PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 25773497-3 2015 The discovery of hydroxy-carboxylic acid receptor 2 (HCA2) as a high affinity receptor for niacin has opened avenues to investigate the mechanism of action of niacin, and to potentially discover agonists which maintain the antilipolytic effects of niacin accessed by a decrease in circulating non-esterified fatty acids (NEFA) and thereby perhaps the lipid/lipoprotein effects, but avoid the flushing effects. Niacin 91-97 hydroxycarboxylic acid receptor 2 Homo sapiens 17-51 25773497-3 2015 The discovery of hydroxy-carboxylic acid receptor 2 (HCA2) as a high affinity receptor for niacin has opened avenues to investigate the mechanism of action of niacin, and to potentially discover agonists which maintain the antilipolytic effects of niacin accessed by a decrease in circulating non-esterified fatty acids (NEFA) and thereby perhaps the lipid/lipoprotein effects, but avoid the flushing effects. Niacin 91-97 hydroxycarboxylic acid receptor 2 Homo sapiens 53-57 25773497-3 2015 The discovery of hydroxy-carboxylic acid receptor 2 (HCA2) as a high affinity receptor for niacin has opened avenues to investigate the mechanism of action of niacin, and to potentially discover agonists which maintain the antilipolytic effects of niacin accessed by a decrease in circulating non-esterified fatty acids (NEFA) and thereby perhaps the lipid/lipoprotein effects, but avoid the flushing effects. Niacin 159-165 hydroxycarboxylic acid receptor 2 Homo sapiens 17-51 25773497-3 2015 The discovery of hydroxy-carboxylic acid receptor 2 (HCA2) as a high affinity receptor for niacin has opened avenues to investigate the mechanism of action of niacin, and to potentially discover agonists which maintain the antilipolytic effects of niacin accessed by a decrease in circulating non-esterified fatty acids (NEFA) and thereby perhaps the lipid/lipoprotein effects, but avoid the flushing effects. Niacin 159-165 hydroxycarboxylic acid receptor 2 Homo sapiens 53-57 25773497-3 2015 The discovery of hydroxy-carboxylic acid receptor 2 (HCA2) as a high affinity receptor for niacin has opened avenues to investigate the mechanism of action of niacin, and to potentially discover agonists which maintain the antilipolytic effects of niacin accessed by a decrease in circulating non-esterified fatty acids (NEFA) and thereby perhaps the lipid/lipoprotein effects, but avoid the flushing effects. Niacin 159-165 hydroxycarboxylic acid receptor 2 Homo sapiens 17-51 25773497-3 2015 The discovery of hydroxy-carboxylic acid receptor 2 (HCA2) as a high affinity receptor for niacin has opened avenues to investigate the mechanism of action of niacin, and to potentially discover agonists which maintain the antilipolytic effects of niacin accessed by a decrease in circulating non-esterified fatty acids (NEFA) and thereby perhaps the lipid/lipoprotein effects, but avoid the flushing effects. Niacin 159-165 hydroxycarboxylic acid receptor 2 Homo sapiens 53-57 25599616-2 2015 GPR109A is activated by niacin and mediates the anti-lipolytic effects. Niacin 24-30 hydroxycarboxylic acid receptor 2 Homo sapiens 0-7 25320346-1 2014 Many of the beneficial and adverse effects of niacin are mediated via a G protein receptor, G protein-coupled receptor 109A/hydroxycarboxylic acid 2 receptor (GPR109A/HCA2), which is highly expressed in adipose tissue and macrophages. Niacin 46-52 hydroxycarboxylic acid receptor 2 Homo sapiens 159-166 25455298-4 2014 Thus, niacin supplementation may serve three purposes: reduce inflammation through GPR109A-related mechanisms, increase dopamine synthesis in the striatum through NADPH supply and increase NAD/NADH ratio to boost mitochondrial functions. Niacin 6-12 hydroxycarboxylic acid receptor 2 Homo sapiens 83-90 25455298-7 2014 For the first time here we propose the roles of GPR109A and its agonists including niacin in CNS pathology. Niacin 83-89 hydroxycarboxylic acid receptor 2 Homo sapiens 48-55 25455298-8 2014 Moreover we predict that the neuroprotective roles of either niacin or butyrates in CNS occur via GPR109A. Niacin 61-67 hydroxycarboxylic acid receptor 2 Homo sapiens 98-105 25463108-9 2014 Activation of this receptor with either acifran or MK-1903 recapitulated niacin-induced improvements in HMVEC tube formation, while GPR109A siRNA diminished the effect of niacin. Niacin 171-177 hydroxycarboxylic acid receptor 2 Homo sapiens 132-139 25320346-1 2014 Many of the beneficial and adverse effects of niacin are mediated via a G protein receptor, G protein-coupled receptor 109A/hydroxycarboxylic acid 2 receptor (GPR109A/HCA2), which is highly expressed