyclic GMP 49-53 phosphodiesterase 5A Homo sapiens 40-44 27662514-3 2017 The PDE1A, PDE4D, PDE5A, PDE8A, and PDE8B are granulosa cell specific PDEs that hydrolyze adenosine 3",5"-cyclic monophosphate (cAMP) as well as guanosine 3",5"-cyclic monophosphate (cGMP) with different affinities. Cyclic GMP 145-181 phosphodiesterase 5A Homo sapiens 18-23 27662514-3 2017 The PDE1A, PDE4D, PDE5A, PDE8A, and PDE8B are granulosa cell specific PDEs that hydrolyze adenosine 3",5"-cyclic monophosphate (cAMP) as well as guanosine 3",5"-cyclic monophosphate (cGMP) with different affinities. Cyclic GMP 183-187 phosphodiesterase 5A Homo sapiens 18-23 28379598-2 2017 It is a selective phosphodiesterase type 5-enzyme inhibitor able to potentiate the downstream effects of nitric oxide on smooth muscle relaxation and vasodilation through its effects on the cyclic guanosine monophosphate (c-GMP) pathway in the erectile tissue of the penis. Cyclic GMP 190-220 phosphodiesterase 5A Homo sapiens 18-42 28379598-2 2017 It is a selective phosphodiesterase type 5-enzyme inhibitor able to potentiate the downstream effects of nitric oxide on smooth muscle relaxation and vasodilation through its effects on the cyclic guanosine monophosphate (c-GMP) pathway in the erectile tissue of the penis. Cyclic GMP 222-227 phosphodiesterase 5A Homo sapiens 18-42 28722423-0 2017 Generation of a cGMP Indicator with an Expanded Dynamic Range by Optimization of Amino Acid Linkers between a Fluorescent Protein and PDE5alpha. Cyclic GMP 16-20 phosphodiesterase 5A Homo sapiens 134-143 28123846-1 2017 Phosphodiesterase 5 (PDE-5) is a major isoform of cGMP phosphodiesterase in diverse tissues and plays a critical role in regulating intracellular cGMP concentrations. Cyclic GMP 50-54 phosphodiesterase 5A Homo sapiens 0-19 27732797-3 2017 Seven PDE family members are physiologically relevant to regulating cardiac function, disease remodeling of the heart, or both: PDE1 and PDE2, both dual-substrate (cAMP and cGMP) esterases; PDE3, PDE4, and PDE8, which principally hydrolyze cAMP; and PDE5A and PDE9A, which target cGMP. Cyclic GMP 280-284 phosphodiesterase 5A Homo sapiens 250-255 27903966-1 2017 Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. Cyclic GMP 63-67 phosphodiesterase 5A Homo sapiens 0-19 27903966-1 2017 Phosphodiesterase 5 (PDE5) inhibitors prevent the breakdown of cGMP that results in prolonged protein kinase G activation and the generation of nitric oxide. Cyclic GMP 63-67 phosphodiesterase 5A Homo sapiens 21-25 29202488-4 2017 Moreover, we determined whether the effects of tadalafil would be reflected in variation of plasma levels of cGMP and NO, two important molecules involved in PDE5Is signaling. Cyclic GMP 109-113 phosphodiesterase 5A Homo sapiens 158-162 27784679-8 2017 Further downstream, H2S inhibits the vascular cGMP phosphodiesterase (PDE5), thereby prolonging the biological half-life of cGMP. Cyclic GMP 46-50 phosphodiesterase 5A Homo sapiens 70-74 28123846-1 2017 Phosphodiesterase 5 (PDE-5) is a major isoform of cGMP phosphodiesterase in diverse tissues and plays a critical role in regulating intracellular cGMP concentrations. Cyclic GMP 50-54 phosphodiesterase 5A Homo sapiens 21-26 28316997-2 2017 Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. Cyclic GMP 39-69 phosphodiesterase 5A Homo sapiens 120-124 28316997-2 2017 Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. Cyclic GMP 71-75 phosphodiesterase 5A Homo sapiens 120-124 28316997-2 2017 Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. Cyclic GMP 95-99 phosphodiesterase 5A Homo sapiens 120-124 27624510-3 2016 PDE-5 inhibitor action is materialized through the inhibition of the cyclic guanosine monophosphate (cGMP) enzyme. Cyclic GMP 69-99 phosphodiesterase 5A Homo sapiens 0-5 27113485-3 2016 Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 147-151 27113485-3 2016 Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. Cyclic GMP 97-101 phosphodiesterase 5A Homo sapiens 147-151 27624510-3 2016 PDE-5 inhibitor action is materialized through the inhibition of the cyclic guanosine monophosphate (cGMP) enzyme. Cyclic GMP 101-105 phosphodiesterase 5A Homo sapiens 0-5 27184830-5 2016 PDE5 is particularly important for the degradation of cGMP in vascular smooth muscle, and PDE5 inhibitors are used to treat erectile dysfunction and pulmonary hypertension. Cyclic GMP 54-58 phosphodiesterase 5A Homo sapiens 0-4 27179930-7 2016 Together, the present study has uncovered that PDE/cGMP/PKG signal targets to Hippo/TAZ pathway in maintaining stemness of PCSC, and suggested that PDE5 inhibitors in combination with chemotherapeutic agents could effectively prevent initiation, metastasis, and relapse of prostate cancer. Cyclic GMP 51-55 phosphodiesterase 5A Homo sapiens 148-152 27419107-6 2016 Moreover, the studies to evaluate the influence of nitric oxide (NO) and guanosine monophosphate (cGMP) signaling pathway associated with PDE5 showed both cancer reduction and cancer development. Cyclic GMP 98-102 phosphodiesterase 5A Homo sapiens 138-142 28163539-7 2016 The opening of these channels could have been due to the action of raised intracellular levels of cGMP due to inhibition of PDE-5 by tadalafil. Cyclic GMP 98-102 phosphodiesterase 5A Homo sapiens 124-129 26620458-2 2016 The constant discoveries of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) cell-signaling pathway for smooth muscle (SM) control in other urogenital tracts (UGTs) make PDE5-Is promising pharmacologic agents against other benign urological diseases. Cyclic GMP 46-76 phosphodiesterase 5A Homo sapiens 177-181 26620458-2 2016 The constant discoveries of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) cell-signaling pathway for smooth muscle (SM) control in other urogenital tracts (UGTs) make PDE5-Is promising pharmacologic agents against other benign urological diseases. Cyclic GMP 78-82 phosphodiesterase 5A Homo sapiens 177-181 29057299-3 2017 cGMP degradation via PDE5 acts as a brake on this pathway. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 21-25 26108184-7 2016 Furthermore, sildenafil and yonkenafil increased the cyclic guanosine monophosphate (cGMP) level in N9 microglia, and 8-Br-cGMP, an analogue of cGMP, downregulates extracellular signal-regulated kinases 1 and 2 (ERK1/2)/the NF-kappaB pathway, suggesting that sildenafil and yonkenafil inhibit microglial activation by decreasing PDE5 expression and increasing the cGMP level. Cyclic GMP 123-127 phosphodiesterase 5A Homo sapiens 329-333 27398244-4 2016 The main enzyme involved in the termination of cGMP effects is phosphodiesterase enzyme 5 (PDE-5), which is overexpressed in ventricular hypertrophy and heart failure. Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 63-89 27398244-4 2016 The main enzyme involved in the termination of cGMP effects is phosphodiesterase enzyme 5 (PDE-5), which is overexpressed in ventricular hypertrophy and heart failure. Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 91-96 26108184-7 2016 Furthermore, sildenafil and yonkenafil increased the cyclic guanosine monophosphate (cGMP) level in N9 microglia, and 8-Br-cGMP, an analogue of cGMP, downregulates extracellular signal-regulated kinases 1 and 2 (ERK1/2)/the NF-kappaB pathway, suggesting that sildenafil and yonkenafil inhibit microglial activation by decreasing PDE5 expression and increasing the cGMP level. Cyclic GMP 123-127 phosphodiesterase 5A Homo sapiens 329-333 27872007-1 2016 INTRODUCTION: Phosphodiesterase 5 (PDE5) inhibitors (PDE5i) have been used clinically for the treatment of erectile dysfunction, acting on the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway. Cyclic GMP 156-186 phosphodiesterase 5A Homo sapiens 14-33 27079836-3 2016 Several cGMPs degrading phosphodiesterases (PDEs), including PDE1 and PDE5, play an important role in the regulation of cGMP signaling. Cyclic GMP 8-13 phosphodiesterase 5A Homo sapiens 70-74 27079836-3 2016 Several cGMPs degrading phosphodiesterases (PDEs), including PDE1 and PDE5, play an important role in the regulation of cGMP signaling. Cyclic GMP 8-12 phosphodiesterase 5A Homo sapiens 70-74 26551887-6 2016 Several activators of soluble GC (sGC), as well as inhibitors of PDE5, increased intracellular cGMP, reduced cell viability, and induced apoptosis in HNSCC cells. Cyclic GMP 95-99 phosphodiesterase 5A Homo sapiens 65-69 26967220-1 2016 Phosphodiesterase 5 (PDE5) is a critical component of the cGMP-PKG axis of cellular signaling in neurons, and inhibition of PDE5 has been shown to be therapeutic in a wide range of neurologic conditions in animal models. Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 0-19 26967220-1 2016 Phosphodiesterase 5 (PDE5) is a critical component of the cGMP-PKG axis of cellular signaling in neurons, and inhibition of PDE5 has been shown to be therapeutic in a wide range of neurologic conditions in animal models. Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 21-25 26967220-1 2016 Phosphodiesterase 5 (PDE5) is a critical component of the cGMP-PKG axis of cellular signaling in neurons, and inhibition of PDE5 has been shown to be therapeutic in a wide range of neurologic conditions in animal models. Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 124-128 26773602-11 2016 Finally, we show that PDE2 compensates for inhibition of PDE5 both in terms of cGMP and cAMP dynamics, leading to cGMP elevation and increased PKG activation, while maintaining whole-cell beta-adrenergic responses similar to that prior to PDE5 inhibition. Cyclic GMP 79-83 phosphodiesterase 5A Homo sapiens 57-61 26773602-11 2016 Finally, we show that PDE2 compensates for inhibition of PDE5 both in terms of cGMP and cAMP dynamics, leading to cGMP elevation and increased PKG activation, while maintaining whole-cell beta-adrenergic responses similar to that prior to PDE5 inhibition. Cyclic GMP 114-118 phosphodiesterase 5A Homo sapiens 57-61 27451093-4 2016 Basic and clinical studies of cGMP regulation through activation of soluble guanylyl cyclase (sGC) or inhibition of cyclic nucleotide phosphodiesterase type 5 (PDE5) have resulted in effective therapies for pulmonary hypertension, erectile dysfunction, and more recently benign prostatic hyperplasia. Cyclic GMP 30-34 phosphodiesterase 5A Homo sapiens 160-164 27872007-1 2016 INTRODUCTION: Phosphodiesterase 5 (PDE5) inhibitors (PDE5i) have been used clinically for the treatment of erectile dysfunction, acting on the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway. Cyclic GMP 156-186 phosphodiesterase 5A Homo sapiens 35-39 27872007-1 2016 INTRODUCTION: Phosphodiesterase 5 (PDE5) inhibitors (PDE5i) have been used clinically for the treatment of erectile dysfunction, acting on the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway. Cyclic GMP 191-195 phosphodiesterase 5A Homo sapiens 14-33 27872007-1 2016 INTRODUCTION: Phosphodiesterase 5 (PDE5) inhibitors (PDE5i) have been used clinically for the treatment of erectile dysfunction, acting on the nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway. Cyclic GMP 191-195 phosphodiesterase 5A Homo sapiens 35-39 26272735-5 2015 The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 107-126 26432842-2 2015 We recently demonstrated that inhibition of cGMP-binding phosphodiesterase 5 (PDE5) increased blood flow to contracting skeletal muscle of older but not young human subjects. Cyclic GMP 44-48 phosphodiesterase 5A Homo sapiens 78-82 26387628-5 2015 The phosphodiesterase (PDE) 5 inhibitor sildenafil increased the intracellular cGMP levels in skin fibroblasts in a dose-dependent manner. Cyclic GMP 79-83 phosphodiesterase 5A Homo sapiens 23-29 26553865-1 2015 INTRODUCTION: Sildenafil (Viagra ) is a selective phosphodiesterase type 5 (PDE5) inhibitor that block the breakdown of cyclic guanyl monophosphate (cGMP) leading to relaxation of the smooth muscles of the corpus cavernous and an increase in blood flow resulting in penile erection. Cyclic GMP 149-153 phosphodiesterase 5A Homo sapiens 50-74 26553865-1 2015 INTRODUCTION: Sildenafil (Viagra ) is a selective phosphodiesterase type 5 (PDE5) inhibitor that block the breakdown of cyclic guanyl monophosphate (cGMP) leading to relaxation of the smooth muscles of the corpus cavernous and an increase in blood flow resulting in penile erection. Cyclic GMP 149-153 phosphodiesterase 5A Homo sapiens 76-80 26299804-2 2015 Here we report that the cGMP PDE isozymes, PDE5 and 10, are elevated in colon tumor cells compared with normal colonocytes, and that inhibitors and siRNAs can selectively suppress colon tumor cell growth. Cyclic GMP 24-28 phosphodiesterase 5A Homo sapiens 43-47 26205960-2 2015 Intracellular concentrations of cGMP are thought to be determined by the action of cGMP-generating guanylyl cyclases (sensitive to nitric oxide or natriuretic peptides) and cGMP-degrading phosphodiesterases (PDE1, PDE3, and PDE5). Cyclic GMP 32-36 phosphodiesterase 5A Homo sapiens 224-228 26205960-5 2015 PDE5 was the major cGMP phosphodiesterase responsible for reducing nitric oxide- and natriuretic peptide-induced cGMP signals. Cyclic GMP 19-23 phosphodiesterase 5A Homo sapiens 0-4 26205960-7 2015 Unexpectedly, we found that cGMP is transported out of the cells by the ABC transporter multidrug resistance-associated protein 4 and this export turned out to be of similar importance for intracellular cGMP signals as degradation by PDE5. Cyclic GMP 28-32 phosphodiesterase 5A Homo sapiens 234-238 28162283-10 2015 The iNOS/NO/cGMP/TACE pathway can be augmented by PDE5 inhibitors and reduce organ injury in the setting of sepsis. Cyclic GMP 12-16 phosphodiesterase 5A Homo sapiens 50-54 26272735-5 2015 The current study aimed to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 128-132 25747598-3 2015 Although PDE5 has been suggested to play a significant role in the breakdown of cGMP in cardiomyocytes and hence PKG regulation in the myocardium, the RELAX trial, which tested effect of PDE5 inhibition on exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) failed to show a beneficial effect. Cyclic GMP 80-84 phosphodiesterase 5A Homo sapiens 9-13 26047999-3 2015 The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. Cyclic GMP 143-173 phosphodiesterase 5A Homo sapiens 29-34 26328208-6 2015 By increasing intracellular cGMP levels, PDE5 inhibitors have been shown to be effective in the treatment of ED. Cyclic GMP 28-32 phosphodiesterase 5A Homo sapiens 41-45 25801159-1 2015 Cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type-5 (PDE5), a clinically proven target to treat erectile dysfunction and diseases associated with lower cGMP levels in humans, is present in corpus cavernosum, heart, lung, platelets, prostate, urethra, bladder, liver, brain, and stomach. Cyclic GMP 0-30 phosphodiesterase 5A Homo sapiens 47-71 25801159-1 2015 Cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type-5 (PDE5), a clinically proven target to treat erectile dysfunction and diseases associated with lower cGMP levels in humans, is present in corpus cavernosum, heart, lung, platelets, prostate, urethra, bladder, liver, brain, and stomach. Cyclic GMP 0-30 phosphodiesterase 5A Homo sapiens 73-77 25801159-1 2015 Cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type-5 (PDE5), a clinically proven target to treat erectile dysfunction and diseases associated with lower cGMP levels in humans, is present in corpus cavernosum, heart, lung, platelets, prostate, urethra, bladder, liver, brain, and stomach. Cyclic GMP 32-36 phosphodiesterase 5A Homo sapiens 47-71 25801159-1 2015 Cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type-5 (PDE5), a clinically proven target to treat erectile dysfunction and diseases associated with lower cGMP levels in humans, is present in corpus cavernosum, heart, lung, platelets, prostate, urethra, bladder, liver, brain, and stomach. Cyclic GMP 32-36 phosphodiesterase 5A Homo sapiens 73-77 25801159-1 2015 Cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type-5 (PDE5), a clinically proven target to treat erectile dysfunction and diseases associated with lower cGMP levels in humans, is present in corpus cavernosum, heart, lung, platelets, prostate, urethra, bladder, liver, brain, and stomach. Cyclic GMP 172-176 phosphodiesterase 5A Homo sapiens 47-71 25801159-1 2015 Cyclic guanosine monophosphate (cGMP) specific phosphodiesterase type-5 (PDE5), a clinically proven target to treat erectile dysfunction and diseases associated with lower cGMP levels in humans, is present in corpus cavernosum, heart, lung, platelets, prostate, urethra, bladder, liver, brain, and stomach. Cyclic GMP 172-176 phosphodiesterase 5A Homo sapiens 73-77 25799991-1 2015 Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. Cyclic GMP 0-30 phosphodiesterase 5A Homo sapiens 256-281 25799991-1 2015 Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. Cyclic GMP 0-30 phosphodiesterase 5A Homo sapiens 283-288 25799991-1 2015 Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. Cyclic GMP 32-36 phosphodiesterase 5A Homo sapiens 256-281 25799991-1 2015 Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. Cyclic GMP 32-36 phosphodiesterase 5A Homo sapiens 283-288 25799991-1 2015 Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. Cyclic GMP 210-214 phosphodiesterase 5A Homo sapiens 256-281 25799991-1 2015 Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. Cyclic GMP 210-214 phosphodiesterase 5A Homo sapiens 283-288 25799991-3 2015 Furthermore, although PDE5A regulates nitric-oxide-generated cGMP, nitric oxide signalling is often depressed by heart disease. Cyclic GMP 61-65 phosphodiesterase 5A Homo sapiens 22-27 25445042-2 2014 PDE5 and ABCC5 have similar affinity for cGMP whereas ABCC5 has much higher affinity for cGMP compared with cAMP. Cyclic GMP 41-45 phosphodiesterase 5A Homo sapiens 0-4 25848165-1 2015 cGMP-binding cGMP-specific PDE, PDE5 plays a key role in the hydrolysis of cyclic guanidine monophosphate. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 32-36 25848165-1 2015 cGMP-binding cGMP-specific PDE, PDE5 plays a key role in the hydrolysis of cyclic guanidine monophosphate. Cyclic GMP 13-17 phosphodiesterase 5A Homo sapiens 32-36 25848165-2 2015 Because cGMP mediates vascular functions, a PDE5 inhibitor that elevates cGMP level is an attractive means for vasodilatation and treatment of erectile dysfunction. Cyclic GMP 8-12 phosphodiesterase 5A Homo sapiens 44-48 25848165-2 2015 Because cGMP mediates vascular functions, a PDE5 inhibitor that elevates cGMP level is an attractive means for vasodilatation and treatment of erectile dysfunction. Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 44-48 29264117-3 2015 PDE5 inhibitors mediate their effects through several pathways including cAMP, NO/cGMP, K-channel modulated pathways, and the l-cysteine/H2S pathway. Cyclic GMP 82-86 phosphodiesterase 5A Homo sapiens 0-4 26162831-5 2015 Convincing evidence suggests that H2S can influence the cGMP pathway by inhibiting the phosphodiesterase 5 (PDE-5) activity. Cyclic GMP 56-60 phosphodiesterase 5A Homo sapiens 87-106 26162831-5 2015 Convincing evidence suggests that H2S can influence the cGMP pathway by inhibiting the phosphodiesterase 5 (PDE-5) activity. Cyclic GMP 56-60 phosphodiesterase 5A Homo sapiens 108-113 25560770-5 2015 An increase in protein carbonylation, overexpression of NADPH oxidase and PDE5, an enzyme that inactivates cGMP, was observed in platelets from MD patients compared to controls. Cyclic GMP 107-111 phosphodiesterase 5A Homo sapiens 74-78 25560770-8 2015 The increased activation of intraplatelet arginase and platelet aggregability, in addition to an overexpression of PDE5 and oxidative stress may contribute to alterations in L-arginine-NO-cGMP pathway and in platelet function, and consequently to the increased thrombotic risk in MD. Cyclic GMP 188-192 phosphodiesterase 5A Homo sapiens 115-119 26138471-4 2015 This brief review will focus on two therapies that are already approved for use in the US for other indications: PDE-5 inhibition to preserve nitric oxide - cGMP signaling to promote vasodilation and inhibition of the endothelin type A receptor to reduce vascular contraction. Cyclic GMP 157-161 phosphodiesterase 5A Homo sapiens 113-118 26770022-2 2015 Mechanistically, PDE5-Is produce an anti-inflammatory and neuroprotection effect by increasing expression of nitric oxide synthases and accumulation of cGMP and activating protein kinase G (PKG), the signaling pathway of which is thought to play an important role in the development of several neurodiseases, such as Alzheimer"s disease (AD), Parkinson"s disease (PD), and multiple sclerosis (MS). Cyclic GMP 152-156 phosphodiesterase 5A Homo sapiens 17-21 26037192-7 2015 With the inhibition of PDE-5, the amount of cyclic-guanosine monophosphate (c-GMP) in the smooth vascular muscle cells in the corpus cavernosum increases, leading to a relaxation of muscles and vasodilatation. Cyclic GMP 44-74 phosphodiesterase 5A Homo sapiens 23-28 26037192-7 2015 With the inhibition of PDE-5, the amount of cyclic-guanosine monophosphate (c-GMP) in the smooth vascular muscle cells in the corpus cavernosum increases, leading to a relaxation of muscles and vasodilatation. Cyclic GMP 76-81 phosphodiesterase 5A Homo sapiens 23-28 26583228-4 2014 Until now, the exact catalytic mechanism of the substrate cGMP by PDE5 is still unclear. Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 66-70 26583228-5 2014 Herein, the first computational study on the catalytic hydrolysis mechanism of cGMP for PDE5 (catalytic domain) is performed by employing the state-of-the-art ab initio quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations. Cyclic GMP 79-83 phosphodiesterase 5A Homo sapiens 88-92 26583228-9 2014 The obtained mechanistic insights should be valuable for not only the rational design of more specific inhibitors toward PDE5 but also understanding the general hydrolysis mechanism of cGMP-specific PDEs. Cyclic GMP 185-189 phosphodiesterase 5A Homo sapiens 121-125 25445042-2 2014 PDE5 and ABCC5 have similar affinity for cGMP whereas ABCC5 has much higher affinity for cGMP compared with cAMP. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 0-4 25086928-8 2014 Two stable clones downregulating PDE5A (phosphodiesterase 5A), an enzyme involved in the regulation of cGMP-specific signaling, exhibited no difference in cell proliferation, but reduced motility by 47 and 66 % compared to the empty vector-expressing cells (p = 0.01 and p = 0.005). Cyclic GMP 103-107 phosphodiesterase 5A Homo sapiens 33-38 25244411-1 2014 Phosphodiesterase type 5 (PDE5) plays a key role in regulating the intracellular cyclic GMP (cGMP) concentration, which influences anti-proliferative and pro-apoptotic mechanisms in multiple carcinomas. Cyclic GMP 93-97 phosphodiesterase 5A Homo sapiens 0-24 25244411-1 2014 Phosphodiesterase type 5 (PDE5) plays a key role in regulating the intracellular cyclic GMP (cGMP) concentration, which influences anti-proliferative and pro-apoptotic mechanisms in multiple carcinomas. Cyclic GMP 93-97 phosphodiesterase 5A Homo sapiens 26-30 24977346-9 2014 The present study indicates that PKG may attenuate Akt phosphorylation through protein phosphatase 1, which leads to an augmented cGMP elevation by inhibition of PDE5. Cyclic GMP 130-134 phosphodiesterase 5A Homo sapiens 162-166 25163536-8 2014 CONCLUSIONS: Platelets generate transient, endogenous cGMP signals downstream of NO that are primarily independent of NOS and may be enhanced by inhibition of PDE5. Cyclic GMP 54-58 phosphodiesterase 5A Homo sapiens 159-163 25086928-8 2014 Two stable clones downregulating PDE5A (phosphodiesterase 5A), an enzyme involved in the regulation of cGMP-specific signaling, exhibited no difference in cell proliferation, but reduced motility by 47 and 66 % compared to the empty vector-expressing cells (p = 0.01 and p = 0.005). Cyclic GMP 103-107 phosphodiesterase 5A Homo sapiens 40-60 25247292-0 2014 Role of Ser102 and Ser104 as regulators of cGMP hydrolysis by PDE5A. Cyclic GMP 43-47 phosphodiesterase 5A Homo sapiens 62-67 25043200-5 2014 Phosphodiesterase 5 (PDE5) degrades cGMP to GMP. Cyclic GMP 36-40 phosphodiesterase 5A Homo sapiens 0-19 25043200-5 2014 Phosphodiesterase 5 (PDE5) degrades cGMP to GMP. Cyclic GMP 36-40 phosphodiesterase 5A Homo sapiens 21-25 25247292-2 2014 PDE5A is a cytoplasmic phosphodiesterase which specifically degrades cyclic guanosine monophosphate (cGMP), a cell signaling molecule that plays important roles in neuronal signaling and vascular smooth muscle contraction. Cyclic GMP 69-99 phosphodiesterase 5A Homo sapiens 0-5 25247292-2 2014 PDE5A is a cytoplasmic phosphodiesterase which specifically degrades cyclic guanosine monophosphate (cGMP), a cell signaling molecule that plays important roles in neuronal signaling and vascular smooth muscle contraction. Cyclic GMP 101-105 phosphodiesterase 5A Homo sapiens 0-5 25247292-7 2014 PDE5A-GFP fusion proteins were localized in fixed cells by immunofluorescence and PDE activity was quantified in cell extracts by standard in vitro assay using [3H] cGMP. Cyclic GMP 165-169 phosphodiesterase 5A Homo sapiens 0-5 25247292-11 2014 INTERPRETATION: Ser102 and Ser104 may influence the conformational flexibility of PDE5A, which may in turn influence phosphorylation status, allosteric regulation by cGMP or other as yet unknown regulatory mechanisms for PDE5A. Cyclic GMP 166-170 phosphodiesterase 5A Homo sapiens 82-87 25247292-11 2014 INTERPRETATION: Ser102 and Ser104 may influence the conformational flexibility of PDE5A, which may in turn influence phosphorylation status, allosteric regulation by cGMP or other as yet unknown regulatory mechanisms for PDE5A. Cyclic GMP 166-170 phosphodiesterase 5A Homo sapiens 221-226 25202655-0 2014 Can selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphadiesterase type 5 (PDE 5) offer protection against contrast induced nephropathy? Cyclic GMP 28-58 phosphodiesterase 5A Homo sapiens 101-106 25202655-0 2014 Can selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphadiesterase type 5 (PDE 5) offer protection against contrast induced nephropathy? Cyclic GMP 60-64 phosphodiesterase 5A Homo sapiens 101-106 25202655-3 2014 Augmenting the effect of NO in the renal medulla by the use of selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphadiesterase type 5 (PDE 5) such as sildenafil (Viagra ), vardenafil (Levitra ) or tadalafil (Cialis ) could reduce the severity of the hypoxic insult induced by the contrast medium and reduce the risk of CIN. Cyclic GMP 87-117 phosphodiesterase 5A Homo sapiens 160-165 25202655-3 2014 Augmenting the effect of NO in the renal medulla by the use of selective inhibitors of cyclic guanosine monophosphate (cGMP)-specific phosphadiesterase type 5 (PDE 5) such as sildenafil (Viagra ), vardenafil (Levitra ) or tadalafil (Cialis ) could reduce the severity of the hypoxic insult induced by the contrast medium and reduce the risk of CIN. Cyclic GMP 119-123 phosphodiesterase 5A Homo sapiens 160-165 23925396-4 2013 Sildenafil citrate inhibits type 5-specific phosphodiesterase (PDE5), thus preventing the degradation of cyclic guanosine monophosphate (cGMP) in the muscle and augmenting the vasodilatory effects of NO. Cyclic GMP 105-135 phosphodiesterase 5A Homo sapiens 63-67 24877179-0 2014 Nebivolol potentiates the efficacy of PDE5 inhibitors to relax corpus cavernosum and penile arteries from diabetic patients by enhancing the NO/cGMP pathway. Cyclic GMP 144-148 phosphodiesterase 5A Homo sapiens 38-42 24877179-10 2014 Enhancement of relaxant capacity by nebivolol resulted in reversion of the impairment of PDE5 