in adipose tissue and macrophages. Niacin 46-52 hydroxycarboxylic acid receptor 2 Homo sapiens 167-171 25329911-2 2014 Niacin has a high affinity for GPR109A, an anti-inflammatory receptor. Niacin 0-6 hydroxycarboxylic acid receptor 2 Homo sapiens 31-38 25911818-6 2014 Specifically, all of the candidate compounds" interaction with nicotinic acid receptor was similar to nicotinic acid, and their docking scores were all higher than that of nicotinic acid, but their druggability remained to be further studied. Niacin 102-116 hydroxycarboxylic acid receptor 2 Homo sapiens 63-86 25375133-1 2014 Niacin has been demonstrated to activate a PI3K/Akt signaling cascade to prevent brain damage after stroke and UV-induced skin damage; however, the underlying molecular mechanisms for HCA2-induced Akt activation remain to be elucidated. Niacin 0-6 hydroxycarboxylic acid receptor 2 Homo sapiens 184-188 25375133-2 2014 Using CHO-K1 cells stably expressing HCA2 and A431 cells, a human epidermoid cell line with high levels of endogenous expression of functional HCA2 receptors, we first demonstrated that niacin induced a robust Akt phosphorylation at both Thr308 and Ser473 in a time-dependent fashion, with a maximal activation at 5 min and a subsequent reduction to baseline by 30 min through HCA2, and that the activation was significantly blocked by pertussis toxin. Niacin 186-192 hydroxycarboxylic acid receptor 2 Homo sapiens 37-41 25375133-2 2014 Using CHO-K1 cells stably expressing HCA2 and A431 cells, a human epidermoid cell line with high levels of endogenous expression of functional HCA2 receptors, we first demonstrated that niacin induced a robust Akt phosphorylation at both Thr308 and Ser473 in a time-dependent fashion, with a maximal activation at 5 min and a subsequent reduction to baseline by 30 min through HCA2, and that the activation was significantly blocked by pertussis toxin. Niacin 186-192 hydroxycarboxylic acid receptor 2 Homo sapiens 143-147 25375133-2 2014 Using CHO-K1 cells stably expressing HCA2 and A431 cells, a human epidermoid cell line with high levels of endogenous expression of functional HCA2 receptors, we first demonstrated that niacin induced a robust Akt phosphorylation at both Thr308 and Ser473 in a time-dependent fashion, with a maximal activation at 5 min and a subsequent reduction to baseline by 30 min through HCA2, and that the activation was significantly blocked by pertussis toxin. Niacin 186-192 hydroxycarboxylic acid receptor 2 Homo sapiens 143-147 24662263-3 2014 The amide form of nicotinic acid, named nicotinamide, acts as a vitamin although neither activates the GPR109A nor exhibits the pharmacological properties of nicotinic acid. Niacin 18-32 hydroxycarboxylic acid receptor 2 Homo sapiens 103-110 24767308-2 2014 Nicotinic acid (NA), a carboxylated pyridine derivative, inhibits lipolysis in adipocytes by activation of the orphan NA receptor (HM74A) and is applied to treat hyperlipidemia. Niacin 0-14 hydroxycarboxylic acid receptor 2 Homo sapiens 131-136 24768191-2 2014 Niacin directly activates both GPR-109A in leukocytes and the heme oxygenase-1 pathway, promoting strong anti-inflammatory and antioxidative effects, as well as induces immediate production of prostaglandin D2, leading to endothelial vasodilation. Niacin 0-6 hydroxycarboxylic acid receptor 2 Homo sapiens 31-39 24433041-5 2014 Indeed, arrestin pathway-selective agonists for the type 1 parathyroid hormone and angiotensin AT1 receptors, and G protein pathway-selective agonists for the GPR109A nicotinic acid and mu-opioid receptors, have demonstrated unique, and potentially therapeutic, efficacy in cell-based assays and preclinical animal models. Niacin 167-181 hydroxycarboxylic acid receptor 2 Homo sapiens 159-166 23770183-1 2013 Until recently, the anti-atherosclerotic effects of niacin were attributed primarily to its lipid modification properties mediated by adipocyte G-protein coupled receptor GPR109A, though recent studies have raised significant doubts about this mechanism. Niacin 52-58 hydroxycarboxylic acid receptor 2 Homo sapiens 171-178 24371223-1 2014 GPR109A, a G-protein-coupled receptor, is activated by niacin and butyrate. Niacin 55-61 hydroxycarboxylic acid receptor 2 Homo sapiens 0-7 23770183-9 2013 These studies provide key insights into mechanisms by which GPR109A may influence cholesterol efflux in macrophages; a process that may be at least partially responsible for niacin"s anti-atherosclerotic activity. Niacin 174-180 hydroxycarboxylic acid receptor 2 Homo sapiens 60-67 24184940-3 2013 Studies of the purported niacin receptor, GPR109A, indicate that niacin-mediated fatty acid-lowering and flushing are dependent on niacin binding to this receptor, whereas the lipid-altering effects of niacin may be independent of the interaction of niacin with the receptor. Niacin 25-31 hydroxycarboxylic acid receptor 2 Homo sapiens 42-49 24184940-3 2013 Studies of the purported niacin receptor, GPR109A, indicate that niacin-mediated fatty acid-lowering and flushing are dependent on niacin binding to this receptor, whereas the lipid-altering effects of niacin may be independent of the interaction of niacin with the receptor. Niacin 65-71 hydroxycarboxylic acid receptor 2 Homo sapiens 42-49 24184940-3 2013 Studies of the purported niacin receptor, GPR109A, indicate that niacin-mediated fatty acid-lowering and flushing are dependent on niacin binding to this receptor, whereas the lipid-altering effects of niacin may be independent of the interaction of niacin with the receptor. Niacin 65-71 hydroxycarboxylic acid receptor 2 Homo sapiens 42-49 24184940-3 2013 Studies of the purported niacin receptor, GPR109A, indicate that niacin-mediated fatty acid-lowering and flushing are dependent on niacin binding to this receptor, whereas the lipid-altering effects of niacin may be independent of the interaction of niacin with the receptor. Niacin 65-71 hydroxycarboxylic acid receptor 2 Homo sapiens 42-49 23770183-2 2013 In fact, in rodents it has recently been demonstrated that niacin inhibits progression of atherosclerosis through actions on immune cells, particularly via macrophage-expressed GPR109A, independent of lipid-modifying properties. Niacin 59-65 hydroxycarboxylic acid receptor 2 Homo sapiens 177-184 23770183-5 2013 In Langerhans cells, niacin initiates GPR109A-mediated signaling pathways (Erk1/2 and Ca(2+)) responsible for the release of vasodilatory prostanoids, while the synthetic GPR109A agonist MK-0354 fails to elicit any signaling, providing a mechanistic basis for the latter compound"s inability to cause flushing. Niacin 21-27 hydroxycarboxylic acid receptor 2 Homo sapiens 38-45 23770183-5 2013 In Langerhans cells, niacin initiates GPR109A-mediated signaling pathways (Erk1/2 and Ca(2+)) responsible for the release of vasodilatory prostanoids, while the synthetic GPR109A agonist MK-0354 fails to elicit any signaling, providing a mechanistic basis for the latter compound"s inability to cause flushing. Niacin 21-27 hydroxycarboxylic acid receptor 2 Homo sapiens 171-178 23770183-7 2013 Also, in macrophages niacin and GPR109A full agonists induce Erk1/2 and Ca(2+) signaling, release of prostanoids, upregulation of cholesterol transporters ABCA1 and ABCG1 and stimulation of reverse cholesterol transport in GPR109A dependent manner. Niacin 21-27 hydroxycarboxylic acid receptor 2 Homo sapiens 223-230 23526298-3 2013 As GPR109A"s primary pharmacological ligand in clinical use, niacin has been used for over 50 years in the treatment of cardiovascular disease, mainly due to its favourable effects on plasma lipoproteins. Niacin 61-67 hydroxycarboxylic acid receptor 2 Homo sapiens 3-10 23526298-4 2013 However, it has become apparent that niacin also possesses lipoprotein-independent effects that influence inflammatory pathways mediated through GPR109A. Niacin 37-43 hydroxycarboxylic acid receptor 2 Homo sapiens 145-152 22435740-1 2012 G-protein coupled receptor (GPCR) GPR109a is a molecular target for nicotinic acid and is expressed in adipocytes, spleen, and immune cells. Niacin 68-82 hydroxycarboxylic acid receptor 2 Homo sapiens 34-41 22743741-0 2012 Role of HCA2 (GPR109A) in nicotinic acid and fumaric acid ester-induced effects on the skin. Niacin 26-40 hydroxycarboxylic acid receptor 2 Homo sapiens 8-12 22743741-0 2012 Role of HCA2 (GPR109A) in nicotinic acid and fumaric acid ester-induced effects on the skin. Niacin 26-40 hydroxycarboxylic acid receptor 2 Homo sapiens 14-21 22962331-2 2012 Our recent studies have demonstrated that the niacin-induced internalization of HCA2 receptors is regulated by G protein-coupled receptor kinase (GRK) 2 and arrestin3 and that internalized receptors rapidly recycle back to the cell surface. Niacin 46-52 hydroxycarboxylic acid receptor 2 Homo sapiens 80-84 22914620-1 2012 The antiatherogenic drug nicotinic acid (niacin) has antidyslipidemic effects independent of free fatty acid suppression mediated by its receptor HCA2 (GPR109A) (Lauring et al., this issue). Niacin 25-39 hydroxycarboxylic acid receptor 2 Homo sapiens 152-159 22914621-3 2012 It is well established that activation of the seven-transmembrane G(i)-coupled receptor GPR109A on Langerhans cells results in release of prostaglandin D2, which mediates the