inhibition-induced responses in DMED and it was accompanied by enhancing the ability of PDE5 inhibitors to increase cGMP in HCC restoring reduced cGMP levelsin HCC from DMED. Cyclic GMP 210-214 phosphodiesterase 5A Homo sapiens 182-186 23909451-0 2014 Decreasing phosphodiesterase 5A activity contributes to platelet cGMP accumulation during storage of apheresis-derived platelet concentrates. Cyclic GMP 65-69 phosphodiesterase 5A Homo sapiens 11-31 23909451-12 2014 CONCLUSION: Storage of APCs leads to intracellular cGMP accumulation that could be caused by degradation of PDE5A. Cyclic GMP 51-55 phosphodiesterase 5A Homo sapiens 108-113 24177060-4 2013 Phosphodiesterase 5 (PDE5) is an enzyme responsible for cGMP inactivation, and the use of its inhibitors can be an alternative in the search of a more balanced adipose tissue. Cyclic GMP 56-60 phosphodiesterase 5A Homo sapiens 0-19 24177060-4 2013 Phosphodiesterase 5 (PDE5) is an enzyme responsible for cGMP inactivation, and the use of its inhibitors can be an alternative in the search of a more balanced adipose tissue. Cyclic GMP 56-60 phosphodiesterase 5A Homo sapiens 21-25 24432631-1 2013 The enzyme phosphodiesterase-5 (PDE-5), widely distributed in the heart, smooth muscle, and blood vessels, catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator, and is also a nitric oxide (NO) donor. Cyclic GMP 135-165 phosphodiesterase 5A Homo sapiens 11-30 24432631-1 2013 The enzyme phosphodiesterase-5 (PDE-5), widely distributed in the heart, smooth muscle, and blood vessels, catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator, and is also a nitric oxide (NO) donor. Cyclic GMP 135-165 phosphodiesterase 5A Homo sapiens 32-37 24432631-1 2013 The enzyme phosphodiesterase-5 (PDE-5), widely distributed in the heart, smooth muscle, and blood vessels, catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator, and is also a nitric oxide (NO) donor. Cyclic GMP 167-171 phosphodiesterase 5A Homo sapiens 11-30 24432631-1 2013 The enzyme phosphodiesterase-5 (PDE-5), widely distributed in the heart, smooth muscle, and blood vessels, catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator, and is also a nitric oxide (NO) donor. Cyclic GMP 167-171 phosphodiesterase 5A Homo sapiens 32-37 24877179-10 2014 Enhancement of relaxant capacity by nebivolol resulted in reversion of the impairment of PDE5 inhibition-induced responses in DMED and it was accompanied by enhancing the ability of PDE5 inhibitors to increase cGMP in HCC restoring reduced cGMP levelsin HCC from DMED. Cyclic GMP 240-244 phosphodiesterase 5A Homo sapiens 182-186 24877179-11 2014 CONCLUSIONS: Nebivolol potentiated the capacity of PDE5 inhibitors to relax vascular structures of erectile tissue from diabetic patients by enhancing the nitric oxide (NO)/cGMP pathway in these tissues. Cyclic GMP 173-177 phosphodiesterase 5A Homo sapiens 51-55 25051133-2 2014 PDE5 inhibitors can induce vasodilation; in addition, through a complex pathway involving nitric oxide, cyclic guanosine monophosphate, and protein kinase G, it can reduce apoptosis and suppress cell proliferation. Cyclic GMP 104-134 phosphodiesterase 5A Homo sapiens 0-4 24550991-2 2014 Phosphodiesterase 5 (PDE5) specifically degrades cGMP and is highly abundant in the mammalian brain. Cyclic GMP 49-53 phosphodiesterase 5A Homo sapiens 0-19 24550991-2 2014 Phosphodiesterase 5 (PDE5) specifically degrades cGMP and is highly abundant in the mammalian brain. Cyclic GMP 49-53 phosphodiesterase 5A Homo sapiens 21-25 24550991-3 2014 Inhibition of cGMP hydrolysis by blocking PDE5 is a possible strategy to enhance the first step of neurogenesis, proliferation of neural stem cells (NSC). Cyclic GMP 14-18 phosphodiesterase 5A Homo sapiens 42-46 23925396-4 2013 Sildenafil citrate inhibits type 5-specific phosphodiesterase (PDE5), thus preventing the degradation of cyclic guanosine monophosphate (cGMP) in the muscle and augmenting the vasodilatory effects of NO. Cyclic GMP 137-141 phosphodiesterase 5A Homo sapiens 63-67 24259695-6 2013 DATA SYNTHESIS: Avanafil is a highly selective PDE5 inhibitor that is a competitive antagonist of cyclic guanosine monophosphate. Cyclic GMP 98-128 phosphodiesterase 5A Homo sapiens 47-51 23804703-5 2013 Knockdown of the cGMP-specific PDE5 isozyme by siRNA and PDE5-specific inhibitors tadalafil and sildenafil also selectively inhibited the growth of colon tumor cells that expressed high levels of PDE5 compared with colonocytes. Cyclic GMP 17-21 phosphodiesterase 5A Homo sapiens 31-35 23917809-1 2013 Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). Cyclic GMP 119-149 phosphodiesterase 5A Homo sapiens 0-19 23917809-1 2013 Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). Cyclic GMP 119-149 phosphodiesterase 5A Homo sapiens 21-26 23917809-1 2013 Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). Cyclic GMP 119-149 phosphodiesterase 5A Homo sapiens 78-83 23917809-1 2013 Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). Cyclic GMP 151-155 phosphodiesterase 5A Homo sapiens 0-19 23917809-1 2013 Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). Cyclic GMP 151-155 phosphodiesterase 5A Homo sapiens 21-26 23917809-1 2013 Phosphodiesterase 5 (PDE 5) inhibitors are selective inhibitors of the enzyme PDE 5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator and nitric oxide (NO) donor, to its corresponding metabolites (monophosphates). Cyclic GMP 151-155 phosphodiesterase 5A Homo sapiens 78-83 23916810-4 2013 We also observed that a major cGMP negative regulator, phosphodiesterase 5, was overexpressed in AML cells, and PDE5 inhibitor, an anti-erectile dysfunction drug, synergistically enhanced the anti-AML effect of EGCG. Cyclic GMP 30-34 phosphodiesterase 5A Homo sapiens 112-116 23758451-1 2013 Sildenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE-5). Cyclic GMP 39-69 phosphodiesterase 5A Homo sapiens 112-117 23758451-1 2013 Sildenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE-5). Cyclic GMP 71-75 phosphodiesterase 5A Homo sapiens 112-117 23986226-4 2013 Within this pathway, cAMP levels are regulated by phosphodiesterase 3 (PDE3), a PDE that is inhibited by cGMP, a cyclic nucleotide regulated by the activity of PDE5. Cyclic GMP 105-109 phosphodiesterase 5A Homo sapiens 160-164 23804703-5 2013 Knockdown of the cGMP-specific PDE5 isozyme by siRNA and PDE5-specific inhibitors tadalafil and sildenafil also selectively inhibited the growth of colon tumor cells that expressed high levels of PDE5 compared with colonocytes. Cyclic GMP 17-21 phosphodiesterase 5A Homo sapiens 57-61 23804703-5 2013 Knockdown of the cGMP-specific PDE5 isozyme by siRNA and PDE5-specific inhibitors tadalafil and sildenafil also selectively inhibited the growth of colon tumor cells that expressed high levels of PDE5 compared with colonocytes. Cyclic GMP 17-21 phosphodiesterase 5A Homo sapiens 57-61 23441682-5 2013 KEY RESULTS: Concentration-dependent vasodilation to the PDE5 inhibitor, sildenafil, in HPRA was sensitive to endothelium removal, NO/cGMP pathway inhibition and KCa blockade. Cyclic GMP 134-138 phosphodiesterase 5A Homo sapiens 57-61 23961322-4 2013 It is now evident that the vascular production of cGMP can be augmented by inhibitors of phosphodiesterase type 5 (PDE 5), the enzyme which breakdowns this cyclic nucleotide. Cyclic GMP 50-54 phosphodiesterase 5A Homo sapiens 89-113 23961322-4 2013 It is now evident that the vascular production of cGMP can be augmented by inhibitors of phosphodiesterase type 5 (PDE 5), the enzyme which breakdowns this cyclic nucleotide. Cyclic GMP 50-54 phosphodiesterase 5A Homo sapiens 115-120 23873899-6 2013 The cGMP-phosphodiesterase 5 (PDE5) pathway is one of the extensively studied pathways in PAH, but our knowledge about cGMP-PDE5 signalling in RV pathophysiology is still limited. Cyclic GMP 4-8 phosphodiesterase 5A Homo sapiens 30-34 23873899-9 2013 In this report, we discuss myocardial regulatory effects of cGMP-PDE5 signalling in preclinical models of RV pressure overload for understanding the physiological/pathophysiological mechanisms involved in maladaptive RVH. Cyclic GMP 60-64 phosphodiesterase 5A Homo sapiens 65-69 23597052-4 2013 AREAS COVERED: This review will mainly cover the effect of NO donors, which produce NO, and PDE5 inhibitors, which elevate cyclic guanosine 3",5"-monophosphate (cGMP), on neural restorative events in ischemic brain and highlight mechanisms underlying their restorative therapeutic activity. Cyclic GMP 123-159 phosphodiesterase 5A Homo sapiens 92-96 23597052-4 2013 AREAS COVERED: This review will mainly cover the effect of NO donors, which produce NO, and PDE5 inhibitors, which elevate cyclic guanosine 3",5"-monophosphate (cGMP), on neural restorative events in ischemic brain and highlight mechanisms underlying their restorative therapeutic activity. Cyclic GMP 161-165 phosphodiesterase 5A Homo sapiens 92-96 23597052-7 2013 Preclinical data suggest that elevated cGMP levels induced by NO donors and PDE5 inhibitors act on cerebral endothelial cells, neural stem cells and oligodendrocyte progenitor cells to enhance stroke-induced angiogenesis, neurogenesis and oligodendrogenesis, respectively. Cyclic GMP 39-43 phosphodiesterase 5A Homo sapiens 76-80 23888186-2 2013 Common pathophysiolgical mechanisms underlying both LUTS/BPH and ED, including alteration of NO/cGMP or RhoA/Rho-kinase signaling and/or vascular or neurogenic dysfunction, are potential targets for proposed phosphodiesterase type 5 inhibitors (PDE5-Is). Cyclic GMP 96-100 phosphodiesterase 5A Homo sapiens 245-249 23421435-4 2013 : To assess changes in the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase (PKG) pathway in human corpus cavernosum (HCC) of PDE5-i nonresponders compared with healthy controls. Cyclic GMP 45-75 phosphodiesterase 5A Homo sapiens 148-152 23421435-4 2013 : To assess changes in the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase (PKG) pathway in human corpus cavernosum (HCC) of PDE5-i nonresponders compared with healthy controls. Cyclic GMP 77-81 phosphodiesterase 5A Homo sapiens 148-152 23764893-3 2013 The intracellular cGMP levels are regulated by its hydrolysis via phosphodiesterase 5 (PDE5) and efflux via novel multidrug resistance protein 5 (MRP5). Cyclic GMP 18-22 phosphodiesterase 5A Homo sapiens 66-85 23764893-3 2013 The intracellular cGMP levels are regulated by its hydrolysis via phosphodiesterase 5 (PDE5) and efflux via novel multidrug resistance protein 5 (MRP5). Cyclic GMP 18-22 phosphodiesterase 5A Homo sapiens 87-91 23421435-12 2013 RESULTS: The main targets in the NO/cGMP/sGC pathway were downregulated in PDE5-i nonresponders. Cyclic GMP 36-40 phosphodiesterase 5A Homo sapiens 75-79 23382484-2 2013 Phosphodiesterase type 5 (PDE5) inhibitors prolong nitric oxide-mediated cyclic guanosine monophosphate (cGMP) signaling in vascular smooth muscle, and have beneficial effects on exercise tolerance in pulmonary hypertension and heart failure. Cyclic GMP 73-103 phosphodiesterase 5A Homo sapiens 0-24 23678721-2 2013 PDE5 inhibiter can competitively inhibit the hydrolysis of cyclic guanosine monophosphate (cGMP), increase the cGMP concentration in the smooth muscle cells of the corpus cavernosum penis, and achieve the therapeutic effect on ED. Cyclic GMP 59-89 phosphodiesterase 5A Homo sapiens 0-4 23678721-2 2013 PDE5 inhibiter can competitively inhibit the hydrolysis of cyclic guanosine monophosphate (cGMP), increase the cGMP concentration in the smooth muscle cells of the corpus cavernosum penis, and achieve the therapeutic effect on ED. Cyclic GMP 91-95 phosphodiesterase 5A Homo sapiens 0-4 23678721-2 2013 PDE5 inhibiter can competitively inhibit the hydrolysis of cyclic guanosine monophosphate (cGMP), increase the cGMP concentration in the smooth muscle cells of the corpus cavernosum penis, and achieve the therapeutic effect on ED. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 0-4 22383129-9 2013 RESULTS: PDE5 and PDE11 were the most prominent PDEs in the cell lines, representing between 86 and 95% of the total cGMP-specific PDE activity. Cyclic GMP 117-121 phosphodiesterase 5A Homo sapiens 9-13 23382484-2 2013 Phosphodiesterase type 5 (PDE5) inhibitors prolong nitric oxide-mediated cyclic guanosine monophosphate (cGMP) signaling in vascular smooth muscle, and have beneficial effects on exercise tolerance in pulmonary hypertension and heart failure. Cyclic GMP 73-103 phosphodiesterase 5A Homo sapiens 26-30 23382484-2 2013 Phosphodiesterase type 5 (PDE5) inhibitors prolong nitric oxide-mediated cyclic guanosine monophosphate (cGMP) signaling in vascular smooth muscle, and have beneficial effects on exercise tolerance in pulmonary hypertension and heart failure. Cyclic GMP 105-109 phosphodiesterase 5A Homo sapiens 0-24 23382484-2 2013 Phosphodiesterase type 5 (PDE5) inhibitors prolong nitric oxide-mediated cyclic guanosine monophosphate (cGMP) signaling in vascular smooth muscle, and have beneficial effects on exercise tolerance in pulmonary hypertension and heart failure. Cyclic GMP 105-109 phosphodiesterase 5A Homo sapiens 26-30 23114592-2 2013 Increasing the availability of cyclic guanosine monophosphate (cGMP) by inhibition of phosphodiesterase-5 (PDE5) is a relatively new, but promising therapeutic strategy. Cyclic GMP 31-61 phosphodiesterase 5A Homo sapiens 86-105 23018163-7 2013 In vitro assays have demonstrated PDE5-Is by regulating cyclic guanosine monophosphate (cGMP) degradation and enhancing the nitric oxide/cGMP signaling pathway to relax human smooth muscle strips from the prostate, bladder, and LUT arteries. Cyclic GMP 56-86 phosphodiesterase 5A Homo sapiens 34-38 23018163-7 2013 In vitro assays have demonstrated PDE5-Is by regulating cyclic guanosine monophosphate (cGMP) degradation and enhancing the nitric oxide/cGMP signaling pathway to relax human smooth muscle strips from the prostate, bladder, and LUT arteries. Cyclic GMP 88-92 phosphodiesterase 5A Homo sapiens 34-38 23018163-7 2013 In vitro assays have demonstrated PDE5-Is by regulating cyclic guanosine monophosphate (cGMP) degradation and enhancing the nitric oxide/cGMP signaling pathway to relax human smooth muscle strips from the prostate, bladder, and LUT arteries. Cyclic GMP 137-141 phosphodiesterase 5A Homo sapiens 34-38 23114592-2 2013 Increasing the availability of cyclic guanosine monophosphate (cGMP) by inhibition of phosphodiesterase-5 (PDE5) is a relatively new, but promising therapeutic strategy. Cyclic GMP 31-61 phosphodiesterase 5A Homo sapiens 107-111 23114592-2 2013 Increasing the availability of cyclic guanosine monophosphate (cGMP) by inhibition of phosphodiesterase-5 (PDE5) is a relatively new, but promising therapeutic strategy. Cyclic GMP 63-67 phosphodiesterase 5A Homo sapiens 86-105 23114592-2 2013 Increasing the availability of cyclic guanosine monophosphate (cGMP) by inhibition of phosphodiesterase-5 (PDE5) is a relatively new, but promising therapeutic strategy. Cyclic GMP 63-67 phosphodiesterase 5A Homo sapiens 107-111 22947364-1 2012 Phosphodiesterase 5 (PDE-5) inhibitors are selective blockers of PDE-5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP) to its corresponding monophosphates. Cyclic GMP 106-136 phosphodiesterase 5A Homo sapiens 0-19 23372609-1 2013 Orally active, selective inhibitors of phosphodiesterase type 5 (PDE 5, cyclic GMP PDE), such as sildenafil, tadalafil and vardenafil, are currently the first-choice treatment options for the clinical management of erectile dysfunction (ED) of various etiologies and severities. Cyclic GMP 72-82 phosphodiesterase 5A Homo sapiens 39-63 23307609-4 2013 Compound 8 was the most potent PDE5 inhibitor and showed selectivity towards PDE5 versus other PDEs, with a selectivity index of 49 towards PDE5 rather than PDE11 with cGMP as the substrate. Cyclic GMP 168-172 phosphodiesterase 5A Homo sapiens 77-81 23307609-4 2013 Compound 8 was the most potent PDE5 inhibitor and showed selectivity towards PDE5 versus other PDEs, with a selectivity index of 49 towards PDE5 rather than PDE11 with cGMP as the substrate. Cyclic GMP 168-172 phosphodiesterase 5A Homo sapiens 77-81 24092343-4 2013 In the pulmonary vasculature, degradation of cGMP is primarily regulated by PDE-5, and inhibition of this enzyme has important effects on pulmonary vasculature smooth muscle tone. Cyclic GMP 45-49 phosphodiesterase 5A Homo sapiens 76-81 23709025-6 2013 PDE5, PDE6, and PDE9 are considered to be cGMP specific, while PDE1, PDE2, PDE3, PDE10, and PDE11 can hydrolyze both cGMP and cAMP. Cyclic GMP 42-46 phosphodiesterase 5A Homo sapiens 0-4 23709025-6 2013 PDE5, PDE6, and PDE9 are considered to be cGMP specific, while PDE1, PDE2, PDE3, PDE10, and PDE11 can hydrolyze both cGMP and cAMP. Cyclic GMP 117-121 phosphodiesterase 5A Homo sapiens 0-4 23709027-3 2013 The probes are comprised of known cGMP binding sites-e.g., from phosphodiesterase type 5 (PDE5) or protein kinase G (PKG)-attached to fluorescent proteins. Cyclic GMP 34-38 phosphodiesterase 5A Homo sapiens 64-88 23709027-3 2013 The probes are comprised of known cGMP binding sites-e.g., from phosphodiesterase type 5 (PDE5) or protein kinase G (PKG)-attached to fluorescent proteins. Cyclic GMP 34-38 phosphodiesterase 5A Homo sapiens 90-94 23086989-2 2012 We tested the hypothesis that melatonin increases the phosphorylation of phosphodiesterase 5 (PDE5), which increases the activity of the enzyme and thereby decreases intracellular cGMP accumulation in response to NO and inhibits NO-induced relaxation. Cyclic GMP 180-184 phosphodiesterase 5A Homo sapiens 73-92 23086989-2 2012 We tested the hypothesis that melatonin increases the phosphorylation of phosphodiesterase 5 (PDE5), which increases the activity of the enzyme and thereby decreases intracellular cGMP accumulation in response to NO and inhibits NO-induced relaxation. Cyclic GMP 180-184 phosphodiesterase 5A Homo sapiens 94-98 23086989-7 2012 Treatment of coronary arteries with melatonin caused a nearly fourfold increase in the phosphorylation of PDE5, which increased the catalytic activity of the enzyme and thereby increased the degradation of cGMP to inactive 5"-GMP. Cyclic GMP 206-210 phosphodiesterase 5A Homo sapiens 106-110 23086989-8 2012 Melatonin-induced PDE5 phosphorylation was markedly attenuated in the presence of the PKG1 inhibitors DT-2 or Rp-8-Br-PET-cGMPS and in those arteries in which PKG1 expression was first downregulated by 24-h incubation with SNP before exposure to melatonin. Cyclic GMP 122-127 phosphodiesterase 5A Homo sapiens 18-22 23197572-8 2012 In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3",5"-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. Cyclic GMP 209-238 phosphodiesterase 5A Homo sapiens 294-314 22948216-6 2012 Enhancement of nitric oxide/cyclic guanosine monophosphate signaling by vardenafil, sodium nitroprusside, or PDE5 knockdown reduced smooth muscle cell actin and IGF binding protein 3 mRNA and protein levels and restored fibroblast-like morphology in trans-differentiated myofibroblast. Cyclic GMP 28-58 phosphodiesterase 5A Homo sapiens 109-113 22948216-10 2012 Thus, enhancement of the nitric oxide/cyclic guanosine monophosphate signaling pathway by vardenafil attenuates and reverts fibroblast-to-myofibroblast trans-differentiation, hypothesizing that BPH patients might benefit from long-term therapy with PDE5 inhibitors. Cyclic GMP 38-68 phosphodiesterase 5A Homo sapiens 249-253 23417046-2 2013 These PDE5 inhibitors are known to increase cyclic guanosine monophosphate (cGMP) concentrations in the smooth muscle cells of the corpora cavernosa penis by inhibiting PDE5, leading to smooth muscle relaxation. Cyclic GMP 44-74 phosphodiesterase 5A Homo sapiens 6-10 23417046-2 2013 These PDE5 inhibitors are known to increase cyclic guanosine monophosphate (cGMP) concentrations in the smooth muscle cells of the corpora cavernosa penis by inhibiting PDE5, leading to smooth muscle relaxation. Cyclic GMP 44-74 phosphodiesterase 5A Homo sapiens 169-173 23417046-2 2013 These PDE5 inhibitors are known to increase cyclic guanosine monophosphate (cGMP) concentrations in the smooth muscle cells of the corpora cavernosa penis by inhibiting PDE5, leading to smooth muscle relaxation. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 6-10 23417046-2 2013 These PDE5 inhibitors are known to increase cyclic guanosine monophosphate (cGMP) concentrations in the smooth muscle cells of the corpora cavernosa penis by inhibiting PDE5, leading to smooth muscle relaxation. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 169-173 23353150-6 2013 Pretreatment of the cells with Cyclosporine blocked the effects of ET-1, and PDE5 inhibition by sildenafil pretreatment also abolished ET-1-induced reduction of cGMP level in the cells. Cyclic GMP 161-165 phosphodiesterase 5A Homo sapiens 77-81 23353150-8 2013 CONCLUSION: Activation of calcineurin/NFAT signaling pathway mediates ET-1-induced PASMC proliferation by stimulating PDE5 expression, which further degrades cGMP. Cyclic GMP 158-162 phosphodiesterase 5A Homo sapiens 118-122 24146440-8 2013 PDE5, which specifically hydrolyses cGMP and which mainly contributes to cGMP hydrolysis is also potently inhibited by ALF (IC50=7.6 +- 3.5 microg/ml). Cyclic GMP 36-40 phosphodiesterase 5A Homo sapiens 0-4 24146440-8 2013 PDE5, which specifically hydrolyses cGMP and which mainly contributes to cGMP hydrolysis is also potently inhibited by ALF (IC50=7.6 +- 3.5 microg/ml). Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 0-4 22798047-3 2012 The latter is regulated by members of the phosphodiesterase (PDE) superfamily, of which cGMP-selective PDE5 has been best studied. Cyclic GMP 88-92 phosphodiesterase 5A Homo sapiens 103-107 22947364-1 2012 Phosphodiesterase 5 (PDE-5) inhibitors are selective blockers of PDE-5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP) to its corresponding monophosphates. Cyclic GMP 106-136 phosphodiesterase 5A Homo sapiens 21-26 22947364-1 2012 Phosphodiesterase 5 (PDE-5) inhibitors are selective blockers of PDE-5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP) to its corresponding monophosphates. Cyclic GMP 106-136 phosphodiesterase 5A Homo sapiens 65-70 22947364-1 2012 Phosphodiesterase 5 (PDE-5) inhibitors are selective blockers of PDE-5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP) to its corresponding monophosphates. Cyclic GMP 138-142 phosphodiesterase 5A Homo sapiens 0-19 22947364-1 2012 Phosphodiesterase 5 (PDE-5) inhibitors are selective blockers of PDE-5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP) to its corresponding monophosphates. Cyclic GMP 138-142 phosphodiesterase 5A Homo sapiens 21-26 22947364-1 2012 Phosphodiesterase 5 (PDE-5) inhibitors are selective blockers of PDE-5, which catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP) to its corresponding monophosphates. Cyclic GMP 138-142 phosphodiesterase 5A Homo sapiens 65-70 21996373-3 2012 Sildenafil inhibits the cGMP-hydrolyzing PDE5 and thereby promotes relaxation of smooth muscle cells. Cyclic GMP 24-28 phosphodiesterase 5A Homo sapiens 41-45 22875455-2 2012 cGMP hydrolysis by several members of the phosphodiesterase (PDE) superfamily, PDE1, PDE2, and PDE5, regulate this signaling in the heart. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 95-99 22556201-3 2012 The basis for this activity appears to involve cyclic guanosine 3",5",-monophosphate phosphodiesterase (cGMP PDE) inhibition as evident by its ability to inhibit cGMP hydrolysis in colon tumor cell lysates and purified cGMP-specific PDE5, increase intracellular cGMP levels, and activate cGMP-dependent protein kinase G at concentrations that suppress tumor cell growth. Cyclic GMP 104-108 phosphodiesterase 5A Homo sapiens 233-237 22556201-3 2012 The basis for this activity appears to involve cyclic guanosine 3",5",-monophosphate phosphodiesterase (cGMP PDE) inhibition as evident by its ability to inhibit cGMP hydrolysis in colon tumor cell lysates and purified cGMP-specific PDE5, increase intracellular cGMP levels, and activate cGMP-dependent protein kinase G at concentrations that suppress tumor cell growth. Cyclic GMP 162-166 phosphodiesterase 5A Homo sapiens 233-237 22556201-3 2012 The basis for this activity appears to involve cyclic guanosine 3",5",-monophosphate phosphodiesterase (cGMP PDE) inhibition as evident by its ability to inhibit cGMP hydrolysis in colon tumor cell lysates and purified cGMP-specific PDE5, increase intracellular cGMP levels, and activate cGMP-dependent protein kinase G at concentrations that suppress tumor cell growth. Cyclic GMP 162-166 phosphodiesterase 5A Homo sapiens 233-237 22556201-3 2012 The basis for this activity appears to involve cyclic guanosine 3",5",-monophosphate phosphodiesterase (cGMP PDE) inhibition as evident by its ability to inhibit cGMP hydrolysis in colon tumor cell lysates and purified cGMP-specific PDE5, increase intracellular cGMP levels, and activate cGMP-dependent protein kinase G at concentrations that suppress tumor cell growth. Cyclic GMP 162-166 phosphodiesterase 5A Homo sapiens 233-237 22556201-7 2012 We conclude that PDE5 and possibly other cGMP degrading isozymes can be targeted to develop safer and more efficacious NSAID derivatives for colorectal cancer chemoprevention. Cyclic GMP 41-45 phosphodiesterase 5A Homo sapiens 17-21 22261303-7 2012 KEY FINDINGS: The presence and activity of PDE5 were confirmed in ventricular cardiomyocytes from failing and hypertrophied human heart, as well as PDE3, with ventricle-specific results for PDE4 and a surprisingly large contribution from PDE1 for hydrolysis of both cAMP and cGMP. Cyclic GMP 275-279 phosphodiesterase 5A Homo sapiens 43-47 22514270-6 2012 Whereas the closely related PDE5 homodimer undergoes a significant change in its sedimentation properties upon cGMP binding to its regulatory cGMP binding site, no such change was detected upon ligand binding to the PDE6 catalytic dimer. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 28-32 22514270-6 2012 Whereas the closely related PDE5 homodimer undergoes a significant change in its sedimentation properties upon cGMP binding to its regulatory cGMP binding site, no such change was detected upon ligand binding to the PDE6 catalytic dimer. Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 28-32 22426465-1 2012 A promising target for memory improvement is phosphodiesterase type 5 (PDE5), which selectively hydrolyzes cyclic guanosine monophosphate (cGMP). Cyclic GMP 107-137 phosphodiesterase 5A Homo sapiens 45-69 22426465-1 2012 A promising target for memory improvement is phosphodiesterase type 5 (PDE5), which selectively hydrolyzes cyclic guanosine monophosphate (cGMP). Cyclic GMP 107-137 phosphodiesterase 5A Homo sapiens 71-75 22426465-1 2012 A promising target for memory improvement is phosphodiesterase type 5 (PDE5), which selectively hydrolyzes cyclic guanosine monophosphate (cGMP). Cyclic GMP 139-143 phosphodiesterase 5A Homo sapiens 45-69 22426465-1 2012 A promising target for memory improvement is phosphodiesterase type 5 (PDE5), which selectively hydrolyzes cyclic guanosine monophosphate (cGMP). Cyclic GMP 139-143 phosphodiesterase 5A Homo sapiens 71-75 22080917-2 2012 In PDE5, the GAF-A subdomain of a GAF-tandem (GAF-A and -B) binds the activator cGMP and in PDE10 GAF-B binds cAMP. Cyclic GMP 80-84 phosphodiesterase 5A Homo sapiens 3-7 26676704-9 2012 PDE5 inhibitors increase the concentration of cyclic guanosine monophosphate (cGMP) in plasma and smooth muscle, promoting erection of the penis, as well as relaxation of the bladder neck and prostate, leading to natural voiding. Cyclic GMP 46-76 phosphodiesterase 5A Homo sapiens 0-4 26676704-9 2012 PDE5 inhibitors increase the concentration of cyclic guanosine monophosphate (cGMP) in plasma and smooth muscle, promoting erection of the penis, as well as relaxation of the bladder neck and prostate, leading to natural voiding. Cyclic GMP 78-82 phosphodiesterase 5A Homo sapiens 0-4 22474995-0 2012 [Chinese herbal drugs for erectile dysfunction through NO-cGMP-PDE5 signaling pathway]. Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 63-67 22474995-2 2012 NO-cGMP-PDE5 signaling pathway plays an important role in regulating the relaxation of corpus cavernosum smooth muscle, and its relevant studies have contributed greatly to the clinical treatment of ED. Cyclic GMP 3-7 phosphodiesterase 5A Homo sapiens 8-12 22474995-3 2012 Chinese herbal drugs have long been used in the treatment of ED, and the action mechanisms of some of them clarified through the NO-cGMP-PDE5 signaling pathway. Cyclic GMP 132-136 phosphodiesterase 5A Homo sapiens 137-141 21996373-9 2012 Data demonstrate that PDE5 is an important member of cGMP signaling pathways regulating the finely orchestrated process of epididymal duct contractility and suggest, however, that in the epididymis side effects of therapeutically used sildenafil are unlikely. Cyclic GMP 53-57 phosphodiesterase 5A Homo sapiens 22-26 22105073-2 2012 In PDE2 and PDE5, the GAF domains mediate cGMP stimulation; however, their function in PDE10 and PDE11 remains controversial. Cyclic GMP 42-46 phosphodiesterase 5A Homo sapiens 12-16 21649691-5 2011 Platelets possess three PDE isoforms (PDE2, PDE3 and PDE5), with different selectivity for cAMP and cGMP. Cyclic GMP 100-104 phosphodiesterase 5A Homo sapiens 53-57 22918733-4 2012 Platelets possess several PDEs (PDE2, PDE3 and PDE5) that catalyze the hydrolysis of cyclic adenosine 3"-5"-monophosphate (cAMP) and cyclic guanosine 3"-5"-monophosphate (cGMP), thereby limiting the levels of intracellular nucleotides. Cyclic GMP 133-169 phosphodiesterase 5A Homo sapiens 47-51 22918733-4 2012 Platelets possess several PDEs (PDE2, PDE3 and PDE5) that catalyze the hydrolysis of cyclic adenosine 3"-5"-monophosphate (cAMP) and cyclic guanosine 3"-5"-monophosphate (cGMP), thereby limiting the levels of intracellular nucleotides. Cyclic GMP 171-175 phosphodiesterase 5A Homo sapiens 47-51 22234177-3 2011 AT harbors the whole molecular signaling pathway of NO, together with type 5-phosphodiesterase (PDE- 5), the main cGMP catabolising enzyme. Cyclic GMP 114-118 phosphodiesterase 5A Homo sapiens 96-102 21620965-0 2011 Conformational conversion of PDE5 by incubation with sildenafil or metal ion is accompanied by stimulation of allosteric cGMP binding. Cyclic GMP 121-125 phosphodiesterase 5A Homo sapiens 29-33 21620965-1 2011 Phosphodiesterase-5 (PDE5) is a dimer containing a cGMP-specific catalytic domain and an allosteric cGMP-binding subdomain (GAF A) on each subunit. Cyclic GMP 51-55 phosphodiesterase 5A Homo sapiens 0-19 21620965-1 2011 Phosphodiesterase-5 (PDE5) is a dimer containing a cGMP-specific catalytic domain and an allosteric cGMP-binding subdomain (GAF A) on each subunit. Cyclic GMP 51-55 phosphodiesterase 5A Homo sapiens 21-25 21620965-1 2011 Phosphodiesterase-5 (PDE5) is a dimer containing a cGMP-specific catalytic domain and an allosteric cGMP-binding subdomain (GAF A) on each subunit. Cyclic GMP 100-104 phosphodiesterase 5A Homo sapiens 0-19 21620965-1 2011 Phosphodiesterase-5 (PDE5) is a dimer containing a cGMP-specific catalytic domain and an allosteric cGMP-binding subdomain (GAF A) on each subunit. Cyclic GMP 100-104 phosphodiesterase 5A Homo sapiens 21-25 21620965-3 2011 A preparation comprised mainly of Band 2 PDE5 was partially converted to Band 3 PDE5 by 1h incubation with cGMP or the PDE5-specific inhibitors sildenafil, vardenafil, or tadalafil, but not with cAMP, milrinone (PDE3-specific), or rolipram (PDE4-specific). Cyclic GMP 107-111 phosphodiesterase 5A Homo sapiens 41-45 21620965-3 2011 A preparation comprised mainly of Band 2 PDE5 was partially converted to Band 3 PDE5 by 1h incubation with cGMP or the PDE5-specific inhibitors sildenafil, vardenafil, or tadalafil, but not with cAMP, milrinone (PDE3-specific), or rolipram (PDE4-specific). Cyclic GMP 107-111 phosphodiesterase 5A Homo sapiens 80-84 21620965-3 2011 A preparation comprised mainly of Band 2 PDE5 was partially converted to Band 3 PDE5 by 1h incubation with cGMP or the PDE5-specific inhibitors sildenafil, vardenafil, or tadalafil, but not with cAMP, milrinone (PDE3-specific), or rolipram (PDE4-specific). Cyclic GMP 107-111 phosphodiesterase 5A Homo sapiens 80-84 22785374-5 2012 Among several cGMP-PDEs, cGMP-specific PDE5 has been intensively investigated. Cyclic GMP 14-18 phosphodiesterase 5A Homo sapiens 39-43 22785374-5 2012 Among several cGMP-PDEs, cGMP-specific PDE5 has been intensively investigated. Cyclic GMP 25-29 phosphodiesterase 5A Homo sapiens 39-43 21987443-7 2011 Treatment of L-1236 with PDE5A-inhibitor sildenafil or with siRNA directed against PDE5A and concomitant stimulation with cyclic guanosine monophosphate (cGMP) resulted in enhanced apoptosis, indicating PDE5A as an oncogene. Cyclic GMP 154-158 phosphodiesterase 5A Homo sapiens 25-30 21620965-4 2011 Band 2 PDE5 was converted almost entirely to Band 3 PDE5 by overnight incubation with sildenafil at 30 C. This time-dependent conversion was accompanied by a 7-fold increase in allosteric cGMP-binding activity, suggesting that Band 3 PDE5 is a much more active form than Band 2 PDE5 for allosteric cGMP binding. Cyclic GMP 188-192 phosphodiesterase 5A Homo sapiens 7-11 21620965-4 2011 Band 2 PDE5 was converted almost entirely to Band 3 PDE5 by overnight incubation with sildenafil at 30 C. This time-dependent conversion was accompanied by a 7-fold increase in allosteric cGMP-binding activity, suggesting that Band 3 PDE5 is a much more active form than Band 2 PDE5 for allosteric cGMP binding. Cyclic GMP 188-192 phosphodiesterase 5A Homo sapiens 52-56 21620965-4 2011 Band 2 PDE5 was converted almost entirely to Band 3 PDE5 by overnight incubation with sildenafil at 30 C. This time-dependent conversion was accompanied by a 7-fold increase in allosteric cGMP-binding activity, suggesting that Band 3 PDE5 is a much more active form than Band 2 PDE5 for allosteric cGMP binding. Cyclic GMP 188-192 phosphodiesterase 5A Homo sapiens 52-56 21620965-4 2011 Band 2 PDE5 was converted almost entirely to Band 3 PDE5 by overnight incubation with sildenafil at 30 C. This time-dependent conversion was accompanied by a 7-fold increase in allosteric cGMP-binding activity, suggesting that Band 3 PDE5 is a much more active form than Band 2 PDE5 for allosteric cGMP binding. Cyclic GMP 188-192 phosphodiesterase 5A Homo sapiens 52-56 21620965-4 2011 Band 2 PDE5 was converted almost entirely to Band 3 PDE5 by overnight incubation with sildenafil at 30 C. This time-dependent conversion was accompanied by a 7-fold increase in allosteric cGMP-binding activity, suggesting that Band 3 PDE5 is a much more active form than Band 2 PDE5 for allosteric cGMP binding. Cyclic GMP 298-302 phosphodiesterase 5A Homo sapiens 7-11 21620965-4 2011 Band 2 PDE5 was converted almost entirely to Band 3 PDE5 by overnight incubation with sildenafil at 30 C. This time-dependent conversion was accompanied by a 7-fold increase in allosteric cGMP-binding activity, suggesting that Band 3 PDE5 is a much more active form than Band 2 PDE5 for allosteric cGMP binding. Cyclic GMP 298-302 phosphodiesterase 5A Homo sapiens 52-56 21620965-4 2011 Band 2 PDE5 was converted almost entirely to Band 3 PDE5 by overnight incubation with sildenafil at 30 C. This time-dependent conversion was accompanied by a 7-fold increase in allosteric cGMP-binding activity, suggesting that Band 3 PDE5 is a much more active form than Band 2 PDE5 for allosteric cGMP binding. Cyclic GMP 298-302 phosphodiesterase 5A Homo sapiens 52-56 21620965-4 2011 Band 2 PDE5 was converted almost entirely to Band 3 PDE5 by overnight incubation with sildenafil at 30 C. This time-dependent conversion was accompanied by a 7-fold increase in allosteric cGMP-binding activity, suggesting that Band 3 PDE5 is a much more active form than Band 2 PDE5 for allosteric cGMP binding. Cyclic GMP 298-302 phosphodiesterase 5A Homo sapiens 52-56 21620965-5 2011 Conversion of Band 2 PDE5 to Band 3 PDE5 occurred faster by pre-incubation with cGMP, which binds to both the allosteric and catalytic sites of PDE5, than with catalytic site-specific sildenafil. Cyclic GMP 80-84 phosphodiesterase 5A Homo sapiens 21-25 21620965-5 2011 Conversion of Band 2 PDE5 to Band 3 PDE5 occurred faster by pre-incubation with cGMP, which binds to both the allosteric and catalytic sites of PDE5, than with catalytic site-specific sildenafil. Cyclic GMP 80-84 phosphodiesterase 5A Homo sapiens 36-40 21620965-5 2011 Conversion of Band 2 PDE5 to Band 3 PDE5 occurred faster by pre-incubation with cGMP, which binds to both the allosteric and catalytic sites of PDE5, than with catalytic site-specific sildenafil. Cyclic GMP 80-84 phosphodiesterase 5A Homo sapiens 36-40 21620965-6 2011 Overnight incubation of a Band 2/Band 3 PDE5 mixture with EDTA caused time-dependent conversion to Band 1 PDE5 (apoenzyme), and this conversion was accompanied by a 50% loss in cGMP-binding activity. Cyclic GMP 177-181 phosphodiesterase 5A Homo sapiens 40-44 21620965-6 2011 Overnight incubation of a Band 2/Band 3 PDE5 mixture with EDTA caused time-dependent conversion to Band 1 PDE5 (apoenzyme), and this conversion was accompanied by a 50% loss in cGMP-binding activity. Cyclic GMP 177-181 phosphodiesterase 5A Homo sapiens 106-110 21620965-9 2011 The combination of results implied that physiological conversion of Band 2 to Band 3 PDE5 by cGMP and/or divalent metal ion occupancy of the catalytic domain would increase allosteric cGMP binding to the enzyme. Cyclic GMP 93-97 phosphodiesterase 5A Homo sapiens 85-89 21620965-9 2011 The combination of results implied that physiological conversion of Band 2 to Band 3 PDE5 by cGMP and/or divalent metal ion occupancy of the catalytic domain would increase allosteric cGMP binding to the enzyme. Cyclic GMP 184-188 phosphodiesterase 5A Homo sapiens 85-89 21620965-10 2011 This conversion would produce a greater negative feedback effect on cGMP action by increasing sequestration of cGMP at the allosteric cGMP-binding site of PDE5 and by increasing cGMP degradation at the catalytic site of the enzyme. Cyclic GMP 68-72 phosphodiesterase 5A Homo sapiens 155-159 21620965-10 2011 This conversion would produce a greater negative feedback effect on cGMP action by increasing sequestration of cGMP at the allosteric cGMP-binding site of PDE5 and by increasing cGMP degradation at the catalytic site of the enzyme. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 155-159 21620965-10 2011 This conversion would produce a greater negative feedback effect on cGMP action by increasing sequestration of cGMP at the allosteric cGMP-binding site of PDE5 and by increasing cGMP degradation at the catalytic site of the enzyme. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 155-159 21620965-10 2011 This conversion would produce a greater negative feedback effect on cGMP action by increasing sequestration of cGMP at the allosteric cGMP-binding site of PDE5 and by increasing cGMP degradation at the catalytic site of the enzyme. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 155-159 21774742-1 2011 INTRODUCTION: At the present time, inhibitors of phosphodiesterase type 5 (PDE5) have Food and Drug Administration approval only for the treatment of erectile dysfunction and pulmonary artery hypertension, for which their mechanism of action is vasodilation and augmentation of blood flow by impeding PDE5-mediated breakdown of cyclic guanosine monophosphate. Cyclic GMP 328-358 phosphodiesterase 5A Homo sapiens 49-73 21774742-1 2011 INTRODUCTION: At the present time, inhibitors of phosphodiesterase type 5 (PDE5) have Food and Drug Administration approval only for the treatment of erectile dysfunction and pulmonary artery hypertension, for which their mechanism of action is vasodilation and augmentation of blood flow by impeding PDE5-mediated breakdown of cyclic guanosine monophosphate. Cyclic GMP 328-358 phosphodiesterase 5A Homo sapiens 75-79 21741267-1 2011 Phosphodiesterase type 5 (PDE5) is expressed in many tissues (e.g. heart, lung, pancreas, penis) and plays a specific role in hydrolyzing cyclic guanosine monophosphate (cGMP). Cyclic GMP 138-168 phosphodiesterase 5A Homo sapiens 0-24 21741267-1 2011 Phosphodiesterase type 5 (PDE5) is expressed in many tissues (e.g. heart, lung, pancreas, penis) and plays a specific role in hydrolyzing cyclic guanosine monophosphate (cGMP). Cyclic GMP 138-168 phosphodiesterase 5A Homo sapiens 26-30 21741267-1 2011 Phosphodiesterase type 5 (PDE5) is expressed in many tissues (e.g. heart, lung, pancreas, penis) and plays a specific role in hydrolyzing cyclic guanosine monophosphate (cGMP). Cyclic GMP 170-174 phosphodiesterase 5A Homo sapiens 0-24 21741267-1 2011 Phosphodiesterase type 5 (PDE5) is expressed in many tissues (e.g. heart, lung, pancreas, penis) and plays a specific role in hydrolyzing cyclic guanosine monophosphate (cGMP). Cyclic GMP 170-174 phosphodiesterase 5A Homo sapiens 26-30 21741267-5 2011 This review summarizes evidence supporting a role for the PDE5-regulated cGMP/PKG system in adipose tissue and its effects on adipocyte function. Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 58-62 21525805-3 2011 Here we establish the presence of cytosolic PDEs in RBCs and determine a role for PDE5 in regulating levels of cGMP. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 82-86 21790969-5 2011 Although patients with severe PH secondary to HF have not derived benefit from pulmonary arterial hypertension therapies thus far, agents that modulate the cyclic guanosine monophosphate pathway, including phosphodiesterase 5A inhibitors, hold promise and are being actively investigated in advanced HF. Cyclic GMP 156-186 phosphodiesterase 5A Homo sapiens 206-226 20803229-0 2011 Vardenafil, an inhibitor of phosphodiesterase-5, blocks advanced glycation end product (AGE)-induced up-regulation of monocyte chemoattractant protein-1 mRNA levels in endothelial cells by suppressing AGE receptor (RAGE) expression via elevation of cGMP. Cyclic GMP 249-253 phosphodiesterase 5A Homo sapiens 28-47 20803229-3 2011 However, effects of inhibitors of phosphodiesterase-5 (PDE-5), an enzyme that catalyzes the degradation of cyclic guanosin-monophosphate (cGMP) and subsequently blocks the actions of NO, on AGE-exposed endothelial cells remain unknown. Cyclic GMP 138-142 phosphodiesterase 5A Homo sapiens 34-53 20803229-3 2011 However, effects of inhibitors of phosphodiesterase-5 (PDE-5), an enzyme that catalyzes the degradation of cyclic guanosin-monophosphate (cGMP) and subsequently blocks the actions of NO, on AGE-exposed endothelial cells remain unknown. Cyclic GMP 138-142 phosphodiesterase 5A Homo sapiens 55-60 21702653-2 2011 The antipulmonary hypertensive effects of nitric oxide and the natriuretic peptides are mediated via increasing intracellular cGMP and enzymatic degradation by PDE-5 is the major route of cGMP inactivation in the lung. Cyclic GMP 188-192 phosphodiesterase 5A Homo sapiens 160-165 23391833-2 2011 We investigated the effect of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor that inhibits the breakdown of cyclic guanosine monophosphate (cGMP) resulting in vasodilatation, on the elasticity of HbSS erythrocyte. Cyclic GMP 112-142 phosphodiesterase 5A Homo sapiens 65-69 23391833-2 2011 We investigated the effect of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor that inhibits the breakdown of cyclic guanosine monophosphate (cGMP) resulting in vasodilatation, on the elasticity of HbSS erythrocyte. Cyclic GMP 144-148 phosphodiesterase 5A Homo sapiens 44-63 23391833-2 2011 We investigated the effect of sildenafil, a phosphodiesterase 5 (PDE5) inhibitor that inhibits the breakdown of cyclic guanosine monophosphate (cGMP) resulting in vasodilatation, on the elasticity of HbSS erythrocyte. Cyclic GMP 144-148 phosphodiesterase 5A Homo sapiens 65-69 21477871-4 2011 Inhibition of cGMP-targeted phosphodiesterases (PDEs) such as PDE5A is an alternative approach that appears to have more potent effects. Cyclic GMP 14-18 phosphodiesterase 5A Homo sapiens 62-67 21187142-0 2011 Metal ion stimulators of PDE5 cause similar conformational changes in the enzyme as does cGMP or sildenafil. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 25-29 21187142-2 2011 Treatment of recombinant or native PDE5 with either cGMP or a substrate analog such as sildenafil, each of which is known to produce stimulatory effects on enzyme functions, caused a similar native PAGE band-shift to the lower mobility form (shift of Band 2 to Band 3). Cyclic GMP 52-56 phosphodiesterase 5A Homo sapiens 35-39 21187142-3 2011 Incubation of PDE5 with Mg(++) or Mn(++), which is known to stimulate activity, caused a similar shift of the enzyme from Band 2 to Band 3 as did cGMP or sildenafil, but incubation with EDTA caused a time- and concentration-dependent shift to higher mobility (shift of Bands 2 and 3 to Band 1). Cyclic GMP 146-150 phosphodiesterase 5A Homo sapiens 14-18 21697861-0 2011 Expression and distribution of key enzymes of the cyclic GMP signaling in the human clitoris: relation to phosphodiesterase type 5 (PDE5). Cyclic GMP 50-60 phosphodiesterase 5A Homo sapiens 106-130 21697861-0 2011 Expression and distribution of key enzymes of the cyclic GMP signaling in the human clitoris: relation to phosphodiesterase type 5 (PDE5). Cyclic GMP 50-60 phosphodiesterase 5A Homo sapiens 132-136 21697861-4 2011 It has been suggested that human clitoral corpus cavernosum smooth muscle is regulated by nitric oxide (NO)/cyclic GMP and related key enzymes, such as NO synthases (NOSs) and the phosphodiesterase type 5 (PDE5). Cyclic GMP 108-118 phosphodiesterase 5A Homo sapiens 180-204 21697861-4 2011 It has been suggested that human clitoral corpus cavernosum smooth muscle is regulated by nitric oxide (NO)/cyclic GMP and related key enzymes, such as NO synthases (NOSs) and the phosphodiesterase type 5 (PDE5). Cyclic GMP 108-118 phosphodiesterase 5A Homo sapiens 206-210 21697861-5 2011 The present study evaluated in the human clitoris, by means of immunohistochemistry, the expression and distribution of key enzymes of the cyclic GMP pathway, such as the endothelial NOS, PDE2, PDE11 and cyclic GMP-dependent protein kinase type I (cGKI) in relation to the PDE5. Cyclic GMP 139-149 phosphodiesterase 5A Homo sapiens 273-277 21505183-4 2011 Here we show that SS can induce apoptosis of breast tumor cells, which predominantly rely on PDE5 for cGMP hydrolysis but not normal mammary epithelial cells, which rely on PDE isozymes other than PDE5 for cGMP hydrolysis. Cyclic GMP 102-106 phosphodiesterase 5A Homo sapiens 93-97 21525805-12 2011 PDE5 activity in RBCs regulates cGMP levels. Cyclic GMP 32-36 phosphodiesterase 5A Homo sapiens 0-4 21215707-0 2011 Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A. Cyclic GMP 68-72 phosphodiesterase 5A Homo sapiens 100-105 21193396-7 2011 Employing intramolecular bioluminescence resonance energy transfer, which can monitor conformational changes both in vitro and in intact cells, we show that binding of cGMP and sildenafil to PDE5 results in distinct conformations of the protein. Cyclic GMP 168-172 phosphodiesterase 5A Homo sapiens 191-195 21585174-7 2011 Among the other PDE5 inhibitors under development we report mirodenafil, lodenafil carbonate, avalafil and SLx-2101 It is likely that in the future molecules that act on pathways other than the one of NO/cGMP will be available. Cyclic GMP 204-208 phosphodiesterase 5A Homo sapiens 16-20 21251608-2 2011 describe that the oncogenic BRAF Val600Glu mutant, which occurs in about half of melanomas, downregulates the cGMP-hydrolysing phosphodiesterase PDE5A in melanoma cells through the ERK-MAPK cascade coupled to the POU-domain transcription factor BRN2, thereby increasing intracellular cGMP levels and promoting invasiveness. Cyclic GMP 110-114 phosphodiesterase 5A Homo sapiens 145-150 21251608-2 2011 describe that the oncogenic BRAF Val600Glu mutant, which occurs in about half of melanomas, downregulates the cGMP-hydrolysing phosphodiesterase PDE5A in melanoma cells through the ERK-MAPK cascade coupled to the POU-domain transcription factor BRN2, thereby increasing intracellular cGMP levels and promoting invasiveness. Cyclic GMP 284-288 phosphodiesterase 5A Homo sapiens 145-150 21215707-3 2011 This is because PDE5A downregulation leads to an increase in cGMP, which induces an increase in cytosolic Ca(2+), stimulating increased contractility and inducing invasion. Cyclic GMP 61-65 phosphodiesterase 5A Homo sapiens 16-21 20668100-9 2010 Sodium nitroprusside (10(-4) mol/l)-stimulated cGMP accumulation from inner medullary collecting duct cells was blunted in cells from pregnant vs. virgin or postpartum rats and was restored by treatment with the PDE5 inhibitor DMPPO (10(-7) mol/l). Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 212-216 21036891-2 2011 PDE5 inhibition, by blocking degradation of nitric oxide second-messenger cyclic guanosine monophosphate, might be beneficial. Cyclic GMP 74-104 phosphodiesterase 5A Homo sapiens 0-4 21695639-5 2011 Target related side effects may be bypassed by using PDE5 inhibitors with a different mode of action: PDE5, like PDE2, PDE6, PDE10, and PDE11, is a multidomain protein with an N-terminal tandem GAF domain, which in case of PDE5, is allosterically activated by cGMP. Cyclic GMP 260-264 phosphodiesterase 5A Homo sapiens 53-57 21695639-5 2011 Target related side effects may be bypassed by using PDE5 inhibitors with a different mode of action: PDE5, like PDE2, PDE6, PDE10, and PDE11, is a multidomain protein with an N-terminal tandem GAF domain, which in case of PDE5, is allosterically activated by cGMP. Cyclic GMP 260-264 phosphodiesterase 5A Homo sapiens 102-106 21695639-5 2011 Target related side effects may be bypassed by using PDE5 inhibitors with a different mode of action: PDE5, like PDE2, PDE6, PDE10, and PDE11, is a multidomain protein with an N-terminal tandem GAF domain, which in case of PDE5, is allosterically activated by cGMP. Cyclic GMP 260-264 phosphodiesterase 5A Homo sapiens 102-106 21695643-4 2011 Inhibitors of enzymes in the PDE5 family have been used to raise cGMP content in cardiac muscle in animal models of pressure overload, chronic beta-adrenergic receptor stimulation, ischemic injury, and doxorubicin toxicity, and have been shown to have antihypertrophic and cardioprotective actions. Cyclic GMP 65-69 phosphodiesterase 5A Homo sapiens 29-33 20958117-6 2011 Measured increases in cGMP levels by dipyridamole and NO was assessed by mathematical modeling and found to be consistent with inhibition of phosphodiesterase 5 (PDE5). Cyclic GMP 22-26 phosphodiesterase 5A Homo sapiens 141-160 20958117-6 2011 Measured increases in cGMP levels by dipyridamole and NO was assessed by mathematical modeling and found to be consistent with inhibition of phosphodiesterase 5 (PDE5). Cyclic GMP 22-26 phosphodiesterase 5A Homo sapiens 162-166 20958117-7 2011 The model could explain the unexpected efficiency of dipyridamole in inhibiting PDE5 at the measured cGMP levels, by the majority of cGMP being bound to cGMP-dependent protein kinase (PKG). Cyclic GMP 101-105 phosphodiesterase 5A Homo sapiens 80-84 20958117-7 2011 The model could explain the unexpected efficiency of dipyridamole in inhibiting PDE5 at the measured cGMP levels, by the majority of cGMP being bound to cGMP-dependent protein kinase (PKG). Cyclic GMP 133-137 phosphodiesterase 5A Homo sapiens 80-84 20861010-0 2010 Conformation changes, N-terminal involvement, and cGMP signal relay in the phosphodiesterase-5 GAF domain. Cyclic GMP 50-54 phosphodiesterase 5A Homo sapiens 75-94 20861010-1 2010 The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. Cyclic GMP 59-63 phosphodiesterase 5A Homo sapiens 16-35 20861010-1 2010 The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. Cyclic GMP 59-63 phosphodiesterase 5A Homo sapiens 37-41 20861010-1 2010 The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. Cyclic GMP 84-88 phosphodiesterase 5A Homo sapiens 16-35 20861010-1 2010 The activity of phosphodiesterase-5 (PDE5) is specific for cGMP and is regulated by cGMP binding to GAF-A in its regulatory domain. Cyclic GMP 84-88 phosphodiesterase 5A Homo sapiens 37-41 20698857-2 2010 The PDE2 and PDE5 families are allosterically activated by their substrate cGMP via regulatory so-called GAF domains. Cyclic GMP 75-79 phosphodiesterase 5A Homo sapiens 13-17 20698857-4 2010 EXPERIMENTAL APPROACH: Using fluorophore-tagged, isolated GAF domains of PDE2 and PDE5, promising cGMP analogues were selected. Cyclic GMP 98-102 phosphodiesterase 5A Homo sapiens 82-86 20698857-9 2010 CONCLUSIONS AND IMPLICATIONS: We conclude that the delayed activation of PDE5 is required to shape biphasic, spike-like cGMP signals. Cyclic GMP 120-124 phosphodiesterase 5A Homo sapiens 73-77 20698857-10 2010 Phosphorylation of PDE5 further enhances activity and conserves PDE5 activation, thereby enabling PDE5 to act as a molecular memory balancing cGMP responses to nitric oxide or natriuretic peptide signals. Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 19-23 20698857-10 2010 Phosphorylation of PDE5 further enhances activity and conserves PDE5 activation, thereby enabling PDE5 to act as a molecular memory balancing cGMP responses to nitric oxide or natriuretic peptide signals. Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 64-68 20698857-10 2010 Phosphorylation of PDE5 further enhances activity and conserves PDE5 activation, thereby enabling PDE5 to act as a molecular memory balancing cGMP responses to nitric oxide or natriuretic peptide signals. Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 64-68 20876730-5 2010 Consistent with its selectivity for inhibiting cGMP hydrolysis compared with cyclic AMP hydrolysis, SS inhibited the cGMP-specific PDE5 isozyme and increased cGMP levels in colon tumor cells. Cyclic GMP 117-121 phosphodiesterase 5A Homo sapiens 131-135 20876730-5 2010 Consistent with its selectivity for inhibiting cGMP hydrolysis compared with cyclic AMP hydrolysis, SS inhibited the cGMP-specific PDE5 isozyme and increased cGMP levels in colon tumor cells. Cyclic GMP 117-121 phosphodiesterase 5A Homo sapiens 131-135 21416994-6 2010 PDE5 inhibitors, by enhancing the vasodilator effect of cGMP, have been successfully applied to the treatment of erectile dysfunction. Cyclic GMP 56-60 phosphodiesterase 5A Homo sapiens 0-4 20695838-8 2010 We thus demonstrated that PDE5 inhibition acts on CXCR4 signalling in EPC and we can suppose an involvement of cGMP second messenger system in both EPC release from the bone marrow and EPC-mediated peripheral re-endothelization. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 26-30 20563733-1 2010 The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimental studies have shown that the nitric oxide/cGMP pathway plays an important role in the pathogenesis of glomerulonephritis, including IgA nephropathy (IgAN). Cyclic GMP 59-69 phosphodiesterase 5A Homo sapiens 4-23 20563733-1 2010 The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimental studies have shown that the nitric oxide/cGMP pathway plays an important role in the pathogenesis of glomerulonephritis, including IgA nephropathy (IgAN). Cyclic GMP 59-69 phosphodiesterase 5A Homo sapiens 25-30 20563733-1 2010 The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimental studies have shown that the nitric oxide/cGMP pathway plays an important role in the pathogenesis of glomerulonephritis, including IgA nephropathy (IgAN). Cyclic GMP 71-75 phosphodiesterase 5A Homo sapiens 4-23 20563733-1 2010 The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimental studies have shown that the nitric oxide/cGMP pathway plays an important role in the pathogenesis of glomerulonephritis, including IgA nephropathy (IgAN). Cyclic GMP 71-75 phosphodiesterase 5A Homo sapiens 25-30 20563733-1 2010 The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimental studies have shown that the nitric oxide/cGMP pathway plays an important role in the pathogenesis of glomerulonephritis, including IgA nephropathy (IgAN). Cyclic GMP 143-147 phosphodiesterase 5A Homo sapiens 4-23 20563733-1 2010 The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimental studies have shown that the nitric oxide/cGMP pathway plays an important role in the pathogenesis of glomerulonephritis, including IgA nephropathy (IgAN). Cyclic GMP 143-147 phosphodiesterase 5A Homo sapiens 25-30 19945540-1 2010 Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. Cyclic GMP 48-78 phosphodiesterase 5A Homo sapiens 114-119 19945540-1 2010 Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. Cyclic GMP 80-84 phosphodiesterase 5A Homo sapiens 114-119 20201788-6 2010 Phosphodiesterase (PDE)-5 inhibitors, produce an NO-dependent increase in intracellular cGMP concentration, have been a successful approach in the treatment of ED. Cyclic GMP 88-92 phosphodiesterase 5A Homo sapiens 0-25 20201788-9 2010 It is conceivable that sGC stimulators and/or activators may be more effective than PDE5 inhibitors in the treatment of ED in such circumstances by improving NO-sGC-cGMP signaling and erectile function. Cyclic GMP 165-169 phosphodiesterase 5A Homo sapiens 84-88 21537421-2 2010 They selectively inhibit intrapenile PDE5 isoenzyme which in turn increases intracellular cyclic guanosine monophosphate levels, thus resulting in prolonged relaxation of cavernosum smooth muscle cells and facilitating the erectile process. Cyclic GMP 90-120 phosphodiesterase 5A Homo sapiens 37-41 20206015-2 2010 The prepared analogues were evaluated for their capacity to inhibit the cyclic guanosine monophosphate (cGMP) selective phosphodiesterase 5 (PDE5) isozyme and the growth of human HT-29 colon adenocarcinoma cells. Cyclic GMP 72-102 phosphodiesterase 5A Homo sapiens 120-139 20206015-2 2010 The prepared analogues were evaluated for their capacity to inhibit the cyclic guanosine monophosphate (cGMP) selective phosphodiesterase 5 (PDE5) isozyme and the growth of human HT-29 colon adenocarcinoma cells. Cyclic GMP 72-102 phosphodiesterase 5A Homo sapiens 141-145 20206015-2 2010 The prepared analogues were evaluated for their capacity to inhibit the cyclic guanosine monophosphate (cGMP) selective phosphodiesterase 5 (PDE5) isozyme and the growth of human HT-29 colon adenocarcinoma cells. Cyclic GMP 104-108 phosphodiesterase 5A Homo sapiens 120-139 20206015-2 2010 The prepared analogues were evaluated for their capacity to inhibit the cyclic guanosine monophosphate (cGMP) selective phosphodiesterase 5 (PDE5) isozyme and the growth of human HT-29 colon adenocarcinoma cells. Cyclic GMP 104-108 phosphodiesterase 5A Homo sapiens 141-145 20086037-1 2010 cGMP-specific phosphodiesterase (PDE5) has become a target for drug development for the treatment of a number of physiological dysfunctions, affected by changes in the cGMP/cGMP-dependent protein kinase (PKG) signaling pathway. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 33-37 20086037-3 2010 We showed previously that PDE5 could be converted from a low-activity (nonactivated) state to a high-activity state upon cGMP binding to the GAF-A domain with higher sensitivities toward sildenafil (EMBO J 22:469-478, 2003). Cyclic GMP 121-125 phosphodiesterase 5A Homo sapiens 26-30 20086037-8 2010 In human platelet, higher sensitivity of PDE5 for sildenafil inhibition has been detected after blocking cGMP-binding sites of the GAF-A domain. Cyclic GMP 105-109 phosphodiesterase 5A Homo sapiens 41-45 20086037-9 2010 Thus, our data demonstrate that high sensitivity of PDE5 for sildenafil can be obtained not only through cGMP-induced activation of PDE, but also through cGMP-independent modulation of PDE5 in the nonactivated state, possibly through protein-protein interaction. Cyclic GMP 105-109 phosphodiesterase 5A Homo sapiens 52-56 20086037-9 2010 Thus, our data demonstrate that high sensitivity of PDE5 for sildenafil can be obtained not only through cGMP-induced activation of PDE, but also through cGMP-independent modulation of PDE5 in the nonactivated state, possibly through protein-protein interaction. Cyclic GMP 154-158 phosphodiesterase 5A Homo sapiens 52-56 20491634-1 2010 PDE5 belongs to a superfamily of enzymes that catalyzes the hydrolysis of cyclic nucleotides cAMP and cGMP to the corresponding 5-nucleoside monophosphate. Cyclic GMP 102-106 phosphodiesterase 5A Homo sapiens 0-4 19887943-2 2010 Phosphodiesterase-5 (PDE5) inhibitors increase intracellular concentrations of cyclic guanosine monophosphate. Cyclic GMP 79-109 phosphodiesterase 5A Homo sapiens 0-19 19887943-2 2010 Phosphodiesterase-5 (PDE5) inhibitors increase intracellular concentrations of cyclic guanosine monophosphate. Cyclic GMP 79-109 phosphodiesterase 5A Homo sapiens 21-25 19781847-3 2009 OBJECTIVE: To evaluate if platelet cyclic guanosine monophosphate (cGMP) could represent a valuable marker for PDE5-I activity in ED. Cyclic GMP 35-65 phosphodiesterase 5A Homo sapiens 111-115 19796053-2 2010 PDE5 is highly expressed in rat and human bladder, where it regulates cyclic guanosine monophosphate (cGMP) degradation, muscle tone, and proliferation. Cyclic GMP 70-100 phosphodiesterase 5A Homo sapiens 0-4 19796053-2 2010 PDE5 is highly expressed in rat and human bladder, where it regulates cyclic guanosine monophosphate (cGMP) degradation, muscle tone, and proliferation. Cyclic GMP 102-106 phosphodiesterase 5A Homo sapiens 0-4 19796053-6 2010 Proliferation assay was used as readout of PDE5 activity, evaluated as ability of vardenafil to increase the antiproliferative effect of different nitric oxide (NO)/cGMP pathway activators [the PDE5-resistant cGMP analog Sp-8-Br-PET-cGMPS, the NO donor sodium nitroprusside (SNP), and the soluble guanylate cyclase (sGC) stimulator BAY 41-8543]. Cyclic GMP 209-213 phosphodiesterase 5A Homo sapiens 194-198 19796053-6 2010 Proliferation assay was used as readout of PDE5 activity, evaluated as ability of vardenafil to increase the antiproliferative effect of different nitric oxide (NO)/cGMP pathway activators [the PDE5-resistant cGMP analog Sp-8-Br-PET-cGMPS, the NO donor sodium nitroprusside (SNP), and the soluble guanylate cyclase (sGC) stimulator BAY 41-8543]. Cyclic GMP 233-238 phosphodiesterase 5A Homo sapiens 194-198 19665054-1 2009 Native phosphodiesterase-5 (PDE5) homodimer contains distinct non-catalytic cGMP allosteric sites and catalytic sites for cGMP hydrolysis. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 7-26 19665054-1 2009 Native phosphodiesterase-5 (PDE5) homodimer contains distinct non-catalytic cGMP allosteric sites and catalytic sites for cGMP hydrolysis. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 28-32 19665054-1 2009 Native phosphodiesterase-5 (PDE5) homodimer contains distinct non-catalytic cGMP allosteric sites and catalytic sites for cGMP hydrolysis. Cyclic GMP 122-126 phosphodiesterase 5A Homo sapiens 7-26 19665054-1 2009 Native phosphodiesterase-5 (PDE5) homodimer contains distinct non-catalytic cGMP allosteric sites and catalytic sites for cGMP hydrolysis. Cyclic GMP 122-126 phosphodiesterase 5A Homo sapiens 28-32 19665054-2 2009 Purified recombinant PDE5 was activated by pre-incubation with cGMP. Cyclic GMP 63-67 phosphodiesterase 5A Homo sapiens 21-25 19665054-3 2009 Relatively low concentrations of cGMP produced a Native PAGE gel shift of PDE5 from a single band position (lower band) to a band with decreased mobility (upper band); higher concentrations of cGMP produced a band of intermediate mobility (middle band) in addition to the upper band. Cyclic GMP 33-37 phosphodiesterase 5A Homo sapiens 74-78 19665054-4 2009 Two point mutations (G659A and G659P) near the catalytic site that reduced affinity for cGMP substrate retained allosteric cGMP-binding affinity like that of WT PDE5 but displayed cGMP-induced gel shift only to the middle-band position. Cyclic GMP 88-92 phosphodiesterase 5A Homo sapiens 161-165 19665054-4 2009 Two point mutations (G659A and G659P) near the catalytic site that reduced affinity for cGMP substrate retained allosteric cGMP-binding affinity like that of WT PDE5 but displayed cGMP-induced gel shift only to the middle-band position. Cyclic GMP 123-127 phosphodiesterase 5A Homo sapiens 161-165 19665054-4 2009 Two point mutations (G659A and G659P) near the catalytic site that reduced affinity for cGMP substrate retained allosteric cGMP-binding affinity like that of WT PDE5 but displayed cGMP-induced gel shift only to the middle-band position. Cyclic GMP 123-127 phosphodiesterase 5A Homo sapiens 161-165 19665054-6 2009 Millimolar cGMP was required for gel shift of PDE5 when added to the pre-incubation before Native PAGE, presumably due to removal of most of the cGMP during electrophoresis, but micromolar cGMP was sufficient for this effect if cGMP was included in the native gel buffer. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 46-50 19665054-6 2009 Millimolar cGMP was required for gel shift of PDE5 when added to the pre-incubation before Native PAGE, presumably due to removal of most of the cGMP during electrophoresis, but micromolar cGMP was sufficient for this effect if cGMP was included in the native gel buffer. Cyclic GMP 145-149 phosphodiesterase 5A Homo sapiens 46-50 19665054-6 2009 Millimolar cGMP was required for gel shift of PDE5 when added to the pre-incubation before Native PAGE, presumably due to removal of most of the cGMP during electrophoresis, but micromolar cGMP was sufficient for this effect if cGMP was included in the native gel buffer. Cyclic GMP 145-149 phosphodiesterase 5A Homo sapiens 46-50 19665054-6 2009 Millimolar cGMP was required for gel shift of PDE5 when added to the pre-incubation before Native PAGE, presumably due to removal of most of the cGMP during electrophoresis, but micromolar cGMP was sufficient for this effect if cGMP was included in the native gel buffer. Cyclic GMP 145-149 phosphodiesterase 5A Homo sapiens 46-50 19665054-7 2009 cGMP-induced gel shift was associated with stimulation of PDE5 catalytic activity, and the rates of onset and reversibility of this effect suggested that it was due to cGMP binding to the allosteric site. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 58-62 19665054-7 2009 cGMP-induced gel shift was associated with stimulation of PDE5 catalytic activity, and the rates of onset and reversibility of this effect suggested that it was due to cGMP binding to the allosteric site. Cyclic GMP 168-172 phosphodiesterase 5A Homo sapiens 58-62 19665054-10 2009 PDE5 activation or gel shift was reversed by lowering cGMP with dilution followed by at least 1h of incubation. Cyclic GMP 54-58 phosphodiesterase 5A Homo sapiens 0-4 19665054-11 2009 Such slow reversibility could prolong effects of cGMP on PDE5 in cells after decline of this nucleotide. Cyclic GMP 49-53 phosphodiesterase 5A Homo sapiens 57-61 19665054-14 2009 Thus, kinetic effect of binding of a high-affinity PDE5 inhibitor to the catalytic site is more readily reversible than that obtained by cGMP binding to the allosteric site. Cyclic GMP 137-141 phosphodiesterase 5A Homo sapiens 51-55 19665054-15 2009 It is concluded that cGMP or PDE5 inhibitor binding to the catalytic site, or ligand binding to both the catalytic site and allosteric site simultaneously, changes PDE5 to a similar physical form; this form is distinct from that produced by cGMP binding to the allosteric site, which activates the enzyme and reverses more slowly. Cyclic GMP 21-25 phosphodiesterase 5A Homo sapiens 164-168 19665054-15 2009 It is concluded that cGMP or PDE5 inhibitor binding to the catalytic site, or ligand binding to both the catalytic site and allosteric site simultaneously, changes PDE5 to a similar physical form; this form is distinct from that produced by cGMP binding to the allosteric site, which activates the enzyme and reverses more slowly. Cyclic GMP 241-245 phosphodiesterase 5A Homo sapiens 29-33 19665054-15 2009 It is concluded that cGMP or PDE5 inhibitor binding to the catalytic site, or ligand binding to both the catalytic site and allosteric site simultaneously, changes PDE5 to a similar physical form; this form is distinct from that produced by cGMP binding to the allosteric site, which activates the enzyme and reverses more slowly. Cyclic GMP 241-245 phosphodiesterase 5A Homo sapiens 164-168 19608425-2 2009 Its mechanism of action is based on the selective inhibition of phosphodiesterase-5 (PDE5), specific to guanosine 3",5"-cyclic monophosphate (cGMP). Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 85-89 19096931-5 2009 More recently, inhibitors of PDE5 cyclic nucleotide phosphodiesterases have been used as cGMP-raising agents in vascular smooth muscle. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 29-33 19608425-2 2009 Its mechanism of action is based on the selective inhibition of phosphodiesterase-5 (PDE5), specific to guanosine 3",5"-cyclic monophosphate (cGMP). Cyclic GMP 104-140 phosphodiesterase 5A Homo sapiens 64-83 19608425-2 2009 Its mechanism of action is based on the selective inhibition of phosphodiesterase-5 (PDE5), specific to guanosine 3",5"-cyclic monophosphate (cGMP). Cyclic GMP 104-140 phosphodiesterase 5A Homo sapiens 85-89 19608425-2 2009 Its mechanism of action is based on the selective inhibition of phosphodiesterase-5 (PDE5), specific to guanosine 3",5"-cyclic monophosphate (cGMP). Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 64-83 19781847-3 2009 OBJECTIVE: To evaluate if platelet cyclic guanosine monophosphate (cGMP) could represent a valuable marker for PDE5-I activity in ED. Cyclic GMP 67-71 phosphodiesterase 5A Homo sapiens 111-115 19781847-14 2009 CONCLUSIONS: Platelet cGMP could represent a relatively simple, reliable, and objective biomarker of PDE5-I activity in ED clinical studies. Cyclic GMP 22-26 phosphodiesterase 5A Homo sapiens 101-105 20101899-2 2009 Phosphodiesterase-5 (PDE5) is mainly involved in the smooth muscle cell cGMP inactivation. Cyclic GMP 72-76 phosphodiesterase 5A Homo sapiens 0-19 20101899-2 2009 Phosphodiesterase-5 (PDE5) is mainly involved in the smooth muscle cell cGMP inactivation. Cyclic GMP 72-76 phosphodiesterase 5A Homo sapiens 21-25 20101899-3 2009 Chemical inhibition of PDE5 has recently become a valid therapeutic option of nitric oxide pathway potentiation via cell cGMP availability. Cyclic GMP 121-125 phosphodiesterase 5A Homo sapiens 23-27 19660688-12 2009 This study provides in vivo evidence that phosphodiesterase 5A inhibition restores sensitivity of pulmonary vasculature to endogenous cGMP-dependent vasodilators. Cyclic GMP 134-138 phosphodiesterase 5A Homo sapiens 42-62 19768639-4 2009 Phosphodiesterase type 5 (PDE-5) is implicated in this process by inactivating cyclic guanosine monophosphate, the nitric oxide pathway second messenger. Cyclic GMP 79-109 phosphodiesterase 5A Homo sapiens 0-24 19768639-4 2009 Phosphodiesterase type 5 (PDE-5) is implicated in this process by inactivating cyclic guanosine monophosphate, the nitric oxide pathway second messenger. Cyclic GMP 79-109 phosphodiesterase 5A Homo sapiens 26-31 19689430-3 2009 For PDE2A, PDE5A and PDE6 the GAF domains have been shown to bind cGMP with high affinity. Cyclic GMP 66-70 phosphodiesterase 5A Homo sapiens 11-16 19852267-1 2009 OBJECTIVE: To investigate the effect of phosphodiesterase type 5 (PDE5) small interfering RNA (siRNA) on cyclic guanosine monophosphatethe (cGMP) in the smooth muscle cells of human corpus cavernosum, and to provide laboratory evidence for the application of the RNA interference (RNAi) technique for the treatment of erectile dysfunction. Cyclic GMP 140-144 phosphodiesterase 5A Homo sapiens 40-64 19239452-7 2009 PDE5-Is can inhibit human stromal cell proliferation of the prostate mediated by cGMP accumulation. Cyclic GMP 81-85 phosphodiesterase 5A Homo sapiens 0-4 19852267-1 2009 OBJECTIVE: To investigate the effect of phosphodiesterase type 5 (PDE5) small interfering RNA (siRNA) on cyclic guanosine monophosphatethe (cGMP) in the smooth muscle cells of human corpus cavernosum, and to provide laboratory evidence for the application of the RNA interference (RNAi) technique for the treatment of erectile dysfunction. Cyclic GMP 140-144 phosphodiesterase 5A Homo sapiens 66-70 19852267-6 2009 CONCLUSION: The rAd5-shRNA-PDE5A3 can obviously increase the cGMP level in the smooth muscle cells of human corpus cavernosum, and enhance the inhibition of the PDE5 gene. Cyclic GMP 61-65 phosphodiesterase 5A Homo sapiens 27-31 19428813-7 2009 Treatment of rats with chronic HE or hyperammonemia with inhibitors of phosphodiesterase 5 restores the function of the glutamate-nitric oxide-cGMP pathway and cGMP levels in brain as well as the ability to learn a Y maze conditional discrimination task. Cyclic GMP 143-147 phosphodiesterase 5A Homo sapiens 71-90 19428813-7 2009 Treatment of rats with chronic HE or hyperammonemia with inhibitors of phosphodiesterase 5 restores the function of the glutamate-nitric oxide-cGMP pathway and cGMP levels in brain as well as the ability to learn a Y maze conditional discrimination task. Cyclic GMP 160-164 phosphodiesterase 5A Homo sapiens 71-90 19428813-10 2009 Increasing cGMP by using inhibitors of phosphodiesterase 5 (PDE-5) or anti-inflammatories (under safe conditions) would be therefore a new therapeutic approach to improve learning and memory performance in individuals with minimal or clinical HE. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 39-58 19428813-10 2009 Increasing cGMP by using inhibitors of phosphodiesterase 5 (PDE-5) or anti-inflammatories (under safe conditions) would be therefore a new therapeutic approach to improve learning and memory performance in individuals with minimal or clinical HE. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 60-65 19352616-10 2009 CONCLUSION: Despite the fact that inhibitors of PDE1, PDE4, and PDE5 exerted only a weak relaxant response on detrusor strips precontracted by carbachol, our findings indicate that both the cAMP and cGMP pathways might be involved in the relaxation mechanism of human detrusor smooth muscle. Cyclic GMP 199-203 phosphodiesterase 5A Homo sapiens 64-68 19562633-2 2009 PDE5 inhibitors supply penile erection by inhibiting the hydrolysis of cGMP and therefore relaxing the corpus cavernosum. Cyclic GMP 71-75 phosphodiesterase 5A Homo sapiens 0-4 19638092-1 2009 BACKGROUND AND AIM: Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. Cyclic GMP 68-98 phosphodiesterase 5A Homo sapiens 134-139 19638092-1 2009 BACKGROUND AND AIM: Sildenafil, a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase (PDE)5, has a relaxant effect on the smooth muscle cells of the arterioles supplying the human corpus cavernosum acting via nitric oxide (NO)-dependent mechanism. Cyclic GMP 100-104 phosphodiesterase 5A Homo sapiens 134-139 19243765-2 2009 Vardenafil inhibits the activity of phosphodiesterase type 5 (PDE-5), which degrades cyclic guanossine monophosphate (cGMP) and results in relaxation of smooth muscle. Cyclic GMP 118-122 phosphodiesterase 5A Homo sapiens 36-60 19243765-2 2009 Vardenafil inhibits the activity of phosphodiesterase type 5 (PDE-5), which degrades cyclic guanossine monophosphate (cGMP) and results in relaxation of smooth muscle. Cyclic GMP 118-122 phosphodiesterase 5A Homo sapiens 62-67 19267844-12 2009 At the gene level, PDE5 expression is regulated at two alternative promoters, PDE5A and PDE5A2, both of which are positively regulated by cyclic adenosine monophosphate and cGMP. Cyclic GMP 173-177 phosphodiesterase 5A Homo sapiens 19-23 19377497-1 2009 Phosphodiesterase 5 (PDE5) selectively hydrolyzes cyclic guanosine monophosphate. Cyclic GMP 50-80 phosphodiesterase 5A Homo sapiens 0-19 19377497-1 2009 Phosphodiesterase 5 (PDE5) selectively hydrolyzes cyclic guanosine monophosphate. Cyclic GMP 50-80 phosphodiesterase 5A Homo sapiens 21-25 19416631-1 2009 cGMP-specific phosphodiesterase 5 (PDE5) inhibition has been shown to be effective in improving pulmonary haemodynamics in both animal models and clinic patients with pulmonary hypertension. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 35-39 19416631-8 2009 Meanwhile, these two pathways are also separately modulated by enhanced cGMP-PKG signalling derived from inhibition of PDE5 with sildenafil to confer the overall roles of sildenafil against pulmonary hypertension. Cyclic GMP 72-76 phosphodiesterase 5A Homo sapiens 119-123 19267844-1 2009 INTRODUCTION: Penile detumescence depends on the hydrolysis of cyclic guanosine monophosphate (cGMP) by phosphodiesterase type 5 (PDE5). Cyclic GMP 63-93 phosphodiesterase 5A Homo sapiens 104-128 19267844-1 2009 INTRODUCTION: Penile detumescence depends on the hydrolysis of cyclic guanosine monophosphate (cGMP) by phosphodiesterase type 5 (PDE5). Cyclic GMP 63-93 phosphodiesterase 5A Homo sapiens 130-134 19267844-1 2009 INTRODUCTION: Penile detumescence depends on the hydrolysis of cyclic guanosine monophosphate (cGMP) by phosphodiesterase type 5 (PDE5). Cyclic GMP 95-99 phosphodiesterase 5A Homo sapiens 104-128 19267844-1 2009 INTRODUCTION: Penile detumescence depends on the hydrolysis of cyclic guanosine monophosphate (cGMP) by phosphodiesterase type 5 (PDE5). Cyclic GMP 95-99 phosphodiesterase 5A Homo sapiens 130-134 19267844-9 2009 At protein level, PDE5 is activated by phosphorylation and/or allosteric cGMP binding. Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 18-22 19267844-12 2009 At the gene level, PDE5 expression is regulated at two alternative promoters, PDE5A and PDE5A2, both of which are positively regulated by cyclic adenosine monophosphate and cGMP. Cyclic GMP 173-177 phosphodiesterase 5A Homo sapiens 78-83 19028977-1 2009 Type 5 phosphodiesterase (PDE5) inhibitors increase endothelial cell cGMP and promote angiogenesis. Cyclic GMP 69-73 phosphodiesterase 5A Homo sapiens 26-30 19139381-1 2009 BACKGROUND: Ventricular expression of phosphodiesterase-5 (PDE5), an enzyme responsible for cGMP catabolism, is increased in human right ventricular hypertrophy, but its role in left ventricular (LV) failure remains incompletely understood. Cyclic GMP 92-96 phosphodiesterase 5A Homo sapiens 59-63 19060915-3 2009 The PDE type-3, -4, and -5 (PDE3, PDE4, PDE5) are localized to specific regions of the cardiomyocyte, such as the sarcoplasmic reticulum and Z-disc, where they are likely to influence cAMP/cGMP signaling to the end effectors of contractility. Cyclic GMP 189-193 phosphodiesterase 5A Homo sapiens 40-44 18938025-0 2009 Mechanism of action of PDE5 inhibitors in LUTS and ED: the NO-cGMP pathway. Cyclic GMP 62-66 phosphodiesterase 5A Homo sapiens 23-27 19089343-2 2009 Thus cGMP is a key second messenger and targeting this pathway by increasing intracellular cGMP levels is a very successful approach in pharmacology as shown for nitrates, PDE5 inhibitors and more recently for stimulators of the guanylate cyclase. Cyclic GMP 5-9 phosphodiesterase 5A Homo sapiens 172-176 19089343-2 2009 Thus cGMP is a key second messenger and targeting this pathway by increasing intracellular cGMP levels is a very successful approach in pharmacology as shown for nitrates, PDE5 inhibitors and more recently for stimulators of the guanylate cyclase. Cyclic GMP 91-95 phosphodiesterase 5A Homo sapiens 172-176 19089343-3 2009 Besides the beneficial effects of cGMP elevation in cardiac, vascular, pulmonary, renal or liver disorders the launch of PDE5 inhibitors for the treatment of erectile dysfunction 10 years ago, has directed a lot of attention to the NO/cGMP signaling in the lower urinary tract. Cyclic GMP 235-239 phosphodiesterase 5A Homo sapiens 121-125 19089343-4 2009 Triggered by the use of PDE5 inhibitors in ED it turned out that cGMP is a common regulatory mechanism for lower urinary tract function also beyond ED. Cyclic GMP 65-69 phosphodiesterase 5A Homo sapiens 24-28 19089344-3 2009 In platelets, cGMP synthesis is catalyzed by sGC, whereas PDE2, PDE3 and PDE5 are responsible for cGMP degradation. Cyclic GMP 98-102 phosphodiesterase 5A Homo sapiens 73-77 18790048-1 2008 Cyclic GMP-selective phosphodiesterase type 5 (PDE5) has been traditionally thought to play a little role in cardiac myocytes, yet recent studies using selective inhibitors such as sildenafil suggest it can potently modulate acute and chronic cardiac stress responses. Cyclic GMP 0-10 phosphodiesterase 5A Homo sapiens 47-51 18716761-1 2009 BACKGROUND: Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine monophosphate (cGMP) concentrations in the intracellular pathway activated by N-methyl-D-aspartic acid receptors which is believed to mediate long-term potentiation and memory consolidation. Cyclic GMP 59-89 phosphodiesterase 5A Homo sapiens 12-31 18716761-1 2009 BACKGROUND: Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine monophosphate (cGMP) concentrations in the intracellular pathway activated by N-methyl-D-aspartic acid receptors which is believed to mediate long-term potentiation and memory consolidation. Cyclic GMP 59-89 phosphodiesterase 5A Homo sapiens 33-37 18716761-1 2009 BACKGROUND: Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine monophosphate (cGMP) concentrations in the intracellular pathway activated by N-methyl-D-aspartic acid receptors which is believed to mediate long-term potentiation and memory consolidation. Cyclic GMP 91-95 phosphodiesterase 5A Homo sapiens 12-31 18716761-1 2009 BACKGROUND: Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine monophosphate (cGMP) concentrations in the intracellular pathway activated by N-methyl-D-aspartic acid receptors which is believed to mediate long-term potentiation and memory consolidation. Cyclic GMP 91-95 phosphodiesterase 5A Homo sapiens 33-37 18607596-4 2008 The hypothesis that an impaired NO/cGMP-signaling may contribute to the pathophysiology of benign prostatic hyperplasia (BPH) is supported by the results from randomized, placebo-controlled clinical studies, indicating that NO donor drugs and PDE5-inhibitors sildenafil, tadalafil and vardenafil may be useful to treat storage and voiding dysfunctions resulting from LUTS in men. Cyclic GMP 35-39 phosphodiesterase 5A Homo sapiens 243-247 18631254-2 2008 The inhibition of phosphodiesterase-5 (PDE-5), an enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP), is widely used in the treatment of erectile dysfunction. Cyclic GMP 92-122 phosphodiesterase 5A Homo sapiens 18-37 18631254-2 2008 The inhibition of phosphodiesterase-5 (PDE-5), an enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP), is widely used in the treatment of erectile dysfunction. Cyclic GMP 92-122 phosphodiesterase 5A Homo sapiens 39-44 18631254-2 2008 The inhibition of phosphodiesterase-5 (PDE-5), an enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP), is widely used in the treatment of erectile dysfunction. Cyclic GMP 124-128 phosphodiesterase 5A Homo sapiens 18-37 18631254-2 2008 The inhibition of phosphodiesterase-5 (PDE-5), an enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP), is widely used in the treatment of erectile dysfunction. Cyclic GMP 124-128 phosphodiesterase 5A Homo sapiens 39-44 18689467-9 2008 CONCLUSIONS: These data demonstrate that PDE5 is a key regulator of cGMP-mediated vasodilation by ANP in the pulmonary, but not systemic, vasculature, thereby explaining the pulmonary selectivity of PDE5 inhibitors. Cyclic GMP 68-72 phosphodiesterase 5A Homo sapiens 41-45 18660830-9 2008 As PDE5 hydrolyses cyclic GMP, this effect may blunt the vasculoprotective actions of NO. Cyclic GMP 19-29 phosphodiesterase 5A Homo sapiens 3-7 18596704-3 2008 cGMP-specific PDE5 is one of the PDEs that have been intensively studied because of its fundamental pharmacological relevance, as oral PDE5 inhibitors are used successfully in treating erectile dysfunction. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 14-18 18596704-3 2008 cGMP-specific PDE5 is one of the PDEs that have been intensively studied because of its fundamental pharmacological relevance, as oral PDE5 inhibitors are used successfully in treating erectile dysfunction. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 135-139 18761597-1 2008 INTRODUCTION: Phosphodiesterase type 5 (PDE5) hydrolyses cyclic guanylate monophosphate (cGMP) specifically to 5" GMP. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 14-38 18761597-1 2008 INTRODUCTION: Phosphodiesterase type 5 (PDE5) hydrolyses cyclic guanylate monophosphate (cGMP) specifically to 5" GMP. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 40-44 18689467-9 2008 CONCLUSIONS: These data demonstrate that PDE5 is a key regulator of cGMP-mediated vasodilation by ANP in the pulmonary, but not systemic, vasculature, thereby explaining the pulmonary selectivity of PDE5 inhibitors. Cyclic GMP 68-72 phosphodiesterase 5A Homo sapiens 199-203 18757735-0 2008 Compartmentation and compartment-specific regulation of PDE5 by protein kinase G allows selective cGMP-mediated regulation of platelet functions. Cyclic GMP 98-102 phosphodiesterase 5A Homo sapiens 56-60 18635550-7 2008 Second, we generated a GAF tandem chimera that consisted of the cGMP-binding GAF-A unit from hPDE5A1, which signals through cGMP in PDE5, and the GAF-B from hPDE10A1, which signals through cAMP in PDE10. Cyclic GMP 64-68 phosphodiesterase 5A Homo sapiens 94-98 18635550-7 2008 Second, we generated a GAF tandem chimera that consisted of the cGMP-binding GAF-A unit from hPDE5A1, which signals through cGMP in PDE5, and the GAF-B from hPDE10A1, which signals through cAMP in PDE10. Cyclic GMP 124-128 phosphodiesterase 5A Homo sapiens 94-98 18757735-4 2008 Our data identify PDE5 as an integral component of a protein kinase G1beta (PKG1beta)-containing signaling complex, reported previously to coordinate cGMP-mediated inhibition of inositol-1, 4, 5-trisphosphate receptor type 1 (IP(3)R1)-mediated Ca(2+)-release. Cyclic GMP 150-154 phosphodiesterase 5A Homo sapiens 18-22 18757735-7 2008 Based on these findings, we elaborate a model in which PKG selectively activates PDE5 within a defined microdomain in platelets and propose that this mechanism allows spatial and temporal regulation of cGMP signaling in these cells. Cyclic GMP 202-206 phosphodiesterase 5A Homo sapiens 81-85 18593576-2 2008 Phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, prolong the NO effects by inhibiting cGMP breakdown. Cyclic GMP 96-100 phosphodiesterase 5A Homo sapiens 0-19 18593576-2 2008 Phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, prolong the NO effects by inhibiting cGMP breakdown. Cyclic GMP 96-100 phosphodiesterase 5A Homo sapiens 21-25 18534985-0 2008 Solution structure of the cGMP binding GAF domain from phosphodiesterase 5: insights into nucleotide specificity, dimerization, and cGMP-dependent conformational change. Cyclic GMP 26-30 phosphodiesterase 5A Homo sapiens 55-74 18534985-0 2008 Solution structure of the cGMP binding GAF domain from phosphodiesterase 5: insights into nucleotide specificity, dimerization, and cGMP-dependent conformational change. Cyclic GMP 132-136 phosphodiesterase 5A Homo sapiens 55-74 18534985-1 2008 Phosphodiesterase 5 (PDE5) controls intracellular levels of cGMP through its regulation of cGMP hydrolysis. Cyclic GMP 60-64 phosphodiesterase 5A Homo sapiens 0-19 18534985-1 2008 Phosphodiesterase 5 (PDE5) controls intracellular levels of cGMP through its regulation of cGMP hydrolysis. Cyclic GMP 60-64 phosphodiesterase 5A Homo sapiens 21-25 18534985-1 2008 Phosphodiesterase 5 (PDE5) controls intracellular levels of cGMP through its regulation of cGMP hydrolysis. Cyclic GMP 91-95 phosphodiesterase 5A Homo sapiens 0-19 18534985-1 2008 Phosphodiesterase 5 (PDE5) controls intracellular levels of cGMP through its regulation of cGMP hydrolysis. Cyclic GMP 91-95 phosphodiesterase 5A Homo sapiens 21-25 18534985-3 2008 We present the NMR solution structure of the cGMP-bound PDE5A GAF A domain. Cyclic GMP 45-49 phosphodiesterase 5A Homo sapiens 56-61 18418391-2 2008 Phosphodiesterase-5 (PDE5) in VSMC breaks down cGMP to counter this effect. Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 0-19 18553893-5 2008 Chamomile inhibited cAMP-PDE activity (IC50 = 17.9-40.5 microg/mL), while cGMP-PDE5 was less affected (-15% at 50 microg/mL). Cyclic GMP 74-78 phosphodiesterase 5A Homo sapiens 79-83 18591337-4 2008 In the search for therapeutic strategies that engage the cGMP signalling pathway for the treatment of pulmonary arterial hypertension (PAH), inhibition of cGMP metabolism by phosphodiesterase type 5 (PDE5)-targeted compounds has proven most successful to date. Cyclic GMP 57-61 phosphodiesterase 5A Homo sapiens 174-198 18591337-4 2008 In the search for therapeutic strategies that engage the cGMP signalling pathway for the treatment of pulmonary arterial hypertension (PAH), inhibition of cGMP metabolism by phosphodiesterase type 5 (PDE5)-targeted compounds has proven most successful to date. Cyclic GMP 57-61 phosphodiesterase 5A Homo sapiens 200-204 18591337-4 2008 In the search for therapeutic strategies that engage the cGMP signalling pathway for the treatment of pulmonary arterial hypertension (PAH), inhibition of cGMP metabolism by phosphodiesterase type 5 (PDE5)-targeted compounds has proven most successful to date. Cyclic GMP 155-159 phosphodiesterase 5A Homo sapiens 174-198 18591337-4 2008 In the search for therapeutic strategies that engage the cGMP signalling pathway for the treatment of pulmonary arterial hypertension (PAH), inhibition of cGMP metabolism by phosphodiesterase type 5 (PDE5)-targeted compounds has proven most successful to date. Cyclic GMP 155-159 phosphodiesterase 5A Homo sapiens 200-204 18418391-2 2008 Phosphodiesterase-5 (PDE5) in VSMC breaks down cGMP to counter this effect. Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 21-25 18331270-3 2008 L-arginine (L-arg), the precursor of NO, and selective phosphodiesterase type 5 (PDE-5) inhibitors that increase levels of intracellular cGMP may complementarily enhance VEGF synthesis in corpus cavernosal smooth muscle cells (CCSMCs), and may consequently restore impaired endothelial function. Cyclic GMP 137-141 phosphodiesterase 5A Homo sapiens 55-79 18331270-3 2008 L-arginine (L-arg), the precursor of NO, and selective phosphodiesterase type 5 (PDE-5) inhibitors that increase levels of intracellular cGMP may complementarily enhance VEGF synthesis in corpus cavernosal smooth muscle cells (CCSMCs), and may consequently restore impaired endothelial function. Cyclic GMP 137-141 phosphodiesterase 5A Homo sapiens 81-86 18501878-7 2008 cGMP levels in the cultured forebrain neurons were also increased when cells were stimulated with DEANO in the presence of the selective PDE inhibitors BAY 60-7550 (PDE2), sildenafil (PDE5), or the mixed type inhibitor papaverine (PDE2,5,10). Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 184-188 18614424-4 2008 Tadalafil (Cialis) is also a PDE5 inhibitor that increases the level of cyclic guanosine monophosphate (cGMP) in cavernous smooth muscle cells. Cyclic GMP 72-102 phosphodiesterase 5A Homo sapiens 29-33 18614424-4 2008 Tadalafil (Cialis) is also a PDE5 inhibitor that increases the level of cyclic guanosine monophosphate (cGMP) in cavernous smooth muscle cells. Cyclic GMP 104-108 phosphodiesterase 5A Homo sapiens 29-33 18293931-0 2008 The GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5) is a sensor and a sink for cGMP. Cyclic GMP 22-26 phosphodiesterase 5A Homo sapiens 69-73 18765082-3 2008 Inhibition of phosphodiesterase-5 (PDE5) is a new therapeutic strategy for overexpressing nitric oxide signaling by increasing the availability of cyclic guanosine monophosphate (cGMP). Cyclic GMP 147-177 phosphodiesterase 5A Homo sapiens 14-33 18765082-3 2008 Inhibition of phosphodiesterase-5 (PDE5) is a new therapeutic strategy for overexpressing nitric oxide signaling by increasing the availability of cyclic guanosine monophosphate (cGMP). Cyclic GMP 147-177 phosphodiesterase 5A Homo sapiens 35-39 18765082-3 2008 Inhibition of phosphodiesterase-5 (PDE5) is a new therapeutic strategy for overexpressing nitric oxide signaling by increasing the availability of cyclic guanosine monophosphate (cGMP). Cyclic GMP 179-183 phosphodiesterase 5A Homo sapiens 14-33 18765082-3 2008 Inhibition of phosphodiesterase-5 (PDE5) is a new therapeutic strategy for overexpressing nitric oxide signaling by increasing the availability of cyclic guanosine monophosphate (cGMP). Cyclic GMP 179-183 phosphodiesterase 5A Homo sapiens 35-39 18765082-6 2008 Basic studies suggest that increased cGMP activity by PDE5 inhibition has potentially favorable direct myocardial effects that may block adrenergic, hypertrophic, and proapoptotic signaling. Cyclic GMP 37-41 phosphodiesterase 5A Homo sapiens 54-58 18058160-1 2008 It is shown that phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil can modulate pulmonary arterial hypertension (PAH) via increasing the level of guanosine-3,5-cyclic monophosphate (cGMP) and decreases pulmonary artery pressure (PAP). Cyclic GMP 158-192 phosphodiesterase 5A Homo sapiens 17-41 18058160-1 2008 It is shown that phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil can modulate pulmonary arterial hypertension (PAH) via increasing the level of guanosine-3,5-cyclic monophosphate (cGMP) and decreases pulmonary artery pressure (PAP). Cyclic GMP 158-192 phosphodiesterase 5A Homo sapiens 43-47 18058160-1 2008 It is shown that phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil can modulate pulmonary arterial hypertension (PAH) via increasing the level of guanosine-3,5-cyclic monophosphate (cGMP) and decreases pulmonary artery pressure (PAP). Cyclic GMP 194-198 phosphodiesterase 5A Homo sapiens 17-41 18058160-1 2008 It is shown that phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil can modulate pulmonary arterial hypertension (PAH) via increasing the level of guanosine-3,5-cyclic monophosphate (cGMP) and decreases pulmonary artery pressure (PAP). Cyclic GMP 194-198 phosphodiesterase 5A Homo sapiens 43-47 18199808-8 2008 The results suggested that phosphorylation acts in concert with allosteric cGMP binding to stimulate the PDE5 catalytic site, which should promote negative feedback regulation of the cGMP pathway in intact cells. Cyclic GMP 75-79 phosphodiesterase 5A Homo sapiens 105-109 18199808-8 2008 The results suggested that phosphorylation acts in concert with allosteric cGMP binding to stimulate the PDE5 catalytic site, which should promote negative feedback regulation of the cGMP pathway in intact cells. Cyclic GMP 183-187 phosphodiesterase 5A Homo sapiens 105-109 18293931-0 2008 The GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5) is a sensor and a sink for cGMP. Cyclic GMP 36-40 phosphodiesterase 5A Homo sapiens 69-73 18293931-1 2008 We describe here a novel sensor for cGMP based on the GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase 5 (PDE5) using bioluminescence resonance energy transfer (BRET). Cyclic GMP 36-40 phosphodiesterase 5A Homo sapiens 121-125 18293931-1 2008 We describe here a novel sensor for cGMP based on the GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase 5 (PDE5) using bioluminescence resonance energy transfer (BRET). Cyclic GMP 72-76 phosphodiesterase 5A Homo sapiens 121-125 18293931-6 2008 The tandem GAF domains in full length PDE5 could also sequester cGMP when the catalytic activity of PDE5 was inhibited. Cyclic GMP 64-68 phosphodiesterase 5A Homo sapiens 38-42 18293931-6 2008 The tandem GAF domains in full length PDE5 could also sequester cGMP when the catalytic activity of PDE5 was inhibited. Cyclic GMP 64-68 phosphodiesterase 5A Homo sapiens 100-104 18293931-8 2008 PDE5 is the target for the anti-impotence drug sildenafil citrate; therefore, this GAF-BRET (2) sensor could be used for the identification of novel compounds that inhibit cGMP binding to the GAF domain, thereby regulating PDE5 catalytic activity. Cyclic GMP 172-176 phosphodiesterase 5A Homo sapiens 0-4 18293931-8 2008 PDE5 is the target for the anti-impotence drug sildenafil citrate; therefore, this GAF-BRET (2) sensor could be used for the identification of novel compounds that inhibit cGMP binding to the GAF domain, thereby regulating PDE5 catalytic activity. Cyclic GMP 172-176 phosphodiesterase 5A Homo sapiens 223-227 18165313-8 2008 In contrast, ANP elicited sustained submembrane elevations in [cGMP](i), which were converted to global cGMP elevations by inhibition of PDE-5 by sildenafil. Cyclic GMP 63-67 phosphodiesterase 5A Homo sapiens 137-142 18235020-12 2008 Moreover, the elevated cGMP, from endogenous or exogenous NO, plays a permissive role for sildenafil to exert vasodilation through inhibition of the PDE5 pathway independent of ERK signaling. Cyclic GMP 23-27 phosphodiesterase 5A Homo sapiens 149-153 18204475-0 2008 Contractile agonists attenuate cGMP levels by stimulating phosphorylation of cGMP-specific PDE5; an effect mediated by RhoA/PKC-dependent inhibition of protein phosphatase 1. Cyclic GMP 31-35 phosphodiesterase 5A Homo sapiens 91-95 18204475-0 2008 Contractile agonists attenuate cGMP levels by stimulating phosphorylation of cGMP-specific PDE5; an effect mediated by RhoA/PKC-dependent inhibition of protein phosphatase 1. Cyclic GMP 77-81 phosphodiesterase 5A Homo sapiens 91-95 18204475-1 2008 BACKGROUND AND PURPOSE: In gastrointestinal smooth muscle cGMP levels in response to relaxant agonists are regulated by PKG-mediated phosphorylation and activation of phosphodiesterase 5 (PDE5). Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 167-186 18204475-1 2008 BACKGROUND AND PURPOSE: In gastrointestinal smooth muscle cGMP levels in response to relaxant agonists are regulated by PKG-mediated phosphorylation and activation of phosphodiesterase 5 (PDE5). Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 188-192 18204475-2 2008 The aim of the present study was to determine whether contractile agonists modulate cGMP levels by cross-regulating PDE5 activity and to identify the mechanism of action. Cyclic GMP 84-88 phosphodiesterase 5A Homo sapiens 116-120 17991881-1 2008 In the pulmonary vasculature, cGMP concentrations are regulated in part by a cGMP-dependent phosphodiesterase (PDE), PDE5. Cyclic GMP 30-34 phosphodiesterase 5A Homo sapiens 117-121 17991881-5 2008 We demonstrate that inhibition of PDE5 activity with sildenafil partially rescues cGMP responsiveness to exogenous NO. Cyclic GMP 82-86 phosphodiesterase 5A Homo sapiens 34-38 18165313-8 2008 In contrast, ANP elicited sustained submembrane elevations in [cGMP](i), which were converted to global cGMP elevations by inhibition of PDE-5 by sildenafil. Cyclic GMP 104-108 phosphodiesterase 5A Homo sapiens 137-142 18165313-9 2008 These results indicate that FlincG is an innovative tool to elucidate the dynamics of a central biological signal, cGMP, and that NO and natriuretic peptides induce distinct cGMP patterning under the regulation of PDE-5, and therefore likely differentially engage cGMP targets. Cyclic GMP 174-178 phosphodiesterase 5A Homo sapiens 214-219 18165313-9 2008 These results indicate that FlincG is an innovative tool to elucidate the dynamics of a central biological signal, cGMP, and that NO and natriuretic peptides induce distinct cGMP patterning under the regulation of PDE-5, and therefore likely differentially engage cGMP targets. Cyclic GMP 174-178 phosphodiesterase 5A Homo sapiens 214-219 18282775-11 2008 Inhibitor of cGMP-specific PDE5 (zaprinast; 0.1-10 microM) did not affect eosinophil apoptosis and only slightly increased spontaneous neutrophil apoptosis. Cyclic GMP 13-17 phosphodiesterase 5A Homo sapiens 27-31 18673225-2 2008 cGMP-Phosphodiesterase type 5 (PDE5) hydrolizes cGMP, and the result is smooth muscle contraction. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 31-35 18673225-6 2008 Chemical structures of 438 compounds and their cGMP-PDE5 inhibitory data (IC50) were collected from recently published articles. Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 52-56 17906676-7 2007 PDE-5A is rapidly activated in response to ANP stimulation and lowers intracellular cGMP levels. Cyclic GMP 84-88 phosphodiesterase 5A Homo sapiens 0-6 17979301-1 2007 The molecular bases for phosphodiesterase 5 (PDE5) catalytic-site affinity for cyclic guanosine monophosphate (cGMP) and potency of inhibitors are poorly understood. Cyclic GMP 79-109 phosphodiesterase 5A Homo sapiens 24-43 18040025-3 2007 In disorders such as cardiac failure, PDE5A upregulation may contribute to a decline in cGMP and protein kinase G signaling, exacerbating dysfunction. Cyclic GMP 88-92 phosphodiesterase 5A Homo sapiens 38-43 17979301-1 2007 The molecular bases for phosphodiesterase 5 (PDE5) catalytic-site affinity for cyclic guanosine monophosphate (cGMP) and potency of inhibitors are poorly understood. Cyclic GMP 79-109 phosphodiesterase 5A Homo sapiens 45-49 17979301-1 2007 The molecular bases for phosphodiesterase 5 (PDE5) catalytic-site affinity for cyclic guanosine monophosphate (cGMP) and potency of inhibitors are poorly understood. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 24-43 17979301-1 2007 The molecular bases for phosphodiesterase 5 (PDE5) catalytic-site affinity for cyclic guanosine monophosphate (cGMP) and potency of inhibitors are poorly understood. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 45-49 17979301-12 2007 The results quantify the role of PDE5 catalytic-site residues for cGMP and inhibitors, indicate that Tyr-612, Gln-817, and Phe-820 are the most important cGMP or inhibitor contacts studied, and identify residues that contribute to selectivity among different classes of inhibitors. Cyclic GMP 66-70 phosphodiesterase 5A Homo sapiens 33-37 17979301-12 2007 The results quantify the role of PDE5 catalytic-site residues for cGMP and inhibitors, indicate that Tyr-612, Gln-817, and Phe-820 are the most important cGMP or inhibitor contacts studied, and identify residues that contribute to selectivity among different classes of inhibitors. Cyclic GMP 154-158 phosphodiesterase 5A Homo sapiens 33-37 17728050-11 2007 Several possible mechanisms could explain effectiveness of the PDE5-Is for treatment of PE: centrally, through the effect on the nitric oxide/cyclic guanosine monophosphate pathway; peripherally by causing relaxation of smooth muscle in the vas deferens, seminal vesicles, prostate, and urethra and inhibition of adrenergic transmission; or locally by inducing peripheral analgesia. Cyclic GMP 142-172 phosphodiesterase 5A Homo sapiens 63-67 17690252-1 2007 Phosphodiesterase-5 (PDE5) specifically hydrolyzes cGMP, thereby contributing to modulation of intracellular levels of this nucleotide. Cyclic GMP 51-55 phosphodiesterase 5A Homo sapiens 0-19 17625575-3 2007 The safety and high tolerability of PDE5 inhibitors make them an attractive tool to investigate further physiological functions of PDE5, for example the modulation of intracellular cyclic GMP (cGMP) pools. Cyclic GMP 193-197 phosphodiesterase 5A Homo sapiens 36-40 17625575-3 2007 The safety and high tolerability of PDE5 inhibitors make them an attractive tool to investigate further physiological functions of PDE5, for example the modulation of intracellular cyclic GMP (cGMP) pools. Cyclic GMP 193-197 phosphodiesterase 5A Homo sapiens 131-135 17690252-1 2007 Phosphodiesterase-5 (PDE5) specifically hydrolyzes cGMP, thereby contributing to modulation of intracellular levels of this nucleotide. Cyclic GMP 51-55 phosphodiesterase 5A Homo sapiens 21-25 17690252-2 2007 In the present study, preincubation with cGMP increased PDE5 catalytic activity for cGMP degradation, and it converted the PDE5 catalytic site to a form that was more potently inhibited by each of the three PDE5 catalytic site-specific inhibitors: sildenafil, vardenafil, and tadalafil. Cyclic GMP 41-45 phosphodiesterase 5A Homo sapiens 56-60 17690252-2 2007 In the present study, preincubation with cGMP increased PDE5 catalytic activity for cGMP degradation, and it converted the PDE5 catalytic site to a form that was more potently inhibited by each of the three PDE5 catalytic site-specific inhibitors: sildenafil, vardenafil, and tadalafil. Cyclic GMP 41-45 phosphodiesterase 5A Homo sapiens 123-127 17690252-2 2007 In the present study, preincubation with cGMP increased PDE5 catalytic activity for cGMP degradation, and it converted the PDE5 catalytic site to a form that was more potently inhibited by each of the three PDE5 catalytic site-specific inhibitors: sildenafil, vardenafil, and tadalafil. Cyclic GMP 41-45 phosphodiesterase 5A Homo sapiens 123-127 17690252-2 2007 In the present study, preincubation with cGMP increased PDE5 catalytic activity for cGMP degradation, and it converted the PDE5 catalytic site to a form that was more potently inhibited by each of the three PDE5 catalytic site-specific inhibitors: sildenafil, vardenafil, and tadalafil. Cyclic GMP 84-88 phosphodiesterase 5A Homo sapiens 56-60 17690252-3 2007 These results implied that elevated cGMP initiates a physiological negative feedback on the cGMP pathway by increasing the affinity of the PDE5 catalytic site for cGMP. Cyclic GMP 36-40 phosphodiesterase 5A Homo sapiens 139-143 17690252-3 2007 These results implied that elevated cGMP initiates a physiological negative feedback on the cGMP pathway by increasing the affinity of the PDE5 catalytic site for cGMP. Cyclic GMP 92-96 phosphodiesterase 5A Homo sapiens 139-143 17690252-3 2007 These results implied that elevated cGMP initiates a physiological negative feedback on the cGMP pathway by increasing the affinity of the PDE5 catalytic site for cGMP. Cyclic GMP 92-96 phosphodiesterase 5A Homo sapiens 139-143 17690252-4 2007 This increase in catalytic site activity or affinity for inhibitors could be caused by binding of cGMP to either the PDE5 allosteric sites, catalytic site, or both. Cyclic GMP 98-102 phosphodiesterase 5A Homo sapiens 117-121 17690252-8 2007 Studies of amino-terminally truncated PDE5 established that full-length mammalian GAF-B (cGMP-binding phosphodiesterase, Anabaena adenylyl cyclases, Escherichia coli FhlA) subdomain conjoined with the catalytic domain was sufficient for this conversion. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 38-42 17691956-3 2007 Chemical inhibition of PDE5 by sildenafil, tadalafil or vardenafil recently became a valid therapeutic option aimed at overexpressing the molecular pathway originated from nitric oxide and expressed via increased cell cGMP availability. Cyclic GMP 218-222 phosphodiesterase 5A Homo sapiens 23-27 17383621-0 2007 Celecoxib dilates guinea-pig coronaries and rat aortic rings and amplifies NO/cGMP signaling by PDE5 inhibition. Cyclic GMP 78-82 phosphodiesterase 5A Homo sapiens 96-100 17467673-3 2007 Growing evidence supports an important role of several PDEs, including PDE1, PDE2, and PDE5, in the regulation of cGMP in both vascular smooth muscle and cardiac myocytes. Cyclic GMP 114-118 phosphodiesterase 5A Homo sapiens 87-91 17467673-8 2007 Recent studies utilizing selective PDE5 inhibitors support significant cross-signaling with NO-cGMP synthetic pathways that may be particularly helpful in treating certain disease states. Cyclic GMP 95-99 phosphodiesterase 5A Homo sapiens 35-39 17207606-12 2007 The kinetic characteristics of these cGMP peaks were governed by the concerted action of the NO-sensitive guanylyl cyclase (GC) and phosphodiesterase type V (PDE5) as shown by their respective inhibition using 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and Sildenafil. Cyclic GMP 37-41 phosphodiesterase 5A Homo sapiens 158-162 17207606-13 2007 These responses occurred in the presence of moderately elevated cGMP (5-15% FRET ratio), and thus activated PKG and phosphorylated PDE5, suggesting a prominent role for GC in the maintenance and termination of cGMP peaks. Cyclic GMP 210-214 phosphodiesterase 5A Homo sapiens 131-135 17207606-14 2007 Furthermore, cGMP transients could be elicited repeatedly without apparent desensitization of GC or by suppression of cGMP via long-term PDE5 activity. Cyclic GMP 13-17 phosphodiesterase 5A Homo sapiens 137-141 17207606-14 2007 Furthermore, cGMP transients could be elicited repeatedly without apparent desensitization of GC or by suppression of cGMP via long-term PDE5 activity. Cyclic GMP 118-122 phosphodiesterase 5A Homo sapiens 137-141 17138653-8 2007 However, blocking PDE5 with vardenafil increased SNP antiproliferative and relaxant activity up to the level observed with SP-8-Br-PET-cGMPS. Cyclic GMP 135-140 phosphodiesterase 5A Homo sapiens 18-22 17138653-13 2007 Overall, these results demonstrate that PDE5 regulates bladder smooth muscle tone, strongly limiting the nitric oxide/cGMP signaling, and that vardenafil, by blocking PDE5, may be a possible therapeutic option for bladder dysfunction by ameliorating irritative lower urinary tract symptoms. Cyclic GMP 118-122 phosphodiesterase 5A Homo sapiens 40-44 17102958-9 2007 Our results indicate that PDE5 inhibitors can reverse the tension of isolated human ureteral smooth muscle via cGMP-mediated pathways. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 26-30 17305584-1 2007 PDE5 is a key enzyme involved in the regulation of cGMP-specific signaling pathways in normal physiological processes such as smooth muscle contraction and relaxation. Cyclic GMP 51-55 phosphodiesterase 5A Homo sapiens 0-4 17305584-6 2007 Inhibition of PDE5 that results in sustained increases in [cGMP](i) are required to modify the process of apoptosis and mitotic arrest in those carcinoma cells with enhanced PDE5 expressions. Cyclic GMP 59-63 phosphodiesterase 5A Homo sapiens 14-18 17305584-6 2007 Inhibition of PDE5 that results in sustained increases in [cGMP](i) are required to modify the process of apoptosis and mitotic arrest in those carcinoma cells with enhanced PDE5 expressions. Cyclic GMP 59-63 phosphodiesterase 5A Homo sapiens 174-178 17209664-4 2007 NO and phosphodiesterase type 5 (PDE5) inhibitors induce pulmonary vasodilation by increasing intracellular cyclic guanosine monophosphate (cGMP) concentrations. Cyclic GMP 108-138 phosphodiesterase 5A Homo sapiens 7-31 17209664-4 2007 NO and phosphodiesterase type 5 (PDE5) inhibitors induce pulmonary vasodilation by increasing intracellular cyclic guanosine monophosphate (cGMP) concentrations. Cyclic GMP 108-138 phosphodiesterase 5A Homo sapiens 33-37 17209664-4 2007 NO and phosphodiesterase type 5 (PDE5) inhibitors induce pulmonary vasodilation by increasing intracellular cyclic guanosine monophosphate (cGMP) concentrations. Cyclic GMP 140-144 phosphodiesterase 5A Homo sapiens 7-31 17209664-4 2007 NO and phosphodiesterase type 5 (PDE5) inhibitors induce pulmonary vasodilation by increasing intracellular cyclic guanosine monophosphate (cGMP) concentrations. Cyclic GMP 140-144 phosphodiesterase 5A Homo sapiens 33-37 17659276-6 2007 cyclic GMP (cGMP)-hydrolyzing activity declines by about half after differentiation to myofibroblasts in all pulmonary fibroblasts investigated, which is accompanied by a down-regulation of PDE5 protein. Cyclic GMP 0-10 phosphodiesterase 5A Homo sapiens 190-194 17659276-6 2007 cyclic GMP (cGMP)-hydrolyzing activity declines by about half after differentiation to myofibroblasts in all pulmonary fibroblasts investigated, which is accompanied by a down-regulation of PDE5 protein. Cyclic GMP 12-16 phosphodiesterase 5A Homo sapiens 190-194 17694282-1 2007 Phosphodiesterase type 5 (PDE5) induces the breakdown of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. Cyclic GMP 57-87 phosphodiesterase 5A Homo sapiens 0-24 17694282-1 2007 Phosphodiesterase type 5 (PDE5) induces the breakdown of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. Cyclic GMP 57-87 phosphodiesterase 5A Homo sapiens 26-30 17694282-1 2007 Phosphodiesterase type 5 (PDE5) induces the breakdown of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 0-24 17694282-1 2007 Phosphodiesterase type 5 (PDE5) induces the breakdown of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 26-30 17694282-2 2007 Hence, PDE5 inhibitors promote vasodilative effects by enhancing intracellular cGMP levels. Cyclic GMP 79-83 phosphodiesterase 5A Homo sapiens 7-11 17606845-6 2007 PDE5 inhibition leads to increases in both cGMP and cAMP in RVH but not normal RV. Cyclic GMP 43-47 phosphodiesterase 5A Homo sapiens 0-4 17606845-7 2007 Protein kinase G activity is suppressed in RVH, explaining why the PDE5 inhibitor-induced increase in cGMP does not lead to inhibition of contractility. Cyclic GMP 102-106 phosphodiesterase 5A Homo sapiens 67-71 17498099-12 2007 CONCLUSIONS: Our results, for the first time, demonstrate the presence of cAMP- and cGMP-PDE isoenzymes in the human labia minora and give a hint to a significance of PDE4 and PDE5 in the control of labial vascular tissue function. Cyclic GMP 84-88 phosphodiesterase 5A Homo sapiens 176-180 16943225-5 2007 cGMP accumulation was readily detected in cultured human RPE cells after incubation with Bay60-7550 as a selective PDE2 inhibitor, sildenafil as a selective PDE5 inhibitor or Sch51866 as a selective PDE9 inhibitor. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 157-161 16943225-8 2007 CONCLUSIONS: PDE2, PDE5 and PDE9 have a role in cGMP metabolism in RPE cells. Cyclic GMP 48-52 phosphodiesterase 5A Homo sapiens 19-23 17691956-2 2007 PDE isoenzyme 5 (PDE5) is specifically involved in cGMP inactivation in the smooth muscle cell. Cyclic GMP 51-55 phosphodiesterase 5A Homo sapiens 0-15 17691956-2 2007 PDE isoenzyme 5 (PDE5) is specifically involved in cGMP inactivation in the smooth muscle cell. Cyclic GMP 51-55 phosphodiesterase 5A Homo sapiens 17-21 17127429-5 2007 The combined results imply that cGMP binding to the catalytic site initiates negative feedback control of many cellular cGMP signaling pathways by directly stimulating phosphorylation and activation of PDE5; by exploiting this molecular mechanism, PDE5 inhibitors stimulate their own potencies. Cyclic GMP 32-36 phosphodiesterase 5A Homo sapiens 202-206 17127429-5 2007 The combined results imply that cGMP binding to the catalytic site initiates negative feedback control of many cellular cGMP signaling pathways by directly stimulating phosphorylation and activation of PDE5; by exploiting this molecular mechanism, PDE5 inhibitors stimulate their own potencies. Cyclic GMP 32-36 phosphodiesterase 5A Homo sapiens 248-252 17127429-5 2007 The combined results imply that cGMP binding to the catalytic site initiates negative feedback control of many cellular cGMP signaling pathways by directly stimulating phosphorylation and activation of PDE5; by exploiting this molecular mechanism, PDE5 inhibitors stimulate their own potencies. Cyclic GMP 120-124 phosphodiesterase 5A Homo sapiens 202-206 17127429-5 2007 The combined results imply that cGMP binding to the catalytic site initiates negative feedback control of many cellular cGMP signaling pathways by directly stimulating phosphorylation and activation of PDE5; by exploiting this molecular mechanism, PDE5 inhibitors stimulate their own potencies. Cyclic GMP 120-124 phosphodiesterase 5A Homo sapiens 248-252 17170606-9 2006 The efficacy of the PDE-5 inhibitors also serves to illustrate the importance of the NO-cGMP pathway in erectile function since these agents counteract the degradation of NO-generated cGMP. Cyclic GMP 88-92 phosphodiesterase 5A Homo sapiens 20-25 17170606-9 2006 The efficacy of the PDE-5 inhibitors also serves to illustrate the importance of the NO-cGMP pathway in erectile function since these agents counteract the degradation of NO-generated cGMP. Cyclic GMP 184-188 phosphodiesterase 5A Homo sapiens 20-25 17146920-0 2006 [Phosphodiesterase type 5 siRNA increases cGMP in the smooth muscle cells of human corpus cavernosum]. Cyclic GMP 42-46 phosphodiesterase 5A Homo sapiens 1-25 16926278-1 2006 Phosphodiesterase-5 (PDE5) contains a catalytic domain (C domain) that hydrolyzes cGMP and a regulatory domain (R domain) that contains two mammalian cGMP-binding phosphodiesterase, Anabaena adenylyl cyclases, Escherichia coli FhlAs (GAFs) (A and B) and a phosphorylation site for cyclic nucleotide-dependent protein kinases (cNPKs). Cyclic GMP 82-86 phosphodiesterase 5A Homo sapiens 0-19 16926278-1 2006 Phosphodiesterase-5 (PDE5) contains a catalytic domain (C domain) that hydrolyzes cGMP and a regulatory domain (R domain) that contains two mammalian cGMP-binding phosphodiesterase, Anabaena adenylyl cyclases, Escherichia coli FhlAs (GAFs) (A and B) and a phosphorylation site for cyclic nucleotide-dependent protein kinases (cNPKs). Cyclic GMP 82-86 phosphodiesterase 5A Homo sapiens 21-25 16926278-2 2006 Binding of cGMP to GAF-A increases cNPK phosphorylation of PDE5 and improves catalytic site affinity for cGMP or inhibitors. Cyclic GMP 11-15 phosphodiesterase 5A Homo sapiens 59-63 16926278-6 2006 K(m) values of the mutants for cGMP were similar to that of full-length PDE5. Cyclic GMP 31-35 phosphodiesterase 5A Homo sapiens 72-76 17146920-1 2006 OBJECTIVE: To investigate the effect of phosphodiesterase type 5 (PDE5) small interfering RNA (siRNA) on the cGMP in the smooth muscle cells of human corpus cavernosum, and to provide an experimental groundwork for the gene therapy of erectile dysfunction (ED). Cyclic GMP 109-113 phosphodiesterase 5A Homo sapiens 40-64 17146920-1 2006 OBJECTIVE: To investigate the effect of phosphodiesterase type 5 (PDE5) small interfering RNA (siRNA) on the cGMP in the smooth muscle cells of human corpus cavernosum, and to provide an experimental groundwork for the gene therapy of erectile dysfunction (ED). Cyclic GMP 109-113 phosphodiesterase 5A Homo sapiens 66-70 16912214-5 2006 The molecular dynamics simulations and QM/MM calculations on PDE5 demonstrate for the first time that the BL2 in PDE5 should also be HO- rather than H2O as proposed in recently published reports on the x-ray crystal structures, which serves as the nucleophile to initialize the PDE5-catalyzed hydrolysis of cGMP. Cyclic GMP 307-311 phosphodiesterase 5A Homo sapiens 61-65 16912214-5 2006 The molecular dynamics simulations and QM/MM calculations on PDE5 demonstrate for the first time that the BL2 in PDE5 should also be HO- rather than H2O as proposed in recently published reports on the x-ray crystal structures, which serves as the nucleophile to initialize the PDE5-catalyzed hydrolysis of cGMP. Cyclic GMP 307-311 phosphodiesterase 5A Homo sapiens 113-117 16912214-5 2006 The molecular dynamics simulations and QM/MM calculations on PDE5 demonstrate for the first time that the BL2 in PDE5 should also be HO- rather than H2O as proposed in recently published reports on the x-ray crystal structures, which serves as the nucleophile to initialize the PDE5-catalyzed hydrolysis of cGMP. Cyclic GMP 307-311 phosphodiesterase 5A Homo sapiens 113-117 16914104-2 2006 Therefore, inhibition of type 5 phosphodiesterase (PDE5), the principle enzyme responsible for cyclic guanosine monophosphate catabolism in the lungs and skeletal muscle, has been targeted in an effort to counteract vasoconstriction that contributes to increased right and LV afterload in HF. Cyclic GMP 95-125 phosphodiesterase 5A Homo sapiens 51-55 16635522-9 2006 Immunoreactivity specific for PDE5 (cyclic guanosine monophosphate-PDE) was limited to the smooth muscle of the clitoral erectile tissue. Cyclic GMP 36-66 phosphodiesterase 5A Homo sapiens 30-34 16431013-4 2006 RESULTS: Chronic administration of PDE-5 inhibitors have reportedly been associated with increased persistent vascular and endothelial function--which represents a key factor in maintaining vascular tone and inducing vasodilation--by increasing the level of endothelial cGMP generated by activation of endothelial nitric oxide. Cyclic GMP 270-274 phosphodiesterase 5A Homo sapiens 35-40 16281046-1 2006 Despite close structural similarity, vardenafil (Levitra) is 32-fold more potent than sildenafil (Viagra) to inhibit cGMP-binding cGMP-specific PDE (PDE5); this is due to differences between their heterocyclic rings. Cyclic GMP 117-121 phosphodiesterase 5A Homo sapiens 149-153 16281046-1 2006 Despite close structural similarity, vardenafil (Levitra) is 32-fold more potent than sildenafil (Viagra) to inhibit cGMP-binding cGMP-specific PDE (PDE5); this is due to differences between their heterocyclic rings. Cyclic GMP 130-134 phosphodiesterase 5A Homo sapiens 149-153 16690614-1 2006 We analyzed cGMP signaling by the human phosphodiesterase 5 (hPDE5) tandem GAF domain based on a functional activation assay. Cyclic GMP 12-16 phosphodiesterase 5A Homo sapiens 61-66 16690614-3 2006 We demonstrate functional coupling between the hPDE5 GAF ensemble and the AC resulting in a chimera stimulated 10-fold by cGMP. Cyclic GMP 122-126 phosphodiesterase 5A Homo sapiens 47-52 16690614-4 2006 The hPDE5 GAF domain has an inhibitory effect on AC activity, which is released upon cGMP activation. Cyclic GMP 85-89 phosphodiesterase 5A Homo sapiens 4-9 16690614-6 2006 The Ser-102 phosphorylation site of hPDE5 increased cGMP affinity, as shown by a 5-fold lower K(D) for cGMP in a S102D mutant, which mimicked complete modification. Cyclic GMP 52-56 phosphodiesterase 5A Homo sapiens 36-41 16690614-6 2006 The Ser-102 phosphorylation site of hPDE5 increased cGMP affinity, as shown by a 5-fold lower K(D) for cGMP in a S102D mutant, which mimicked complete modification. Cyclic GMP 103-107 phosphodiesterase 5A Homo sapiens 36-41 16787138-8 2006 Recent studies also suggest that PDE5 inhibitors may have antihypertropic effects, exerted through increased myocardial cGMP signalling, that could be of additional benefit in patients with heart failure. Cyclic GMP 120-124 phosphodiesterase 5A Homo sapiens 33-37 16510560-3 2006 In these tissues, NO mediates its effects by stimulating guanylyl cyclase (GC) to form cGMP; the subsequent increase in cGMP is counteracted by the cGMP-specific phosphodiesterase (PDE5), which hydrolyzes cGMP. Cyclic GMP 120-124 phosphodiesterase 5A Homo sapiens 181-185 16510560-3 2006 In these tissues, NO mediates its effects by stimulating guanylyl cyclase (GC) to form cGMP; the subsequent increase in cGMP is counteracted by the cGMP-specific phosphodiesterase (PDE5), which hydrolyzes cGMP. Cyclic GMP 120-124 phosphodiesterase 5A Homo sapiens 181-185 16510560-4 2006 In platelets, allosteric activation of PDE5 by cGMP paralleled by phosphorylation has been shown to govern the sensitivity of NO/cGMP signaling. Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 39-43 16510560-4 2006 In platelets, allosteric activation of PDE5 by cGMP paralleled by phosphorylation has been shown to govern the sensitivity of NO/cGMP signaling. Cyclic GMP 129-133 phosphodiesterase 5A Homo sapiens 39-43 16460876-7 2006 In contrast to the distribution of PDE4, immunoactivity indicating PDE5 (cGMP-PDE) and 11 (dual substrate PDE) was mainly observed in glandular and subglandular areas. Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 67-71 17017938-1 2006 Phosphodiesterase 5 (PDE5) is one of eleven members of the mammalian phosphodiesterase family that hydrolyzes cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP). Cyclic GMP 110-140 phosphodiesterase 5A Homo sapiens 0-19 16455054-8 2006 Together, these results suggest that PDE5 regulation of cGMP intracellular levels is not involved in the control of SMC cycle progression, but may represent one of the markers of the contractile phenotype. Cyclic GMP 56-60 phosphodiesterase 5A Homo sapiens 37-41 16407275-8 2006 For PDE5(Q817A), K(m) for cGMP or cAMP was weakened 60- or 2-fold, respectively. Cyclic GMP 26-30 phosphodiesterase 5A Homo sapiens 4-8 16407275-9 2006 For PDE5(Q775A), K(m) for cGMP was weakened approximately 20-fold but was unchanged for cAMP. Cyclic GMP 26-30 phosphodiesterase 5A Homo sapiens 4-8 16407275-12 2006 It is concluded that Gln(817) is a positive determinant for PDE5 affinity for cGMP and several inhibitors; Gln(775), which perhaps restricts rotation of Gln(817) side chain, is critical for cGMP affinity but has no measurable effect on affinity for cAMP, sildenafil, or vardenafil. Cyclic GMP 78-82 phosphodiesterase 5A Homo sapiens 60-64 16498233-2 2006 The main action of sildenafil is the enhancement of the effect of nitric oxide (NO) by inhibiting the cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase-5 (PDE-5), an enzyme responsible for degradation of cGMP. Cyclic GMP 102-132 phosphodiesterase 5A Homo sapiens 170-175 16498233-2 2006 The main action of sildenafil is the enhancement of the effect of nitric oxide (NO) by inhibiting the cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase-5 (PDE-5), an enzyme responsible for degradation of cGMP. Cyclic GMP 134-138 phosphodiesterase 5A Homo sapiens 170-175 16842174-7 2006 PDE5 (cGMP) is involved in early consolidation processes. Cyclic GMP 6-10 phosphodiesterase 5A Homo sapiens 0-4 16458289-10 2006 PDE5 is an inactivator of cGMP and may have beneficial effects on hypoxic pulmonary hypertension and vascular remodelling. Cyclic GMP 26-30 phosphodiesterase 5A Homo sapiens 0-4 16256165-5 2006 The replacement of the PDE6 H-loop into the PDE5 catalytic domain increases the catalytic rate and the K(m) value for cGMP hydrolysis, whereas the substitution of the M-loop produces catalytic PDE domains responsive to Pgamma. Cyclic GMP 118-122 phosphodiesterase 5A Homo sapiens 44-48 17017938-1 2006 Phosphodiesterase 5 (PDE5) is one of eleven members of the mammalian phosphodiesterase family that hydrolyzes cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP). Cyclic GMP 110-140 phosphodiesterase 5A Homo sapiens 21-25 17017938-1 2006 Phosphodiesterase 5 (PDE5) is one of eleven members of the mammalian phosphodiesterase family that hydrolyzes cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP). Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 0-19 17017938-1 2006 Phosphodiesterase 5 (PDE5) is one of eleven members of the mammalian phosphodiesterase family that hydrolyzes cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP). Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 21-25 17017938-2 2006 Best known as the target of the impotence drug sildenafil, PDE5 degrades cGMP in smooth muscle cells so as to maintain the contracted state of contractile organs such as the penis, blood vessels, uterus, and intestines. Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 59-63 16409214-1 2006 Sildenafil citrate improves erectile function in men with erectile dysfunction (ED) by selectively inhibiting cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), which is present in all vascular tissue. Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 183-187 16409221-1 2006 OBJECTIVE: Tadalafil, a long-acting phosphodiesterase type 5 (PDE5) inhibitor, improves the erectile response by inhibiting cyclic guanosine monophosphate (cGMP) breakdown. Cyclic GMP 124-154 phosphodiesterase 5A Homo sapiens 62-66 16409221-1 2006 OBJECTIVE: Tadalafil, a long-acting phosphodiesterase type 5 (PDE5) inhibitor, improves the erectile response by inhibiting cyclic guanosine monophosphate (cGMP) breakdown. Cyclic GMP 156-160 phosphodiesterase 5A Homo sapiens 62-66 16409221-2 2006 Sustained higher levels of cGMP may hypothetically upregulate PDE5 expression and/or activity and lead to tachyphylaxis. Cyclic GMP 27-31 phosphodiesterase 5A Homo sapiens 62-66 17017938-4 2006 Like all other PDEs, PDE5 is dimeric; each subunit is approximately 100 kd in size and has two allosteric cGMP-binding sites and a catalytic domain. Cyclic GMP 106-110 phosphodiesterase 5A Homo sapiens 21-25 17017938-5 2006 Protein kinase G (PKG)-mediated phosphorylation and allosteric cGMP binding upregulate PDE5 activity, while PP1 phosphatase-mediated dephosphorylation downregulates. Cyclic GMP 63-67 phosphodiesterase 5A Homo sapiens 87-91 17017938-10 2006 Both promoters are responsive to cGMP or cAMP stimulation, and several studies have demonstrated regulation of PDE5 expression possibly through these promoters. Cyclic GMP 33-37 phosphodiesterase 5A Homo sapiens 111-115 17017939-1 2006 The discovery that inhibition of phosphodiesterase-5 (PDE5) reduces the degradation of cGMP, allowing erectile function to occur by relaxation of penile smooth muscle, represents a revolutionary approach or the treatment of erectile dysfunction (ED). Cyclic GMP 87-91 phosphodiesterase 5A Homo sapiens 33-52 17017939-1 2006 The discovery that inhibition of phosphodiesterase-5 (PDE5) reduces the degradation of cGMP, allowing erectile function to occur by relaxation of penile smooth muscle, represents a revolutionary approach or the treatment of erectile dysfunction (ED). Cyclic GMP 87-91 phosphodiesterase 5A Homo sapiens 54-58 16236060-3 2005 In fact, beyond the well-known role of T in regulating sexual desire and NO release, recent experimental evidences from our group showed that T also regulates the expression of phosphodiesterase type 5 (PDE5), the hydrolytic enzyme involved in cGMP breakdown. Cyclic GMP 244-248 phosphodiesterase 5A Homo sapiens 177-201 16387563-2 2005 The most prominent target identified thus far is phosphodiesterase 5 (PDE5), which enzymatically converts the intracellular second messenger molecule cyclic guanosine monophosphate (cGMP) to its inactive form. Cyclic GMP 150-180 phosphodiesterase 5A Homo sapiens 49-68 16387563-2 2005 The most prominent target identified thus far is phosphodiesterase 5 (PDE5), which enzymatically converts the intracellular second messenger molecule cyclic guanosine monophosphate (cGMP) to its inactive form. Cyclic GMP 150-180 phosphodiesterase 5A Homo sapiens 70-74 16387563-2 2005 The most prominent target identified thus far is phosphodiesterase 5 (PDE5), which enzymatically converts the intracellular second messenger molecule cyclic guanosine monophosphate (cGMP) to its inactive form. Cyclic GMP 182-186 phosphodiesterase 5A Homo sapiens 49-68 16387563-2 2005 The most prominent target identified thus far is phosphodiesterase 5 (PDE5), which enzymatically converts the intracellular second messenger molecule cyclic guanosine monophosphate (cGMP) to its inactive form. Cyclic GMP 182-186 phosphodiesterase 5A Homo sapiens 70-74 16236060-3 2005 In fact, beyond the well-known role of T in regulating sexual desire and NO release, recent experimental evidences from our group showed that T also regulates the expression of phosphodiesterase type 5 (PDE5), the hydrolytic enzyme involved in cGMP breakdown. Cyclic GMP 244-248 phosphodiesterase 5A Homo sapiens 203-207 16236069-4 2005 PDE5-i represent a class of orally active drugs for ED, which inhibit PDE5 enzyme and in turn enhance smooth muscle relaxation via prolongation of cyclic GMP action within the cavernous smooth muscle. Cyclic GMP 147-157 phosphodiesterase 5A Homo sapiens 0-4 16236069-4 2005 PDE5-i represent a class of orally active drugs for ED, which inhibit PDE5 enzyme and in turn enhance smooth muscle relaxation via prolongation of cyclic GMP action within the cavernous smooth muscle. Cyclic GMP 147-157 phosphodiesterase 5A Homo sapiens 70-74 16185664-2 2005 Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor that potentiates NO action by reducing cGMP breakdown. Cyclic GMP 97-101 phosphodiesterase 5A Homo sapiens 16-40 16273419-15 2005 The findings with regard to the PDE5 inhibitors may indicate that the NO-cGMP pathway is, to a certain degree, involved in the control of vaginal smooth muscle tone. Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 32-36 16292559-15 2005 The expression of the cGMP-specific PDE5 and the ability of the PDE5 inhibitor sildenafil to reverse the adrenergic tension of isolated segments of HCA underline the important role of the NO/cGMP pathway in the control of smooth muscle tone of human trabecular smooth musculature and penile cavernous arteries. Cyclic GMP 22-26 phosphodiesterase 5A Homo sapiens 36-40 16185664-2 2005 Sildenafil is a phosphodiesterase type 5 (PDE5) inhibitor that potentiates NO action by reducing cGMP breakdown. Cyclic GMP 97-101 phosphodiesterase 5A Homo sapiens 42-46 16246060-6 2005 In intact cells, NO-induced cGMP signalling not only depends on cGMP formation, but is also critically determined by the activity of the enzymes responsible for cGMP degradation, e.g. PDE5 (phosphodiesterase 5). Cyclic GMP 28-32 phosphodiesterase 5A Homo sapiens 184-188 16246060-6 2005 In intact cells, NO-induced cGMP signalling not only depends on cGMP formation, but is also critically determined by the activity of the enzymes responsible for cGMP degradation, e.g. PDE5 (phosphodiesterase 5). Cyclic GMP 28-32 phosphodiesterase 5A Homo sapiens 190-209 16246060-7 2005 Recently, direct activation of PDE5 by cGMP was demonstrated, limiting the cGMP increase and thus functioning as a negative feedback. Cyclic GMP 39-43 phosphodiesterase 5A Homo sapiens 31-35 16246060-7 2005 Recently, direct activation of PDE5 by cGMP was demonstrated, limiting the cGMP increase and thus functioning as a negative feedback. Cyclic GMP 75-79 phosphodiesterase 5A Homo sapiens 31-35 16246060-8 2005 As the cGMP-induced PDE5 activation turned out to be sustained, in the range of hours, it is probably responsible for the NO-induced desensitization observed within NO/cGMP signalling. Cyclic GMP 7-11 phosphodiesterase 5A Homo sapiens 20-24 16246060-8 2005 As the cGMP-induced PDE5 activation turned out to be sustained, in the range of hours, it is probably responsible for the NO-induced desensitization observed within NO/cGMP signalling. Cyclic GMP 168-172 phosphodiesterase 5A Homo sapiens 20-24 16246964-1 2005 BACKGROUND: Sildenafil inhibits phosphodiesterase 5 (PDE5A) to elevate intracellular cGMP and to induce vasodilation. Cyclic GMP 85-89 phosphodiesterase 5A Homo sapiens 53-58 16291034-2 2005 Commercially marketed PDE-5 inhibitors are highly specific for PDE-5, and in the face of continuing cyclic GMP (cGMP) synthesis,elevate cellular cGMP. Cyclic GMP 100-110 phosphodiesterase 5A Homo sapiens 22-27 16291034-2 2005 Commercially marketed PDE-5 inhibitors are highly specific for PDE-5, and in the face of continuing cyclic GMP (cGMP) synthesis,elevate cellular cGMP. Cyclic GMP 112-116 phosphodiesterase 5A Homo sapiens 22-27 16291034-2 2005 Commercially marketed PDE-5 inhibitors are highly specific for PDE-5, and in the face of continuing cyclic GMP (cGMP) synthesis,elevate cellular cGMP. Cyclic GMP 145-149 phosphodiesterase 5A Homo sapiens 22-27 15907910-1 2005 Phosphodiesterase-5 (PDE5) inhibitors and other agents that modulate intracellular cGMP are now emerging as promising, safe, and easy to administer therapies for pulmonary hypertension, with relatively few side effects. Cyclic GMP 83-87 phosphodiesterase 5A Homo sapiens 0-19 16157016-2 2005 cGMP-specific phosphodiesterase type 5 (PDE5) inhibitor increases intracellular cGMP levels. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 40-44 16157016-2 2005 cGMP-specific phosphodiesterase type 5 (PDE5) inhibitor increases intracellular cGMP levels. Cyclic GMP 80-84 phosphodiesterase 5A Homo sapiens 40-44 16157016-13 2005 CONCLUSIONS: The PDE5 inhibitor zaprinast may selectively increase CBF in the ischemic brain via increased cGMP levels, thus providing a new strategy against acute cerebral infarction. Cyclic GMP 107-111 phosphodiesterase 5A Homo sapiens 17-21 16080974-3 2005 Aim of this prospective study was to determine whether the combination of iNO plus dipyridamole (DP), a cyclic guanosine monophosphate-specific phosphodiesterase inhibitor (PDE5), may enhance and/or prolong the response to iNO in adult patients with secondary valve-related PH undergoing cardiac surgery, and attenuate rebound events related to its discontinuation. Cyclic GMP 104-134 phosphodiesterase 5A Homo sapiens 173-177 15792963-2 2005 We now report that a cGMP-specific phosphodiesterase, PDE5, plays a dominant role in regulating [cGMP]i transitions that inhibit cell growth and control susceptibility to apoptosis in pulmonary endothelium. Cyclic GMP 21-25 phosphodiesterase 5A Homo sapiens 54-58 15792963-2 2005 We now report that a cGMP-specific phosphodiesterase, PDE5, plays a dominant role in regulating [cGMP]i transitions that inhibit cell growth and control susceptibility to apoptosis in pulmonary endothelium. Cyclic GMP 97-101 phosphodiesterase 5A Homo sapiens 54-58 15792963-4 2005 However, increased [cGMP]i in PAECs is transient and decays within 10 min due to cytosolic PDE5 hydrolytic activity. Cyclic GMP 20-24 phosphodiesterase 5A Homo sapiens 91-95 15792963-6 2005 Indeed, at any ANP concentration, the sustained (30 min) [cGMP]i rise is greater in PMVECs than in PAECs, unless PAECs are also treated with the PDE5 inhibitor zaprinast. Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 145-149 15792963-11 2005 Collectively, these data suggest that PDE5-regulated [cGMP]i controls endothelial cell growth and apoptosis, representing a mechanism of heterogeneity between two endothelial phenotypes. Cyclic GMP 54-58 phosphodiesterase 5A Homo sapiens 38-42 16042713-3 2005 Conversely, selective inhibition of the enzyme that catalyses the degradation of cGMP (phosphodiesterase type 5, PDE-5) promotes erectile responses to sexual stimulation. Cyclic GMP 81-85 phosphodiesterase 5A Homo sapiens 113-118 15817798-7 2005 Most cyclic guanosine monophosphate hydrolysis (about 80%) in cultured cells was attributed to PDE5. Cyclic GMP 5-35 phosphodiesterase 5A Homo sapiens 95-99 15817798-9 2005 Dual stimulation of soluble guanylyl cyclase and inhibition of PDE5 activities also had significant downstream effects, increasing phosphorylation of vasodilator-stimulated phosphoprotein, reducing DNA synthesis and cell proliferation, and stimulating apoptosis, and these effects were mimicked by cyclic guanosine monophosphate analogs. Cyclic GMP 298-328 phosphodiesterase 5A Homo sapiens 63-67 15817798-10 2005 CONCLUSIONS: Phosphodiesterase Type 5 is the main factor regulating cyclic guanosine monophosphate hydrolysis and downstream signaling in human PASMCs. Cyclic GMP 68-98 phosphodiesterase 5A Homo sapiens 13-37 15907910-1 2005 Phosphodiesterase-5 (PDE5) inhibitors and other agents that modulate intracellular cGMP are now emerging as promising, safe, and easy to administer therapies for pulmonary hypertension, with relatively few side effects. Cyclic GMP 83-87 phosphodiesterase 5A Homo sapiens 21-25 15907910-3 2005 In addition, studies on animals reveal that PDE5 inhibitors work in concert with nitric oxide and/or natriuretic peptide levels by enhancing intracellular cGMP and cGMP-mediated vasodilator effects. Cyclic GMP 155-159 phosphodiesterase 5A Homo sapiens 44-48 15907910-3 2005 In addition, studies on animals reveal that PDE5 inhibitors work in concert with nitric oxide and/or natriuretic peptide levels by enhancing intracellular cGMP and cGMP-mediated vasodilator effects. Cyclic GMP 164-168 phosphodiesterase 5A Homo sapiens 44-48 15907910-4 2005 Further, the combination of PDE5 inhibitors and agents that increase cGMP or cAMP also yields additive beneficial effects on pulmonary hemodynamics in patients with pulmonary arterial hypertension. Cyclic GMP 69-73 phosphodiesterase 5A Homo sapiens 28-32 15888841-2 2005 However, these beneficial effects of inhaled NO are limited in magnitude and duration, at least in part due to cGMP hydrolysis by the type 5 isoform of phosphodiesterase (PDE5). Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 171-175 15613622-0 2005 Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites. Cyclic GMP 14-18 phosphodiesterase 5A Homo sapiens 28-52 15951732-7 2005 The NO formation, and therefore the erection, is strictly controlled by the activity of NO synthase (NOS) isoenzymes, whereas cGMP degradation is specifically controlled by phosphodiesterase type 5 (PDE5), which promotes smooth muscle tone and terminates erection. Cyclic GMP 126-130 phosphodiesterase 5A Homo sapiens 173-197 15951732-7 2005 The NO formation, and therefore the erection, is strictly controlled by the activity of NO synthase (NOS) isoenzymes, whereas cGMP degradation is specifically controlled by phosphodiesterase type 5 (PDE5), which promotes smooth muscle tone and terminates erection. Cyclic GMP 126-130 phosphodiesterase 5A Homo sapiens 199-203 15769620-5 2005 Moreover, I will propose that cGMP-mediated effects on the activities of variants of the Phosphodiesterase 2 (PDE2), PDE3 and PDE5 families may act to coordinate linkage between cAMP and cGMP signaling in these cells. Cyclic GMP 30-34 phosphodiesterase 5A Homo sapiens 126-130 15769620-5 2005 Moreover, I will propose that cGMP-mediated effects on the activities of variants of the Phosphodiesterase 2 (PDE2), PDE3 and PDE5 families may act to coordinate linkage between cAMP and cGMP signaling in these cells. Cyclic GMP 187-191 phosphodiesterase 5A Homo sapiens 126-130 15769623-4 2005 In intact cells, NO-induced cGMP signaling not only depends on cGMP formation but is also critically determined by the activity of the enzyme responsible for cGMP degradation, e.g. phosphodiesterase 5 (PDE5). Cyclic GMP 28-32 phosphodiesterase 5A Homo sapiens 181-200 15769623-4 2005 In intact cells, NO-induced cGMP signaling not only depends on cGMP formation but is also critically determined by the activity of the enzyme responsible for cGMP degradation, e.g. phosphodiesterase 5 (PDE5). Cyclic GMP 28-32 phosphodiesterase 5A Homo sapiens 202-206 15769623-5 2005 Sustained activation of PDE5 by cGMP has been identified as the mechanism responsible for the recently observed feedback inhibition within NO/cGMP signaling. Cyclic GMP 32-36 phosphodiesterase 5A Homo sapiens 24-28 15769623-5 2005 Sustained activation of PDE5 by cGMP has been identified as the mechanism responsible for the recently observed feedback inhibition within NO/cGMP signaling. Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 24-28 15769623-6 2005 Moreover, tuning of PDE5 activity may also represent a regulatory link to mediate cross talk between NO-induced and natriuretic peptide-induced cGMP signaling in general. Cyclic GMP 144-148 phosphodiesterase 5A Homo sapiens 20-24 15526282-10 2005 These data substantiate a pivotal role for PDE5 as a modulator of apoptosis and cell-cycle progression for human carcinoma via a mechanism involving the activation of [cGMP]i/PKG signaling pathways. Cyclic GMP 168-172 phosphodiesterase 5A Homo sapiens 43-47 15820939-3 2005 Sildenafil citrate is a selective and potent inhibitor of cGMP-specific phosphodiesterase-5 (PDE5) which promotes selective smooth muscle relaxation in lung vasculature and has been utilized successfully in the treatment of PH. Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 93-97 15567064-2 2005 The cGMP-PDE5 inhibitors Sildenafil and Zaprinast have been demonstrated to potentiate the anti-platelet aggregatory effect of NO donors like sodium nitroprusside (SNP) in vitro but the mechanisms of Sildenafil"s action on the secretory function of human platelets have not been analysed in detail. Cyclic GMP 4-8 phosphodiesterase 5A Homo sapiens 9-13 15640438-2 2005 We now report evidence on VD expression of phosphodiesterase type 5 (PDE5), which regulates nitric oxide (NO)-induced relaxation and cGMP breakdown in smooth muscle cells. Cyclic GMP 133-137 phosphodiesterase 5A Homo sapiens 43-67 15640438-2 2005 We now report evidence on VD expression of phosphodiesterase type 5 (PDE5), which regulates nitric oxide (NO)-induced relaxation and cGMP breakdown in smooth muscle cells. Cyclic GMP 133-137 phosphodiesterase 5A Homo sapiens 69-73 15640438-6 2005 Based on the rank order of potency of these PDE inhibitors, we found that the cGMP metabolizing activity in human VD mostly corresponds to PDE5. Cyclic GMP 78-82 phosphodiesterase 5A Homo sapiens 139-143 15640438-9 2005 In fact, the sensitivity to a NO-donor (NCX4040), its enhancement by PDE5 inhibitors and the PDE5-related cGMP breakdown were all affected by androgen manipulation. Cyclic GMP 106-110 phosphodiesterase 5A Homo sapiens 93-97 15677448-1 2005 The cGMP-binding cGMP-specific phosphodiesterase (PDE5) contains a catalytic domain that hydrolyzes cGMP and a regulatory (R) domain that contains two GAFs (a and b; GAF is derived from the proteins mammalian cGMP-binding PDEs, Anabaena adenylyl cyclases, and Escherichia coli (FhlA)). Cyclic GMP 4-8 phosphodiesterase 5A Homo sapiens 50-54 15677448-1 2005 The cGMP-binding cGMP-specific phosphodiesterase (PDE5) contains a catalytic domain that hydrolyzes cGMP and a regulatory (R) domain that contains two GAFs (a and b; GAF is derived from the proteins mammalian cGMP-binding PDEs, Anabaena adenylyl cyclases, and Escherichia coli (FhlA)). Cyclic GMP 17-21 phosphodiesterase 5A Homo sapiens 50-54 15677448-1 2005 The cGMP-binding cGMP-specific phosphodiesterase (PDE5) contains a catalytic domain that hydrolyzes cGMP and a regulatory (R) domain that contains two GAFs (a and b; GAF is derived from the proteins mammalian cGMP-binding PDEs, Anabaena adenylyl cyclases, and Escherichia coli (FhlA)). Cyclic GMP 17-21 phosphodiesterase 5A Homo sapiens 50-54 15677448-5 2005 Results yield new insights into PDE5 functions, further define boundaries that provide for allosteric cGMP binding, and identify regions that contribute to dimerization. Cyclic GMP 102-106 phosphodiesterase 5A Homo sapiens 32-36 15526282-1 2005 Phosphodiesterase 5 (PDE5) is a major isoform of cGMP phosphodiesterase in a variety of human tumor cell lines and plays a key role in regulating intracellular cGMP concentrations ([cGMP]i). Cyclic GMP 49-53 phosphodiesterase 5A Homo sapiens 0-19 15526282-1 2005 Phosphodiesterase 5 (PDE5) is a major isoform of cGMP phosphodiesterase in a variety of human tumor cell lines and plays a key role in regulating intracellular cGMP concentrations ([cGMP]i). Cyclic GMP 49-53 phosphodiesterase 5A Homo sapiens 21-25 15526282-1 2005 Phosphodiesterase 5 (PDE5) is a major isoform of cGMP phosphodiesterase in a variety of human tumor cell lines and plays a key role in regulating intracellular cGMP concentrations ([cGMP]i). Cyclic GMP 160-164 phosphodiesterase 5A Homo sapiens 0-19 15526282-1 2005 Phosphodiesterase 5 (PDE5) is a major isoform of cGMP phosphodiesterase in a variety of human tumor cell lines and plays a key role in regulating intracellular cGMP concentrations ([cGMP]i). Cyclic GMP 160-164 phosphodiesterase 5A Homo sapiens 21-25 15526282-2 2005 Here, we demonstrate that suppression of PDE5 gene expression by antisense pZeoSV2/ASP5 plasmid transfection results in a sustained increase in [cGMP]i, growth inhibition, and apoptosis in human colon tumor HT29 cells. Cyclic GMP 145-149 phosphodiesterase 5A Homo sapiens 41-45 15526282-6 2005 These results corroborate previous findings with the PDE5 inhibitor exisulind and its derivatives showing that sustained [cGMP]i induces apoptosis and growth inhibition in tumor cells. Cyclic GMP 122-126 phosphodiesterase 5A Homo sapiens 53-57 16339700-3 2005 Sildenafil citrate is a selective and potent inhibitor of cGMP-specific phosphodiesterase-5 (PDE5), which promotes selective smooth muscle relaxation in lung vasculature and has been used successfully in the treatment of PH. Cyclic GMP 58-62 phosphodiesterase 5A Homo sapiens 93-97 16760638-3 2005 PDE5 is in fact the major cGMP hydrolizing enzyme in penile corpus cavernosum. Cyclic GMP 26-30 phosphodiesterase 5A Homo sapiens 0-4 16156423-1 2005 Inhibition of phosphodiesterase-5 (PDE5) reduces the degradation of cyclic guanosine monophosphate, which allows erectile function to occur by relaxation of penile smooth muscle. Cyclic GMP 68-98 phosphodiesterase 5A Homo sapiens 14-33 16156423-1 2005 Inhibition of phosphodiesterase-5 (PDE5) reduces the degradation of cyclic guanosine monophosphate, which allows erectile function to occur by relaxation of penile smooth muscle. Cyclic GMP 68-98 phosphodiesterase 5A Homo sapiens 35-39 15229623-8 2004 Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates NO-cGMP-mediated smooth muscle relaxation. Cyclic GMP 65-69 phosphodiesterase 5A Homo sapiens 0-19 16036043-1 2004 The availability of selective inhibitors of the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE5) has created increasing interest in unlocking the therapeutic potential of PDE5 inhibition in cardiovascular diseases that are marked by dysfunction of nitric oxide (NO)-cGMP signaling. Cyclic GMP 48-78 phosphodiesterase 5A Homo sapiens 121-125 16036043-1 2004 The availability of selective inhibitors of the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE5) has created increasing interest in unlocking the therapeutic potential of PDE5 inhibition in cardiovascular diseases that are marked by dysfunction of nitric oxide (NO)-cGMP signaling. Cyclic GMP 48-78 phosphodiesterase 5A Homo sapiens 201-205 16036043-1 2004 The availability of selective inhibitors of the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE5) has created increasing interest in unlocking the therapeutic potential of PDE5 inhibition in cardiovascular diseases that are marked by dysfunction of nitric oxide (NO)-cGMP signaling. Cyclic GMP 80-84 phosphodiesterase 5A Homo sapiens 121-125 16036043-1 2004 The availability of selective inhibitors of the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE5) has created increasing interest in unlocking the therapeutic potential of PDE5 inhibition in cardiovascular diseases that are marked by dysfunction of nitric oxide (NO)-cGMP signaling. Cyclic GMP 80-84 phosphodiesterase 5A Homo sapiens 201-205 16036043-1 2004 The availability of selective inhibitors of the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE5) has created increasing interest in unlocking the therapeutic potential of PDE5 inhibition in cardiovascular diseases that are marked by dysfunction of nitric oxide (NO)-cGMP signaling. Cyclic GMP 296-300 phosphodiesterase 5A Homo sapiens 121-125 15988068-2 2005 Phosphodiesterase-5 (PDE5), which is highly specific for guanosine 3"-5"-cyclic-monophosphate (cGMP) at both its catalytic site and its allosteric sites, has generated particular interest because it is potently and specifically inhibited by three drugs: sildenafil (Viagra, Pfizer), tadalafil (Cialis, Lilly-ICOS), and vardenafil (Levitra, Bayer GSK). Cyclic GMP 57-93 phosphodiesterase 5A Homo sapiens 0-19 15988068-2 2005 Phosphodiesterase-5 (PDE5), which is highly specific for guanosine 3"-5"-cyclic-monophosphate (cGMP) at both its catalytic site and its allosteric sites, has generated particular interest because it is potently and specifically inhibited by three drugs: sildenafil (Viagra, Pfizer), tadalafil (Cialis, Lilly-ICOS), and vardenafil (Levitra, Bayer GSK). Cyclic GMP 57-93 phosphodiesterase 5A Homo sapiens 21-25 15988068-2 2005 Phosphodiesterase-5 (PDE5), which is highly specific for guanosine 3"-5"-cyclic-monophosphate (cGMP) at both its catalytic site and its allosteric sites, has generated particular interest because it is potently and specifically inhibited by three drugs: sildenafil (Viagra, Pfizer), tadalafil (Cialis, Lilly-ICOS), and vardenafil (Levitra, Bayer GSK). Cyclic GMP 95-99 phosphodiesterase 5A Homo sapiens 0-19 15988068-2 2005 Phosphodiesterase-5 (PDE5), which is highly specific for guanosine 3"-5"-cyclic-monophosphate (cGMP) at both its catalytic site and its allosteric sites, has generated particular interest because it is potently and specifically inhibited by three drugs: sildenafil (Viagra, Pfizer), tadalafil (Cialis, Lilly-ICOS), and vardenafil (Levitra, Bayer GSK). Cyclic GMP 95-99 phosphodiesterase 5A Homo sapiens 21-25 15988068-3 2005 Previously, we have used [(3)H]cGMP to directly study the interaction of cGMP with the allosteric sites of PDE5, but because cGMP binds with relatively low affinity to the catalytic site, it has been difficult to devise a binding assay for this particular binding reaction. Cyclic GMP 31-35 phosphodiesterase 5A Homo sapiens 107-111 15988068-3 2005 Previously, we have used [(3)H]cGMP to directly study the interaction of cGMP with the allosteric sites of PDE5, but because cGMP binds with relatively low affinity to the catalytic site, it has been difficult to devise a binding assay for this particular binding reaction. Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 107-111 15988068-3 2005 Previously, we have used [(3)H]cGMP to directly study the interaction of cGMP with the allosteric sites of PDE5, but because cGMP binds with relatively low affinity to the catalytic site, it has been difficult to devise a binding assay for this particular binding reaction. Cyclic GMP 73-77 phosphodiesterase 5A Homo sapiens 107-111 16095162-6 2005 cGMP is hydrolyzed by 5-phopshodiesterase (PDE-5). Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 43-48 16208781-4 2005 Sildenafil citrate, the specific inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE 5) was studied as an antianginal drug during the late 1980s, but is now used for its effect on erectile function in men. Cyclic GMP 46-76 phosphodiesterase 5A Homo sapiens 119-124 16208781-4 2005 Sildenafil citrate, the specific inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE 5) was studied as an antianginal drug during the late 1980s, but is now used for its effect on erectile function in men. Cyclic GMP 78-82 phosphodiesterase 5A Homo sapiens 119-124 15271668-2 2004 In this study, we examined whether cAMP can enhance or reduce NO-induced cerebral vasodilation in vivo via interfering with cGMP efflux or through potentiating phosphodiesterase 5 (PDE5)-mediated cGMP breakdown, respectively, in cerebral vascular smooth muscle cells (CVSMCs). Cyclic GMP 196-200 phosphodiesterase 5A Homo sapiens 181-185 15271668-10 2004 On the other, cAMP appears to enhance PDE5-mediated cGMP breakdown. Cyclic GMP 52-56 phosphodiesterase 5A Homo sapiens 38-42 16036043-1 2004 The availability of selective inhibitors of the cyclic guanosine monophosphate (cGMP)-specific type 5 phosphodiesterase (PDE5) has created increasing interest in unlocking the therapeutic potential of PDE5 inhibition in cardiovascular diseases that are marked by dysfunction of nitric oxide (NO)-cGMP signaling. Cyclic GMP 296-300 phosphodiesterase 5A Homo sapiens 201-205 16036043-3 2004 PDE5 is abundant in the pulmonary vasculature where it catabolizes cGMP, the second messenger of NO. Cyclic GMP 67-71 phosphodiesterase 5A Homo sapiens 0-4 16036043-4 2004 Inhibition of PDE5 has been shown to lower pulmonary vascular resistance in PAH and HF by augmenting local cGMP. Cyclic GMP 107-111 phosphodiesterase 5A Homo sapiens 14-18 15229623-8 2004 Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates NO-cGMP-mediated smooth muscle relaxation. Cyclic GMP 39-43 phosphodiesterase 5A Homo sapiens 0-19 15229623-8 2004 Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates NO-cGMP-mediated smooth muscle relaxation. Cyclic GMP 39-43 phosphodiesterase 5A Homo sapiens 21-25 15229623-8 2004 Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates NO-cGMP-mediated smooth muscle relaxation. Cyclic GMP 65-69 phosphodiesterase 5A Homo sapiens 21-25 15229623-9 2004 Inhibition of PDE5 is expected to enhance penile erection by preventing cGMP degradation. Cyclic GMP 72-76 phosphodiesterase 5A Homo sapiens 14-18 15312978-1 2004 The levels of the cGMP in smooth muscle of the gut reflect continued synthesis by soluble guanylate cyclase (GC) and breakdown by phosphodiesterase 5 (PDE5). Cyclic GMP 18-22 phosphodiesterase 5A Homo sapiens 130-149 15475488-2 2004 Nitric oxide-induced smooth muscle relaxation involves activation of soluble guanylate cyclase, with cGMP production, which is then degradated by phosphodiesterase-5 (PDE-5). Cyclic GMP 101-105 phosphodiesterase 5A Homo sapiens 146-165 15475488-2 2004 Nitric oxide-induced smooth muscle relaxation involves activation of soluble guanylate cyclase, with cGMP production, which is then degradated by phosphodiesterase-5 (PDE-5). Cyclic GMP 101-105 phosphodiesterase 5A Homo sapiens 167-172 15881813-1 2004 Newly developed sildenafil citrate (SC), a selective inhibitor of cyclic guanosine monophosphate (c-GMP) specific phosphodiesterase type 5 (PDE 5) in the corpus cavernosum is used for the oral treatment of erectile dysfunction. Cyclic GMP 66-96 phosphodiesterase 5A Homo sapiens 114-138 15881813-1 2004 Newly developed sildenafil citrate (SC), a selective inhibitor of cyclic guanosine monophosphate (c-GMP) specific phosphodiesterase type 5 (PDE 5) in the corpus cavernosum is used for the oral treatment of erectile dysfunction. Cyclic GMP 66-96 phosphodiesterase 5A Homo sapiens 140-145 15881813-1 2004 Newly developed sildenafil citrate (SC), a selective inhibitor of cyclic guanosine monophosphate (c-GMP) specific phosphodiesterase type 5 (PDE 5) in the corpus cavernosum is used for the oral treatment of erectile dysfunction. Cyclic GMP 98-103 phosphodiesterase 5A Homo sapiens 114-138 15881813-1 2004 Newly developed sildenafil citrate (SC), a selective inhibitor of cyclic guanosine monophosphate (c-GMP) specific phosphodiesterase type 5 (PDE 5) in the corpus cavernosum is used for the oral treatment of erectile dysfunction. Cyclic GMP 98-103 phosphodiesterase 5A Homo sapiens 140-145 15312980-1 2004 Phosphodiesterase-5 (PDE5) inhibitors act by competing with the substrate, cGMP, for the catalytic site of the enzyme. Cyclic GMP 75-79 phosphodiesterase 5A Homo sapiens 21-25 15312986-6 2004 Immunocytochemical studies showed that in vitro slice incubations with PDE5 inhibitors increase NO-stimulated cGMP levels mainly in hippocampal varicose fibers. Cyclic GMP 110-114 phosphodiesterase 5A Homo sapiens 71-75 15312978-1 2004 The levels of the cGMP in smooth muscle of the gut reflect continued synthesis by soluble guanylate cyclase (GC) and breakdown by phosphodiesterase 5 (PDE5). Cyclic GMP 18-22 phosphodiesterase 5A Homo sapiens 151-155 15312980-0 2004 Vardenafil: structural basis for higher potency over sildenafil in inhibiting cGMP-specific phosphodiesterase-5 (PDE5). Cyclic GMP 78-82 phosphodiesterase 5A Homo sapiens 92-111 15312980-0 2004 Vardenafil: structural basis for higher potency over sildenafil in inhibiting cGMP-specific phosphodiesterase-5 (PDE5). Cyclic GMP 78-82 phosphodiesterase 5A Homo sapiens 113-117 15312980-1 2004 Phosphodiesterase-5 (PDE5) inhibitors act by competing with the substrate, cGMP, for the catalytic site of the enzyme. Cyclic GMP 75-79 phosphodiesterase 5A Homo sapiens 0-19 15175637-2 2004 Increasing intracellular levels of cGMP reduce the contractile status of VSM; on the contrary, type 5 cGMP-specific phosphodiesterase (PDE5, codified by PDE5A gene) regulates cGMP levels through its clearance. Cyclic GMP 102-106 phosphodiesterase 5A Homo sapiens 135-139 15175637-2 2004 Increasing intracellular levels of cGMP reduce the contractile status of VSM; on the contrary, type 5 cGMP-specific phosphodiesterase (PDE5, codified by PDE5A gene) regulates cGMP levels through its clearance. Cyclic GMP 102-106 phosphodiesterase 5A Homo sapiens 153-158 15571296-4 2004 The cytostatic effect of these compounds increased increasing their concentrations far above their IC50 levels for PDE5, suggesting that these compounds could act by interfering with other molecular events than direct cGMP-PDE inhibition. Cyclic GMP 218-222 phosphodiesterase 5A Homo sapiens 115-119 15295092-2 2004 We hypothesized that changes in PDE5 activity might be involved in the pulmonary postnatal maturation of the nitric oxide (NO)/cGMP pathway. Cyclic GMP 127-131 phosphodiesterase 5A Homo sapiens 32-36 15295092-9 2004 Both total and PDE5-dependent cGMP hydrolytic activity and PDE5 protein expression increased with postnatal age. Cyclic GMP 30-34 phosphodiesterase 5A Homo sapiens 15-19 15357833-4 2004 Here we report that long-term application of hypergravity (up to 5 g for 24 h) stimulated cGMP efflux in cultured melanocytes and in non-metastatic melanoma cells in the presence of 0.1 mM 3-isobutyl-1-methylxanthine (IBMX), a non-selective phosphodiesterase (PDE) inhibitor. Cyclic GMP 90-94 phosphodiesterase 5A Homo sapiens 260-263 15357833-6 2004 Hypergravity also stimulated cGMP transport in the presence of 1 microM trequinsin, an inhibitor of cGMP-binding PDE (PDE5) and of transport by multidrug resistance proteins MRP4/5, whereas 50 microM trequinsin partially inhibited cGMP transport. Cyclic GMP 29-33 phosphodiesterase 5A Homo sapiens 113-116 15357833-6 2004 Hypergravity also stimulated cGMP transport in the presence of 1 microM trequinsin, an inhibitor of cGMP-binding PDE (PDE5) and of transport by multidrug resistance proteins MRP4/5, whereas 50 microM trequinsin partially inhibited cGMP transport. Cyclic GMP 29-33 phosphodiesterase 5A Homo sapiens 118-122 15357833-6 2004 Hypergravity also stimulated cGMP transport in the presence of 1 microM trequinsin, an inhibitor of cGMP-binding PDE (PDE5) and of transport by multidrug resistance proteins MRP4/5, whereas 50 microM trequinsin partially inhibited cGMP transport. Cyclic GMP 100-104 phosphodiesterase 5A Homo sapiens 113-116 15357833-6 2004 Hypergravity also stimulated cGMP transport in the presence of 1 microM trequinsin, an inhibitor of cGMP-binding PDE (PDE5) and of transport by multidrug resistance proteins MRP4/5, whereas 50 microM trequinsin partially inhibited cGMP transport. Cyclic GMP 100-104 phosphodiesterase 5A Homo sapiens 113-116 16422967-8 2004 RESULTS: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 35-39 15333581-6 2004 The NO donor diethylamine NONOate (DEANO), the PKG activator 8-pCPT-cGMP, and the PDE-5 inhibitor sildenafil, cause dose-dependent clitoral relaxation that is inhibited by antagonists of PKG (Rp-8-Br-cGMPS) or BK(Ca) channels (iberiotoxin). Cyclic GMP 200-205 phosphodiesterase 5A Homo sapiens 82-87 15240816-3 2004 Both characteristics have been attributed to PDE5 activation caused by cGMP binding to its regulatory GAF domain. Cyclic GMP 71-75 phosphodiesterase 5A Homo sapiens 45-49 15240816-5 2004 Here, we report reconstitution of all features of the NO-induced cGMP response in human embryonic kidney cells by coexpressing NO-sensitive GC and PDE5. Cyclic GMP 65-69 phosphodiesterase 5A Homo sapiens 147-151 15240816-6 2004 The spike-like cGMP response was blunted when PDE5 phosphorylation was enhanced by additional overexpression of cGMP-dependent protein kinase. Cyclic GMP 15-19 phosphodiesterase 5A Homo sapiens 46-50 15240816-7 2004 Analysis of PDE5 activation in vitro revealed a discrepancy between the cGMP concentrations required for activation (micromolar) and reversal of activation (nanomolar), indicating the conversion of a low-affinity state to a high-affinity state upon binding of cGMP. Cyclic GMP 72-76 phosphodiesterase 5A Homo sapiens 12-16 15240816-7 2004 Analysis of PDE5 activation in vitro revealed a discrepancy between the cGMP concentrations required for activation (micromolar) and reversal of activation (nanomolar), indicating the conversion of a low-affinity state to a high-affinity state upon binding of cGMP. Cyclic GMP 260-264 phosphodiesterase 5A Homo sapiens 12-16 15240816-8 2004 Phosphorylation even increased the high apparent affinity enabling PDE5 activation to persist at extremely low cGMP concentrations. Cyclic GMP 111-115 phosphodiesterase 5A Homo sapiens 67-71 15240816-9 2004 Our data suggest that the spike-like shape and the desensitization of the cGMP response are potentially inherent to every GC- and PDE5-expressing cell. Cyclic GMP 74-78 phosphodiesterase 5A Homo sapiens 130-134 15045518-14 2004 The exact mechanism by which such an interaction occurs is not clear, but it may involve altered activity of the cGMP-inhibited PDE3 brought about by a change in the intracellular levels of cGMP by the inhibition of PDE5. Cyclic GMP 113-117 phosphodiesterase 5A Homo sapiens 216-220 15045518-14 2004 The exact mechanism by which such an interaction occurs is not clear, but it may involve altered activity of the cGMP-inhibited PDE3 brought about by a change in the intracellular levels of cGMP by the inhibition of PDE5. Cyclic GMP 190-194 phosphodiesterase 5A Homo sapiens 216-220 16422967-8 2004 RESULTS: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. Cyclic GMP 89-93 phosphodiesterase 5A Homo sapiens 223-227 16422967-8 2004 RESULTS: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. Cyclic GMP 188-192 phosphodiesterase 5A Homo sapiens 35-39 16422967-8 2004 RESULTS: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. Cyclic GMP 188-192 phosphodiesterase 5A Homo sapiens 223-227 16422967-9 2004 PDE5 inhibitors, which vary as to biochemical potency, selectivity and pharmacokinetics, lead to cGMP elevation and relaxation facilitation of penile corpus cavernosum smooth muscle cells following sexual stimulation. Cyclic GMP 97-101 phosphodiesterase 5A Homo sapiens 0-4 15213306-0 2004 Binding of tritiated sildenafil, tadalafil, or vardenafil to the phosphodiesterase-5 catalytic site displays potency, specificity, heterogeneity, and cGMP stimulation. Cyclic GMP 150-154 phosphodiesterase 5A Homo sapiens 65-84 15223851-3 2004 Both of these Pde-5 inhibitors have vasodilating properties and effects on blood pressure (BP), and like nitrates, they work through the nitric oxide cyclic guanosine monophosphate pathway. Cyclic GMP 150-180 phosphodiesterase 5A Homo sapiens 14-19 15213306-1 2004 Sildenafil, tadalafil, and vardenafil each competitively inhibit cGMP hydrolysis by phosphodiesterase-5 (PDE5), thereby fostering cGMP accumulation and relaxation of vascular smooth muscle. Cyclic GMP 65-69 phosphodiesterase 5A Homo sapiens 84-103 15213306-1 2004 Sildenafil, tadalafil, and vardenafil each competitively inhibit cGMP hydrolysis by phosphodiesterase-5 (PDE5), thereby fostering cGMP accumulation and relaxation of vascular smooth muscle. Cyclic GMP 65-69 phosphodiesterase 5A Homo sapiens 105-109 15213306-1 2004 Sildenafil, tadalafil, and vardenafil each competitively inhibit cGMP hydrolysis by phosphodiesterase-5 (PDE5), thereby fostering cGMP accumulation and relaxation of vascular smooth muscle. Cyclic GMP 130-134 phosphodiesterase 5A Homo sapiens 84-103 15213306-1 2004 Sildenafil, tadalafil, and vardenafil each competitively inhibit cGMP hydrolysis by phosphodiesterase-5 (PDE5), thereby fostering cGMP accumulation and relaxation of vascular smooth muscle. Cyclic GMP 130-134 phosphodiesterase 5A Homo sapiens 105-109 15213306-10 2004 cGMP addition increased binding affinity of [(3)H]tadalafil or [(3)H]vardenafil, an effect presumably mediated by cGMP binding to PDE5 allosteric sites, implying that either inhibitor potentiates its own binding to PDE5 in intact cells by elevating cGMP. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 130-134 15213306-10 2004 cGMP addition increased binding affinity of [(3)H]tadalafil or [(3)H]vardenafil, an effect presumably mediated by cGMP binding to PDE5 allosteric sites, implying that either inhibitor potentiates its own binding to PDE5 in intact cells by elevating cGMP. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 215-219 15213306-10 2004 cGMP addition increased binding affinity of [(3)H]tadalafil or [(3)H]vardenafil, an effect presumably mediated by cGMP binding to PDE5 allosteric sites, implying that either inhibitor potentiates its own binding to PDE5 in intact cells by elevating cGMP. Cyclic GMP 114-118 phosphodiesterase 5A Homo sapiens 130-134 15213306-10 2004 cGMP addition increased binding affinity of [(3)H]tadalafil or [(3)H]vardenafil, an effect presumably mediated by cGMP binding to PDE5 allosteric sites, implying that either inhibitor potentiates its own binding to PDE5 in intact cells by elevating cGMP. Cyclic GMP 114-118 phosphodiesterase 5A Homo sapiens 130-134 15093609-0 2004 The cGMP-binding, cGMP-specific phosphodiesterase (PDE5): intestinal cell expression, regulation and role in fluid secretion. Cyclic GMP 4-8 phosphodiesterase 5A Homo sapiens 51-55 15093609-0 2004 The cGMP-binding, cGMP-specific phosphodiesterase (PDE5): intestinal cell expression, regulation and role in fluid secretion. Cyclic GMP 18-22 phosphodiesterase 5A Homo sapiens 51-55 15093609-1 2004 The expression and regulation of the cGMP-binding, cGMP-specific phosphodiesterase, PDE5, was studied in intestinal cells. Cyclic GMP 37-41 phosphodiesterase 5A Homo sapiens 84-88 15093609-2 2004 Both PDE5A1 and PDE5A2 splice forms were cloned from the cDNA prepared from human colonic T84 cells, and PDE5 activity was dependent on increases in intracellular cGMP levels which correlated with increased phosphorylation of the enzyme. Cyclic GMP 163-167 phosphodiesterase 5A Homo sapiens 5-9 15224127-5 2004 The catalytic site of PDE5 normally degrades cGMP, and PDE5 inhibitors such as sildenafil potentiate endogenous increases in cGMP by inhibiting its breakdown at the catalytic site. Cyclic GMP 45-49 phosphodiesterase 5A Homo sapiens 22-26 15224136-1 2004 Phosphodiesterase 5 (PDE5) inhibitors prevent the normal hydrolysis of cGMP. Cyclic GMP 71-75 phosphodiesterase 5A Homo sapiens 0-19 15224136-1 2004 Phosphodiesterase 5 (PDE5) inhibitors prevent the normal hydrolysis of cGMP. Cyclic GMP 71-75 phosphodiesterase 5A Homo sapiens 21-25 15224136-2 2004 As the resulting cGMP accumulation facilitates penile smooth muscle relaxation, PDE5 inhibitors can partially reverse deficiencies in the nitric oxide (NO)/cGMP pathway to treat erectile dysfunction (ED). Cyclic GMP 17-21 phosphodiesterase 5A Homo sapiens 80-84 15224136-2 2004 As the resulting cGMP accumulation facilitates penile smooth muscle relaxation, PDE5 inhibitors can partially reverse deficiencies in the nitric oxide (NO)/cGMP pathway to treat erectile dysfunction (ED). Cyclic GMP 156-160 phosphodiesterase 5A Homo sapiens 80-84 15224136-5 2004 Decreased expression or activity of neuronal or endothelial NO synthase (NOS), impaired NO release, or NO destruction will preclude sufficient cGMP formation to permit PDE5 inhibitor efficacy. Cyclic GMP 143-147 phosphodiesterase 5A Homo sapiens 168-172 15224127-5 2004 The catalytic site of PDE5 normally degrades cGMP, and PDE5 inhibitors such as sildenafil potentiate endogenous increases in cGMP by inhibiting its breakdown at the catalytic site. Cyclic GMP 125-129 phosphodiesterase 5A Homo sapiens 22-26 15224127-5 2004 The catalytic site of PDE5 normally degrades cGMP, and PDE5 inhibitors such as sildenafil potentiate endogenous increases in cGMP by inhibiting its breakdown at the catalytic site. Cyclic GMP 125-129 phosphodiesterase 5A Homo sapiens 55-59 15224127-6 2004 Phosphorylation of PDE5 increases its enzymatic activity as well as the affinity of its allosteric (noncatalytic/GAF domains) sites for cGMP. Cyclic GMP 136-140 phosphodiesterase 5A Homo sapiens 19-23 15224127-8 2004 Thus phosphorylation of PDE5 and binding of cGMP to the noncatalytic sites mediate negative feedback regulation of the cGMP pathway. Cyclic GMP 119-123 phosphodiesterase 5A Homo sapiens 24-28 15224132-2 2004 PDE4 and PDE5 selectively hydrolyze cAMP and cGMP, respectively. Cyclic GMP 45-49 phosphodiesterase 5A Homo sapiens 9-13 15224133-5 2004 The PDE6 catalytic subunits resemble PDE5 in amino-acid sequence as well as in three-dimensional structure of the catalytic dimer; preference for cGMP over cyclic adenosine monophosphate (cAMP) as a substrate; and the ability to bind cGMP at the regulatory GAF domains. Cyclic GMP 146-150 phosphodiesterase 5A Homo sapiens 37-41 15088685-2 2004 The present study was aimed to investigate the NO-cGMP-PDE5 pathway in nociceptive conditions in the experimental animals. Cyclic GMP 50-54 phosphodiesterase 5A Homo sapiens 55-59 15041473-6 2004 In contrast, inhibition of PDE5 increased the cGMP level, but without significant influence on aggregation, alphaIIbbeta3 activation, secretion or procoagulant activity. Cyclic GMP 46-50 phosphodiesterase 5A Homo sapiens 27-31 15041473-7 2004 Nitroprusside (nitric oxide) potentiated the effect of PDE5 inhibition in elevating cGMP. Cyclic GMP 84-88 phosphodiesterase 5A Homo sapiens 55-59 15066950-8 2004 BAY 41-2272 not only sensitized NO-sensitive GC toward activation by NO but also, with comparable potency, inhibited cGMP degradation by PDE5. Cyclic GMP 117-121 phosphodiesterase 5A Homo sapiens 137-141 15080987-3 2004 Docking model of (PDE5: 12d) complex shows that the PDE5-bound conformation of 12d matches completely with that of sildenafil, while 12d is partially overlapped with cGMP with ethyl phosphonate group of 12d superimposed onto the cyclic phosphate group of cGMP. Cyclic GMP 166-170 phosphodiesterase 5A Homo sapiens 18-22 15080987-3 2004 Docking model of (PDE5: 12d) complex shows that the PDE5-bound conformation of 12d matches completely with that of sildenafil, while 12d is partially overlapped with cGMP with ethyl phosphonate group of 12d superimposed onto the cyclic phosphate group of cGMP. Cyclic GMP 166-170 phosphodiesterase 5A Homo sapiens 52-56 15080987-3 2004 Docking model of (PDE5: 12d) complex shows that the PDE5-bound conformation of 12d matches completely with that of sildenafil, while 12d is partially overlapped with cGMP with ethyl phosphonate group of 12d superimposed onto the cyclic phosphate group of cGMP. Cyclic GMP 255-259 phosphodiesterase 5A Homo sapiens 18-22 15080987-3 2004 Docking model of (PDE5: 12d) complex shows that the PDE5-bound conformation of 12d matches completely with that of sildenafil, while 12d is partially overlapped with cGMP with ethyl phosphonate group of 12d superimposed onto the cyclic phosphate group of cGMP. Cyclic GMP 255-259 phosphodiesterase 5A Homo sapiens 52-56 15066950-4 2004 However, YC-1 has also been shown to inhibit the major cGMP-degrading enzyme phosphodiesterase type 5 (PDE5). Cyclic GMP 55-59 phosphodiesterase 5A Homo sapiens 77-101 15066950-4 2004 However, YC-1 has also been shown to inhibit the major cGMP-degrading enzyme phosphodiesterase type 5 (PDE5). Cyclic GMP 55-59 phosphodiesterase 5A Homo sapiens 103-107 14551572-1 2003 Phosphodiesterase type 5 (PDE 5) is the major cGMP hydrolyzing enzyme in penile corpus cavernosum and is an important regulator of nitric oxide-mediated smooth muscle relaxation. Cyclic GMP 46-50 phosphodiesterase 5A Homo sapiens 0-24 14652001-8 2003 This could explain the poor clinical response to PDE5 inhibitors of diabetic men with ED and suggests that a pharmacological approach that combines enhancement of NO/cGMP and EDHF pathways could be necessary to treat ED in many diabetic men. Cyclic GMP 166-170 phosphodiesterase 5A Homo sapiens 49-53 14622499-6 2003 This article focuses on the basic biochemistry of cyclic guanosine monophosphate signaling and the pharmacokinetic parameters that describe characteristics of drug action of these PDE-5 inhibitors in facilitating smooth muscle relaxation, leading to improved penile erectile response or causing side effects. Cyclic GMP 50-80 phosphodiesterase 5A Homo sapiens 180-185 14609619-4 2003 Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates nitric oxide-cGMP-mediated smooth muscle relaxation. Cyclic GMP 39-43 phosphodiesterase 5A Homo sapiens 0-19 14609619-4 2003 Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates nitric oxide-cGMP-mediated smooth muscle relaxation. Cyclic GMP 39-43 phosphodiesterase 5A Homo sapiens 21-25 14609619-4 2003 Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates nitric oxide-cGMP-mediated smooth muscle relaxation. Cyclic GMP 75-79 phosphodiesterase 5A Homo sapiens 0-19 14609619-4 2003 Phosphodiesterase 5 (PDE5) inactivates cGMP, which terminates nitric oxide-cGMP-mediated smooth muscle relaxation. Cyclic GMP 75-79 phosphodiesterase 5A Homo sapiens 21-25 14609619-5 2003 Inhibition of PDE5 is expected to enhance penile erection by preventing cGMP degradation. Cyclic GMP 72-76 phosphodiesterase 5A Homo sapiens 14-18 14551572-1 2003 Phosphodiesterase type 5 (PDE 5) is the major cGMP hydrolyzing enzyme in penile corpus cavernosum and is an important regulator of nitric oxide-mediated smooth muscle relaxation. Cyclic GMP 46-50 phosphodiesterase 5A Homo sapiens 26-31 12933699-3 2003 For example, PDE5 as a major cGMP-hydrolyzing PDE effectively controls the development of smooth muscle relaxation. Cyclic GMP 29-33 phosphodiesterase 5A Homo sapiens 13-17 14569381-1 2003 Erectile dysfunction (ED) management in the following 3-5 years will be dominated by substances targeting the L-arginine-NO-guanylate cyclase-cGMP-PDE-5 pathway, resulting in an intracellular elevation of the cGMP concentrations. Cyclic GMP 142-146 phosphodiesterase 5A Homo sapiens 147-152 14569381-1 2003 Erectile dysfunction (ED) management in the following 3-5 years will be dominated by substances targeting the L-arginine-NO-guanylate cyclase-cGMP-PDE-5 pathway, resulting in an intracellular elevation of the cGMP concentrations. Cyclic GMP 209-213 phosphodiesterase 5A Homo sapiens 147-152 12970227-2 2003 In other forms of pulmonary vascular disease with increased PVR, an elevated activity of a phosphodiesterase type 5 (PDE-5), responsible for the degradation of cyclic guanidine monophosphate (cGMP), the second messenger of endothelially produced NO, has been demonstrated. Cyclic GMP 192-196 phosphodiesterase 5A Homo sapiens 91-115 12970227-2 2003 In other forms of pulmonary vascular disease with increased PVR, an elevated activity of a phosphodiesterase type 5 (PDE-5), responsible for the degradation of cyclic guanidine monophosphate (cGMP), the second messenger of endothelially produced NO, has been demonstrated. Cyclic GMP 192-196 phosphodiesterase 5A Homo sapiens 117-122 12970227-8 2003 The increase in cGMP in response to NO was potentiated (2- to 2.4-fold) by PDE-5 inhibition. Cyclic GMP 16-20 phosphodiesterase 5A Homo sapiens 75-80 12955149-3 2003 Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. Cyclic GMP 29-33 phosphodiesterase 5A Homo sapiens 43-47 12955149-3 2003 Of the 12 PDE gene families, cGMP-specific PDE5 carries out the principal cGMP-hydrolysing activity in human corpus cavernosum tissue. Cyclic GMP 74-78 phosphodiesterase 5A Homo sapiens 43-47 14626653-3 2003 Inhibition of PDE5 blocks the hydrolysis of cyclic guanosine monophosphate (GMPc) and results in increased arterial blood flow leading to enlargement of the corpus cavernosum and resulting in erection. Cyclic GMP 44-74 phosphodiesterase 5A Homo sapiens 14-18 12933699-6 2003 A recently shown direct activation of PDE5 by cGMP binding to the GAF A domain suggests that this regulatory site might be a target for new drug development. Cyclic GMP 46-50 phosphodiesterase 5A Homo sapiens 38-42 12933699-8 2003 Together, PDE5 and PDE1A lower cGMP sufficiently to allow contraction. Cyclic GMP 31-35 phosphodiesterase 5A Homo sapiens 10-14 12825143-15 2003 Sildenafil acts as a selective inhibitor of cyclic guanosine monophosphate-(cGMP-)specific phosphodiesterase type 5 (PDE 5), resulting in smooth muscle relaxation, vasodilation, and enhanced penile erection. Cyclic GMP 44-74 phosphodiesterase 5A Homo sapiens 117-122 12934045-5 2003 PDE5 inhibitors such as sildenafil promote the cGMP pathway, while alprostadil affects the cAMP pathway. Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 0-4 12881475-4 2003 Sensitization and desensitization of NO/cGMP signaling have been reported to occur on the level of NO-sensitive GC; in the present study, an alternative mechanism is introduced explaining the adaptation of the NO-induced cGMP response by a long-term activation of the cGMP-degrading phosphodiesterase 5 (PDE5). Cyclic GMP 40-44 phosphodiesterase 5A Homo sapiens 304-308 12881475-4 2003 Sensitization and desensitization of NO/cGMP signaling have been reported to occur on the level of NO-sensitive GC; in the present study, an alternative mechanism is introduced explaining the adaptation of the NO-induced cGMP response by a long-term activation of the cGMP-degrading phosphodiesterase 5 (PDE5). Cyclic GMP 221-225 phosphodiesterase 5A Homo sapiens 304-308 12881475-4 2003 Sensitization and desensitization of NO/cGMP signaling have been reported to occur on the level of NO-sensitive GC; in the present study, an alternative mechanism is introduced explaining the adaptation of the NO-induced cGMP response by a long-term activation of the cGMP-degrading phosphodiesterase 5 (PDE5). Cyclic GMP 221-225 phosphodiesterase 5A Homo sapiens 304-308 12825143-15 2003 Sildenafil acts as a selective inhibitor of cyclic guanosine monophosphate-(cGMP-)specific phosphodiesterase type 5 (PDE 5), resulting in smooth muscle relaxation, vasodilation, and enhanced penile erection. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 117-122 12614192-2 2003 The scientific basis of this treatment of ED includes relaxation of the corpus cavernosum smooth muscle tissue by inhibition of PDE5 that breaks down cGMP, the key pathway for the production of erectile function in humans. Cyclic GMP 150-154 phosphodiesterase 5A Homo sapiens 128-132 12761347-0 2003 [3H]sildenafil binding to phosphodiesterase-5 is specific, kinetically heterogeneous, and stimulated by cGMP. Cyclic GMP 104-108 phosphodiesterase 5A Homo sapiens 26-45 12761347-8 2003 Results suggest that these effects occur via cGMP binding to the allosteric cGMP binding sites of PDE5. Cyclic GMP 45-49 phosphodiesterase 5A Homo sapiens 98-102 12761347-8 2003 Results suggest that these effects occur via cGMP binding to the allosteric cGMP binding sites of PDE5. Cyclic GMP 76-80 phosphodiesterase 5A Homo sapiens 98-102 12761347-9 2003 Results imply that by inhibiting PDE5 and thereby increasing cGMP, sildenafil accentuates its own binding affinity for PDE5, which further elevates cGMP. Cyclic GMP 61-65 phosphodiesterase 5A Homo sapiens 119-123 12761347-9 2003 Results imply that by inhibiting PDE5 and thereby increasing cGMP, sildenafil accentuates its own binding affinity for PDE5, which further elevates cGMP. Cyclic GMP 148-152 phosphodiesterase 5A Homo sapiens 33-37 12761347-9 2003 Results imply that by inhibiting PDE5 and thereby increasing cGMP, sildenafil accentuates its own binding affinity for PDE5, which further elevates cGMP. Cyclic GMP 148-152 phosphodiesterase 5A Homo sapiens 119-123 12761347-10 2003 The data also indicate that after physiological elevation, cGMP may directly stimulate the catalytic site by binding to the allosteric cGMP-binding sites of PDE5, thus causing negative feedback on this pathway. Cyclic GMP 59-63 phosphodiesterase 5A Homo sapiens 157-161 12761347-10 2003 The data also indicate that after physiological elevation, cGMP may directly stimulate the catalytic site by binding to the allosteric cGMP-binding sites of PDE5, thus causing negative feedback on this pathway. Cyclic GMP 135-139 phosphodiesterase 5A Homo sapiens 157-161 12694895-1 2003 Sildenafil (Viagra) is a selective inhibitor of the cyclic guanosine monophosphate (cGMP) specific phosphodiesterase 5 (PDE5) used for the oral treatment of male erectile dysfunction due to vasodilation. Cyclic GMP 52-82 phosphodiesterase 5A Homo sapiens 99-118 12694895-1 2003 Sildenafil (Viagra) is a selective inhibitor of the cyclic guanosine monophosphate (cGMP) specific phosphodiesterase 5 (PDE5) used for the oral treatment of male erectile dysfunction due to vasodilation. Cyclic GMP 52-82 phosphodiesterase 5A Homo sapiens 120-124 12694895-1 2003 Sildenafil (Viagra) is a selective inhibitor of the cyclic guanosine monophosphate (cGMP) specific phosphodiesterase 5 (PDE5) used for the oral treatment of male erectile dysfunction due to vasodilation. Cyclic GMP 84-88 phosphodiesterase 5A Homo sapiens 99-118 12694895-1 2003 Sildenafil (Viagra) is a selective inhibitor of the cyclic guanosine monophosphate (cGMP) specific phosphodiesterase 5 (PDE5) used for the oral treatment of male erectile dysfunction due to vasodilation. Cyclic GMP 84-88 phosphodiesterase 5A Homo sapiens 120-124 12604588-0 2003 Direct activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling. Cyclic GMP 29-33 phosphodiesterase 5A Homo sapiens 21-25 12604588-0 2003 Direct activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling. Cyclic GMP 63-67 phosphodiesterase 5A Homo sapiens 21-25 12604588-2 2003 Recently, we showed that within the NO-induced cGMP response in human platelets, activation and phosphorylation of phosphodiesterase type 5 (PDE5) occurred. Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 115-139 12604588-2 2003 Recently, we showed that within the NO-induced cGMP response in human platelets, activation and phosphorylation of phosphodiesterase type 5 (PDE5) occurred. Cyclic GMP 47-51 phosphodiesterase 5A Homo sapiens 141-145 12604588-4 2003 However, we demonstrate that cGMP can directly activate PDE5 without phosphorylation in platelet cytosol, most likely via binding to the regulatory GAF domains. Cyclic GMP 29-33 phosphodiesterase 5A Homo sapiens 56-60 12604588-8 2003 Finally, the long-term desensitization of the cGMP response induced by a low NO concentration reveals the physiological relevance of the PDE5 activation within NO/cGMP signaling. Cyclic GMP 46-50 phosphodiesterase 5A Homo sapiens 137-141 12604588-8 2003 Finally, the long-term desensitization of the cGMP response induced by a low NO concentration reveals the physiological relevance of the PDE5 activation within NO/cGMP signaling. Cyclic GMP 163-167 phosphodiesterase 5A Homo sapiens 137-141 12604588-9 2003 In sum, we suggest NO-induced activation and phosphorylation of PDE5 as the mechanism for a long-lasting negative feedback loop shaping the cGMP response in human platelets in order to adapt to the amount of NO available. Cyclic GMP 140-144 phosphodiesterase 5A Homo sapiens 64-68 12646997-8 2003 CONCLUSION: Icariin is a cGMP-specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED. Cyclic GMP 25-29 phosphodiesterase 5A Homo sapiens 39-43 12789393-1 2003 Inhibition of cGMP-specific phosphodiesterase type 5 (PDE5) has been shown to improve penile erection in patients with erectile dysfunction. Cyclic GMP 14-18 phosphodiesterase 5A Homo sapiens 54-58 12789394-2 2003 Vardenafil is a type 5 phosphodiesterase (PDE5) inhibitor that potentiates the nitric oxide (NO)/cGMP pathway facilitating penile smooth muscle relaxation and improving penile erection in men. Cyclic GMP 97-101 phosphodiesterase 5A Homo sapiens 42-46 12646997-0 2003 Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Cyclic GMP 22-26 phosphodiesterase 5A Homo sapiens 36-40 12554648-0 2003 PDE5 is converted to an activated state upon cGMP binding to the GAF A domain. Cyclic GMP 45-49 phosphodiesterase 5A Homo sapiens 0-4 12554648-1 2003 cGMP-specific, cGMP-binding phosphodiesterase (PDE5) regulates such physiological processes as smooth muscle relaxation and neuronal survival. Cyclic GMP 0-4 phosphodiesterase 5A Homo sapiens 47-51 12554648-1 2003 cGMP-specific, cGMP-binding phosphodiesterase (PDE5) regulates such physiological processes as smooth muscle relaxation and neuronal survival. Cyclic GMP 15-19 phosphodiesterase 5A Homo sapiens 47-51 12554648-3 2003 Here we show that recombinant PDE5 is activated directly upon cGMP binding to the GAF A domain, and this effect does not require PDE5 phosphorylation. Cyclic GMP 62-66 phosphodiesterase 5A Homo sapiens 30-34 12554648-4 2003 PDE5 exhibited time- and concentration-dependent reversible activation in response to cGMP, with the highest activation (9- to 11-fold) observed at low substrate concentrations (0.1 micro M cGMP). Cyclic GMP 86-90 phosphodiesterase 5A Homo sapiens 0-4 12554648-4 2003 PDE5 exhibited time- and concentration-dependent reversible activation in response to cGMP, with the highest activation (9- to 11-fold) observed at low substrate concentrations (0.1 micro M cGMP). Cyclic GMP 190-194 phosphodiesterase 5A Homo sapiens 0-4 12554648-5 2003 A monoclonal antibody directed against GAF A blocked cGMP binding, prevented PDE5 activation and decreased basal activity, revealing that PDE5 in its non-activated state has low intrinsic catalytic activity. Cyclic GMP 53-57 phosphodiesterase 5A Homo sapiens 138-142 12554648-7 2003 The stimulatory effect of cGMP binding on the catalytic activity of PDE5 suggests that this mechanism of enzyme activation may be common among other GAF domain-containing proteins. Cyclic GMP 26-30 phosphodiesterase 5A Homo sapiens 68-72 12477710-3 2003 We examined whether sildenafil (Viagra), a selective inhibitor of cGMP-hydrolysing phosphodiesterase 5 (PDE5), which acts exclusively by increasing cGMP, can induce migraine and dilatation of cerebral arteries. Cyclic GMP 66-70 phosphodiesterase 5A Homo sapiens 104-108 12477710-3 2003 We examined whether sildenafil (Viagra), a selective inhibitor of cGMP-hydrolysing phosphodiesterase 5 (PDE5), which acts exclusively by increasing cGMP, can induce migraine and dilatation of cerebral arteries. Cyclic GMP 148-152 phosphodiesterase 5A Homo sapiens 104-108 12841917-1 2003 Sildenafil citrate (Viagra) is a potent orally active cGMP-specific phosphodiesterase type 5 (PDE5) inhibitor that is effective as a peripheral conditioner in the treatment of male erectile dysfunction (ED) of organic, psychogenic or mixed aetiology. Cyclic GMP 54-58 phosphodiesterase 5A Homo sapiens 94-98 12414329-5 2002 Therefore, in men with ED, elevation of cGMP in corpus cavernosal tissue via selective inhibition of cGMP-specific PDE5 is a means of improving erectile function at minimal risk of adverse events. Cyclic GMP 40-44 phosphodiesterase 5A Homo sapiens 115-119 12414329-5 2002 Therefore, in men with ED, elevation of cGMP in corpus cavernosal tissue via selective inhibition of cGMP-specific PDE5 is a means of improving erectile function at minimal risk of adverse events. Cyclic GMP 101-105 phosphodiesterase 5A Homo sapiens 115-119 12359732-0 2002 Phosphorylation of isolated human phosphodiesterase-5 regulatory domain induces an apparent conformational change and increases cGMP binding affinity. Cyclic GMP 128-132 phosphodiesterase 5A Homo sapiens 34-53 12359732-1 2002 Substrate binding to the phosphodiesterase-5 (PDE5) catalytic site increases cGMP binding to the regulatory domain (R domain). Cyclic GMP 77-81 phosphodiesterase 5A Homo sapiens 25-44 12359732-1 2002 Substrate binding to the phosphodiesterase-5 (PDE5) catalytic site increases cGMP binding to the regulatory domain (R domain). Cyclic GMP 77-81 phosphodiesterase 5A Homo sapiens 46-50 12359732-2 2002 The latter promotes PDE5 phosphorylation by cyclic nucleotide-dependent protein kinases, which activates catalysis, enhances allosteric cGMP binding, and causes PDE5A1 to apparently elongate. Cyclic GMP 136-140 phosphodiesterase 5A Homo sapiens 20-24 12359732-4 2002 The rate, cGMP dependence, and stoichiometry of phosphorylation of the PDE5 R domain by the catalytic subunit of cAMP-dependent protein kinase are comparable with that of the holoenzyme. Cyclic GMP 10-14 phosphodiesterase 5A Homo sapiens 71-75 12359732-8 2002 Thus, cGMP-directed regulation of PDE5 phosphorylation and the resulting increase in cGMP binding affinity occur largely within the R domain. Cyclic GMP 6-10 phosphodiesterase 5A Homo sapiens 34-38 12359732-8 2002 Thus, cGMP-directed regulation of PDE5 phosphorylation and the resulting increase in cGMP binding affinity occur largely within the R domain. Cyclic GMP 85-89 phosphodiesterase 5A Homo sapiens 34-38 12510841-5 2002 This suggests that DA-8159 is a potent, highly selective, competitive inhibitor of PDE 5-catalyzed cGMP hydrolysis. Cyclic GMP 99-103 phosphodiesterase 5A Homo sapiens 83-88 12510841-6 2002 The rates of cGMP hydrolysis catalyzed by human platelets-derived PDE 5 as a function of the cGMP concentration (5-100 nM) and two-fixed DA-8159 concentration (11.3 and 18.8 nM) were investigated in order to characterize the mode of PDE 5 inhibition by DA-8159. Cyclic GMP 13-17 phosphodiesterase 5A Homo sapiens 66-71 12510841-6 2002 The rates of cGMP hydrolysis catalyzed by human platelets-derived PDE 5 as a function of the cGMP concentration (5-100 nM) and two-fixed DA-8159 concentration (11.3 and 18.8 nM) were investigated in order to characterize the mode of PDE 5 inhibition by DA-8159. Cyclic GMP 93-97 phosphodiesterase 5A Homo sapiens 66-71 12510841-11 2002 In conclusion, DA-8159 is a selective inhibitor of PDE 5-catalyzed cGMP hydrolysis and the enhancement of a penile erection by DA-8159 is mediated by the relaxation of the cavernosal smooth muscle by the NO-stimulated cGMP accumulation. Cyclic GMP 67-71 phosphodiesterase 5A Homo sapiens 51-56 12510841-11 2002 In conclusion, DA-8159 is a selective inhibitor of PDE 5-catalyzed cGMP hydrolysis and the enhancement of a penile erection by DA-8159 is mediated by the relaxation of the cavernosal smooth muscle by the NO-stimulated cGMP accumulation. Cyclic GMP 218-222 phosphodiesterase 5A Homo sapiens 51-56 15570464-0 2002 Use of cGMP PDE5 inhibitors in the treatment of neuropathy: a review of the patent literature. Cyclic GMP 7-11 phosphodiesterase 5A Homo sapiens 12-16 15570464-5 2002 It also explores the possible hypotheses that may help to explain the mechanism(s) by which cGMP PDE5 inhibitors could have potential benefits in neuropathy. Cyclic GMP 92-96 phosphodiesterase 5A Homo sapiens 97-101 11930017-4 2002 Two GAF (for cGMP binding and stimulated PDEs, Anabaena adenylyl cyclases, and Escherichia coli FhlA) domains, similar to those contained in many signaling molecules including mammalian PDE2, PDE5, PDE6, PDE10, and PDE11, were located N-terminal to a consensus PDE catalytic domain. Cyclic GMP 13-17 phosphodiesterase 5A Homo sapiens 192-196 11958981-1 2002 2-aryl-substituted imidazo[5,1-f][1,2,4]triazin-4(3H)-ones represent a new class of potent cGMP-PDE 5 inhibitors that prove to be superior to other purine-isosteric inhibitors. Cyclic GMP 91-95 phosphodiesterase 5A Homo sapiens 96-101