well-known flushing side effect of niacin. Niacin 210-216 hydroxycarboxylic acid receptor 2 Homo sapiens 88-95 22914621-4 2012 Niacin activation of GPR109A on adipocytes also mediates the transient reduction of plasma free fatty acid (FFA) levels characteristic of niacin, which has been long hypothesized to be the mechanism underlying the changes in the serum lipid profile. Niacin 0-6 hydroxycarboxylic acid receptor 2 Homo sapiens 21-28 22914621-4 2012 Niacin activation of GPR109A on adipocytes also mediates the transient reduction of plasma free fatty acid (FFA) levels characteristic of niacin, which has been long hypothesized to be the mechanism underlying the changes in the serum lipid profile. Niacin 138-144 hydroxycarboxylic acid receptor 2 Homo sapiens 21-28 21768093-1 2011 Nicotinic acid (niacin) has been widely used as a lipid-lowering drug for several decades, and recently, orphan G protein-coupled receptor GPR109A has been identified as a receptor for niacin. Niacin 0-14 hydroxycarboxylic acid receptor 2 Homo sapiens 139-146 22267479-0 2012 Anti-inflammatory effects of nicotinic acid in human monocytes are mediated by GPR109A dependent mechanisms. Niacin 29-43 hydroxycarboxylic acid receptor 2 Homo sapiens 79-86 21943747-1 2011 Responses to pharmacological doses of niacin, an agonist for GPR109A (niacin receptor), were different in cattle than in humans and rodents. Niacin 38-44 hydroxycarboxylic acid receptor 2 Homo sapiens 61-68 21943747-8 2011 Finally, analysis of the putative bovine GPR109A sequence verified that AA residues required for binding niacin in human GPR109A are conserved, suggesting that the bovine sequence identified encodes a functional niacin receptor. Niacin 105-111 hydroxycarboxylic acid receptor 2 Homo sapiens 41-48 21943747-8 2011 Finally, analysis of the putative bovine GPR109A sequence verified that AA residues required for binding niacin in human GPR109A are conserved, suggesting that the bovine sequence identified encodes a functional niacin receptor. Niacin 105-111 hydroxycarboxylic acid receptor 2 Homo sapiens 121-128 21768093-5 2011 Furthermore, time course experiments with different kinase inhibitors demonstrated that GPR109A induced ERK1/2 activation via the matrix metalloproteinase/epidermal growth factor receptor transactivation pathway at both early and later time points (2-5 min); this pathway was distinct from the PKC pathway-mediated ERK1/2 phosphorylation that occurs at early time points (<=2 min) in response to niacin. Niacin 399-405 hydroxycarboxylic acid receptor 2 Homo sapiens 88-95 21768093-1 2011 Nicotinic acid (niacin) has been widely used as a lipid-lowering drug for several decades, and recently, orphan G protein-coupled receptor GPR109A has been identified as a receptor for niacin. Niacin 16-22 hydroxycarboxylic acid receptor 2 Homo sapiens 139-146 21768093-4 2011 Using CHO-K1 cells stably expressing GPR109A and A431 cells, which are a human epidermoid cell line with high levels of endogenous expression of functional GPR109A receptors, we found that activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) by niacin was rapid, peaking at 5 min, and was significantly blocked by pertussis toxin. Niacin 262-268 hydroxycarboxylic acid receptor 2 Homo sapiens 156-163 20664168-1 2010 The use of niacin to improve plasma lipid levels and reduce risk of myocardial infarction is limited by noxious skin effects that result from stimulation of G protein-coupled receptor 109A (GPR109A) in skin immune cells. Niacin 11-17 hydroxycarboxylic acid receptor 2 Homo sapiens 157-188 21907911-7 2011 HCA(2) was first discovered as the molecular target of the antidyslipidemic drug nicotinic acid (or niacin). Niacin 81-95 hydroxycarboxylic acid receptor 2 Homo sapiens 0-6 21907911-7 2011 HCA(2) was first discovered as the molecular target of the antidyslipidemic drug nicotinic acid (or niacin). Niacin 100-106 hydroxycarboxylic acid receptor 2 Homo sapiens 0-6 21907911-9 2011 Recently, it has been shown that the major side effect of nicotinic acid, skin flushing, is mediated by HCA(2) receptors on keratinocytes, as well as on Langerhans cells in the skin. Niacin 58-72 hydroxycarboxylic acid receptor 2 Homo sapiens 104-110 20615702-2 2010 5-Alkyl and aryl-pyrazole-acids have been identified as a new class of selective, small-molecule, agonists of the human orphan G-protein-coupled receptor GPR109a, a high affinity receptor for the HDL-raising drug nicotinic acid. Niacin 213-227 hydroxycarboxylic acid receptor 2 Homo sapiens 154-161 21418500-3 2011 Recently, the receptor for niacin, GPR109A, was discovered. Niacin 27-33 hydroxycarboxylic acid receptor 2 Homo sapiens 35-42 21418500-4 2011 GPR109A in the adipocyte mediates a niacin-induced inhibition of lipolysis, which could play a crucial part in its role as a lipid-modifying drug. Niacin 36-42 hydroxycarboxylic acid receptor 2 Homo sapiens 0-7 21418500-5 2011 GPR109A in epidermal Langerhans cells mediates flushing, an unwanted side effect of niacin therapy. Niacin 84-90 hydroxycarboxylic acid receptor 2 Homo sapiens 0-7 21655214-2 2011 Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through G(i)-mediated inhibition of adenylyl cyclase. Niacin 0-14 hydroxycarboxylic acid receptor 2 Homo sapiens 89-96 20936932-5 2010 After the discovery of the nicotinic acid receptor GPR109A on adipocytes and immune cells, novel direct immunomodulatory properties of nicotinic acid have been identified. Niacin 27-41 hydroxycarboxylic acid receptor 2 Homo sapiens 51-58 20664168-1 2010 The use of niacin to improve plasma lipid levels and reduce risk of myocardial infarction is limited by noxious skin effects that result from stimulation of G protein-coupled receptor 109A (GPR109A) in skin immune cells. Niacin 11-17 hydroxycarboxylic acid receptor 2 Homo sapiens 190-197 19461950-6 2009 By comparison, nicotinic acid provides even greater levels of NAD than nicotinamide in many tissues, while additionally activating the PPARgamma-dependent pathway already shown to provide relief in animal models of MS after activation of GPR109a/HM74a. Niacin 15-29 hydroxycarboxylic acid receptor 2 Homo sapiens 238-245 19781706-1 2010 OBJECTIVE: A major site of action for the atheroprotective drug nicotinic acid (NA) is adipose tissue, via the G-protein-coupled receptor, GPR109A. Niacin 64-78 hydroxycarboxylic acid receptor 2 Homo sapiens 139-146 19627285-5 2009 The recent discovery of the niacin G-protein-coupled receptor HM74A (GPR109A) has clarified the distinction between the mechanism whereby niacin exerts its therapeutic effects and the mechanisms responsible for the generation of side effects. Niacin 28-34 hydroxycarboxylic acid receptor 2 Homo sapiens 62-67 19627285-5 2009 The recent discovery of the niacin G-protein-coupled receptor HM74A (GPR109A) has clarified the distinction between the mechanism whereby niacin exerts its therapeutic effects and the mechanisms responsible for the generation of side effects. Niacin 28-34 hydroxycarboxylic acid receptor 2 Homo sapiens 69-76 19307116-2 2009 5-Alkyl and aryl-pyrazole-tetrazoles have been identified as a new class of selective, small-molecule, agonists of the human G-protein-coupled receptor GPR109a, a high affinity receptor for the HDL-raising drug nicotinic acid. Niacin 211-225 hydroxycarboxylic acid receptor 2 Homo sapiens 152-159 19080727-4 2009 Flushing, an adverse effect of niacin, results from niacin receptor GPR109A-mediated production of prostaglandin D2 and E2 via DP1 and EP2/4 receptors. Niacin 31-37 hydroxycarboxylic acid receptor 2 Homo sapiens 68-75 19519459-0 2009 HM74a agonists: will they be the new generation of nicotinic acid? Niacin 51-65 hydroxycarboxylic acid receptor 2 Homo sapiens 0-5 19519459-1 2009 The discovery of HM74a as a high affinity receptor for nicotinic acid has opened up new areas for investigation. Niacin 55-69 hydroxycarboxylic acid receptor 2 Homo sapiens 17-22 19519459-4 2009 These surprising results lead to questions about the reality of HM74a as the unique receptor responsible for the lipid modulating effects of nicotinic acid. Niacin 141-155 hydroxycarboxylic acid receptor 2 Homo sapiens 64-69 19223991-8 2009 Activation of GPR109A by niacin and beta-HB was demonstrated in ARPE-19 cells by cAMP assay. Niacin 25-31 hydroxycarboxylic acid receptor 2 Homo sapiens 14-21 20460384-1 2010 Nicotinic acid (niacin) has been widely used as a favorable lipid-lowering drug for several decades, and the orphan G protein-coupled receptor GPR109A has been identified to be a receptor for niacin. Niacin 0-14 hydroxycarboxylic acid receptor 2 Homo sapiens 143-150 20460384-1 2010 Nicotinic acid (niacin) has been widely used as a favorable lipid-lowering drug for several decades, and the orphan G protein-coupled receptor GPR109A has been identified to be a receptor for niacin. Niacin 16-22 hydroxycarboxylic acid receptor 2 Homo sapiens 143-150 20460384-2 2010 Mechanistic investigations have shown that as a G(i)-coupled receptor, GPR109A inhibits adenylate cyclase activity upon niacin activation, thereby inhibiting free fatty acid liberation. Niacin 120-126 hydroxycarboxylic acid receptor 2 Homo sapiens 71-78 19461950-6 2009 By comparison, nicotinic acid provides even greater levels of NAD than nicotinamide in many tissues, while additionally activating the PPARgamma-dependent pathway already shown to provide relief in animal models of MS after activation of GPR109a/HM74a. Niacin 15-29 hydroxycarboxylic acid receptor 2 Homo sapiens 246-251 17932499-1 2008 G protein-coupled receptor (GPR)109A (HM74A) is a G(i) protein-coupled receptor, which is activated by nicotinic acid (NA), a lipid-lowering drug. Niacin 103-117 hydroxycarboxylic acid receptor 2 Homo sapiens 28-36 18722346-6 2008 We show that monomethylfumarate activates GPR109A in a calcium based aequorin assay, cAMP assay and demonstrate competitive binding with nicotinic acid. Niacin 137-151 hydroxycarboxylic acid receptor 2 Homo sapiens 42-49 18520725-2 2008 RECENT FINDINGS: Flushing, an adverse effect of niacin, results from GPR109A-mediated production of prostaglandin D2 and E2 in Langerhans" cells which act on DP1 and EP2/4 receptors in dermal capillaries causing their vasodilatation. Niacin 48-54 hydroxycarboxylic acid receptor 2 Homo sapiens 69-76 18520725-7 2008 SUMMARY: Recent developments suggest that the niacin receptor GPR109A is involved in flushing, but it does not explain multiple actions of niacin. Niacin 46-52 hydroxycarboxylic acid receptor 2 Homo sapiens 62-69 17932499-1 2008 G protein-coupled receptor (GPR)109A (HM74A) is a G(i) protein-coupled receptor, which is activated by nicotinic acid (NA), a lipid-lowering drug. Niacin 103-117 hydroxycarboxylic acid receptor 2 Homo sapiens 38-43 17430113-17 2007 Distinct among the NAD precursors, nicotinic acid specifically activates the g-protein coupled receptor (GPCR) GPR109a to produce the IDO-inducing tolerogenic prostaglandins PGE(2) and PGD(2). Niacin 35-49 hydroxycarboxylic acid receptor 2 Homo sapiens 111-118 17659487-2 2007 The recent discovery of a G-protein-coupled receptor target for niacin (termed GPR109alpha) has stimulated interest in the discovery of new compounds with niacin-like effects on lipids, but with fewer adverse effects. Niacin 64-70 hydroxycarboxylic acid receptor 2 Homo sapiens 79-90 17659487-4 2007 The advances made in both these areas may help to determine whether GPR109alpha is the molecular target responsible for the beneficial anti-atherogenic effects of niacin. Niacin 163-169 hydroxycarboxylic acid receptor 2 Homo sapiens 68-79 17554232-10 2007 The recent discovery of the G-protein-coupled receptor GPR109A, which mediates the antilipolytic effects induced by nicotinic acid in adipocytes as well as cutaneous vasodilation, allows the development of new agents interacting with this receptor. Niacin 116-130 hydroxycarboxylic acid receptor 2 Homo sapiens 55-62 18047854-10 2007 GPR109A-mediated production of prostaglandin D2 in macrophages and Langerhan cells causes skin capillary vasodilation and explains, in part, niacin"s effect on flushing. Niacin 141-147 hydroxycarboxylic acid receptor 2 Homo sapiens 0-7 17452318-2 2007 The therapeutic actions of nicotinic acid are mediated by GPR109A, a Gi protein-coupled receptor, expressed primarily on adipocytes, Langerhans cells, and macrophage. Niacin 27-41 hydroxycarboxylic acid receptor 2 Homo sapiens 58-65 17452318-7 2007 We have identified a number of GPR109A pyrazole agonists that are capable of fully inhibiting lipolysis in vitro and in vivo and not only fail to elicit a flushing response but can antagonize the ability of nicotinic acid to elicit a flush response in vivo. Niacin 207-221 hydroxycarboxylic acid receptor 2 Homo sapiens 31-38 17238156-3 2007 This receptor responds to both nicotinic acid and the ketone body beta-hydroxybutyrate, the latter thought to be the more probable endogenous ligand for HM74A. Niacin 31-45 hydroxycarboxylic acid receptor 2 Homo sapiens 153-158 17238156-8 2007 HM74A has also been linked to one of the major side effects of nicotinic acid, that is, flushing, since this receptor subtype also occurs in skin immune cells. Niacin 63-77 hydroxycarboxylic acid receptor 2 Homo sapiens 0-5 16322787-0 2005 Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid. Niacin 69-83 hydroxycarboxylic acid receptor 2 Homo sapiens 25-32 16322797-0 2005 GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing. Niacin 32-46 hydroxycarboxylic acid receptor 2 Homo sapiens 16-21 16322797-3 2005 Recently, a G-protein-coupled receptor, termed GPR109A (HM74A in humans, PUMA-G in mice), was described and shown to mediate the nicotinic acid-induced antilipolytic effects in adipocytes. Niacin 129-143 hydroxycarboxylic acid receptor 2 Homo sapiens 47-54 16322797-3 2005 Recently, a G-protein-coupled receptor, termed GPR109A (HM74A in humans, PUMA-G in mice), was described and shown to mediate the nicotinic acid-induced antilipolytic effects in adipocytes. Niacin 129-143 hydroxycarboxylic acid receptor 2 Homo sapiens 56-61 17124637-2 2007 The molecular target of nicotinic acid was unknown until the recent revelation of human G-coupled receptor HM74a as the high affinity receptor for nicotinic acid. Niacin 24-38 hydroxycarboxylic acid receptor 2 Homo sapiens 107-112 17124637-2 2007 The molecular target of nicotinic acid was unknown until the recent revelation of human G-coupled receptor HM74a as the high affinity receptor for nicotinic acid. Niacin 147-161 hydroxycarboxylic acid receptor 2 Homo sapiens 107-112 17008386-3 2006 Nicotinic acid-induced flushing has been shown to be mediated by the nicotinic acid receptor GPR109A and to involve the formation of vasodilatory prostanoids. Niacin 0-14 hydroxycarboxylic acid receptor 2 Homo sapiens 93-100 16674924-1 2006 HM74A is a G protein-coupled receptor for nicotinic acid (niacin), which has been used clinically to treat dyslipidemia for decades. Niacin 42-56 hydroxycarboxylic acid receptor 2 Homo sapiens 0-5 16674924-1 2006 HM74A is a G protein-coupled receptor for nicotinic acid (niacin), which has been used clinically to treat dyslipidemia for decades. Niacin 58-64 hydroxycarboxylic acid receptor 2 Homo sapiens 0-5 16386710-0 2006 Niacin induces PPARgamma expression and transcriptional activation in macrophages via HM74 and HM74a-mediated induction of prostaglandin synthesis pathways. Niacin 0-6 hydroxycarboxylic acid receptor 2 Homo sapiens 95-100 16386710-2 2006 HM74a mediates the pharmacological anti-lipolytic effects of niacin in adipocytes by reducing intracellular cyclic AMP (cAMP) and inhibiting release of free fatty acids into the circulation. Niacin 61-67 hydroxycarboxylic acid receptor 2 Homo sapiens 0-5 16386710-8 2006 Niacin also induced PPARgamma transcriptional activity in HM74 and HM74a CHO cell transfectants, although not in vector-only control cells. Niacin 0-6 hydroxycarboxylic acid receptor 2 Homo sapiens 67-72 16386710-11 2006 These results indicate that HM74 and HM74a can mediate macrophage responses to niacin via activation of the prostaglandin synthesis pathway and induction and activation of PPARgamma. Niacin 79-85 hydroxycarboxylic acid receptor 2 Homo sapiens 37-42 16322787-0 2005 Flushing out the role of GPR109A (HM74A) in the clinical efficacy of nicotinic acid. Niacin 69-83 hydroxycarboxylic acid receptor 2 Homo sapiens 34-39 16322787-1 2005 The recent discovery of the G(i) protein-coupled receptor GPR109A (HM74A in humans; PUMA-G in mice) as a receptor for nicotinic acid has provided the opportunity to gain greater understanding of the underlying biology contributing to the clinical efficacy (increases in HDL, decreases in VLDL, LDL, and triglycerides) and the characteristic side-effect profile of nicotinic acid. Niacin 118-132 hydroxycarboxylic acid receptor 2 Homo sapiens 58-65 16322787-1 2005 The recent discovery of the G(i) protein-coupled receptor GPR109A (HM74A in humans; PUMA-G in mice) as a receptor for nicotinic acid has provided the opportunity to gain greater understanding of the underlying biology contributing to the clinical efficacy (increases in HDL, decreases in VLDL, LDL, and triglycerides) and the characteristic side-effect profile of nicotinic acid. Niacin 118-132 hydroxycarboxylic acid receptor 2 Homo sapiens 67-72 16322787-1 2005 The recent discovery of the G(i) protein-coupled receptor GPR109A (HM74A in humans; PUMA-G in mice) as a receptor for nicotinic acid has provided the opportunity to gain greater understanding of the underlying biology contributing to the clinical efficacy (increases in HDL, decreases in VLDL, LDL, and triglycerides) and the characteristic side-effect profile of nicotinic acid. Niacin 364-378 hydroxycarboxylic acid receptor 2 Homo sapiens 58-65 16322787-1 2005 The recent discovery of the G(i) protein-coupled receptor GPR109A (HM74A in humans; PUMA-G in mice) as a receptor for nicotinic acid has provided the opportunity to gain greater understanding of the underlying biology contributing to the clinical efficacy (increases in HDL, decreases in VLDL, LDL, and triglycerides) and the characteristic side-effect profile of nicotinic acid. Niacin 364-378 hydroxycarboxylic acid receptor 2 Homo sapiens 67-72 16322787-2 2005 GPR109A has been proven to be the molecular target for the actions of nicotinic acid on adipose tissue, and in this issue of the JCI, Benyo et al. Niacin 70-84 hydroxycarboxylic acid receptor 2 Homo sapiens 0-7 16322787-3 2005 have confirmed the involvement of GPR109A in the nicotinic acid-induced flushing response, a common side effect. Niacin 49-63 hydroxycarboxylic acid receptor 2 Homo sapiens 34-41 16322787-4 2005 The involvement of GPR109A in both the desirable and undesirable clinical actions of nicotinic acid raises interesting questions regarding the function of this receptor. Niacin 85-99 hydroxycarboxylic acid receptor 2 Homo sapiens 19-26 16018973-0 2005 Niacin mediates lipolysis in adipose tissue through its G-protein coupled receptor HM74A. Niacin 0-6 hydroxycarboxylic acid receptor 2 Homo sapiens 83-88 16018973-2 2005 We present our studies to demonstrate that HM74A, but not HM74, binds niacin at high affinities and effectively mediates Gi signaling events in human embryonic kidney HEK293 cells as well as in 3T3L1 adipocytes expressing HM74A. Niacin 70-76 hydroxycarboxylic acid receptor 2 Homo sapiens 43-48 16018973-3 2005 Furthermore, HM74A, but not HM74, expressed in differentiated 3T3L1 adipocytes effectively mediated inhibition of lipolysis by niacin. Niacin 127-133 hydroxycarboxylic acid receptor 2 Homo sapiens 13-18 16018973-4 2005 Our results provided direct evidence indicating that HM74A, but not HM74, was sufficient to mediate anti-lipolytic effect of niacin in adipose tissue. Niacin 125-131 hydroxycarboxylic acid receptor 2 Homo sapiens 53-58 12646212-3 2003 Here we show that a novel GPCR, designated HM74b because of its high similarity to HM74, is a receptor for nicotinic acid. Niacin 107-121 hydroxycarboxylic acid receptor 2 Homo sapiens 43-48 12522134-6 2003 We then describe the subsequent identification of HM74A in follow-up bioinformatics searches and demonstrate that it acts as a high affinity receptor for nicotinic acid and other compounds with related pharmacology. Niacin 154-168 hydroxycarboxylic acid receptor 2 Homo sapiens 50-55 12522134-7 2003 The discovery of HM74A as a molecular target for nicotinic acid may facilitate the discovery of superior drug molecules to treat dyslipidemia. Niacin 49-63 hydroxycarboxylic acid receptor 2 Homo sapiens 17-22 15580557-1 2005 HM74 (GPR109B) and the highly homologous gene, HM74A (GPR109A) code for Gi-G protein-coupled orphan receptors that recently have been discovered to be involved in the metabolic effects of niacin. Niacin 188-194 hydroxycarboxylic acid receptor 2 Homo sapiens 47-52 15580557-1 2005 HM74 (GPR109B) and the highly homologous gene, HM74A (GPR109A) code for Gi-G protein-coupled orphan receptors that recently have been discovered to be involved in the metabolic effects of niacin. Niacin 188-194 hydroxycarboxylic acid receptor 2 Homo sapiens 54-61 15580557-3 2005 The novel role of the adjacent HM74 and HM74A genes in the metabolism of niacin may provide new targets for drug development. Niacin 73-79 hydroxycarboxylic acid receptor 2 Homo sapiens 40-45 12646212-5 2003 Nicotinic acid and Acipimox inhibit forskolin-stimulated intracellular cAMP accumulation in human HM74b-expressing cells and activate GTP gamma S binding in a dose-dependent manner. Niacin 0-14 hydroxycarboxylic acid receptor 2 Homo sapiens 98-103 12646212-6 2003 [3H]Nicotinic acid specifically binds to HM74b-expressing membrane and its binding is replaced by Acipimox. Niacin 4-18 hydroxycarboxylic acid receptor 2 Homo sapiens 41-46 34866904-1 2021 The transmembrane G-protein coupled receptor GPR109A has been previously shown to function as a receptor for niacin in mediating antilipolytic effects. Niacin 109-115 hydroxycarboxylic acid receptor 2 Homo sapiens 45-52 17008871-5 2006 Cells expressing GPR109A mRNA were further assayed for PGD(2) release in response to nicotinic acid. Niacin 85-99 hydroxycarboxylic acid receptor 2 Homo sapiens 17-24 17008871-12 2006 These results suggest that nicotinic acid mediates its flushing side effect by interacting with GPR109A on skin Langerhans cells, resulting in release of PGD(2). Niacin 27-41 hydroxycarboxylic acid receptor 2 Homo sapiens 96-103 34743990-7 2022 We also review studies that demonstrate that the functional effect of niacin is partially due to the activation of its cell surface receptor, GPR109a. Niacin 70-76 hydroxycarboxylic acid receptor 2 Homo sapiens 142-149 34916973-0 2021 Inflammation and JNK"s Role in Niacin-GPR109A Diminished Flushed Effect in Microglial and Neuronal Cells With Relevance to Schizophrenia. Niacin 31-37 hydroxycarboxylic acid receptor 2 Homo sapiens 38-45 34866904-3 2021 Thus, it is important to understand niacin-GPR109A interactions, which can be beneficial for the development of alternate drugs having antilipolytic effects with less or no side effects. Niacin 36-42 hydroxycarboxylic acid receptor 2 Homo sapiens 43-50 34866904-4 2021 To get into the structural insights on niacin binding to GPR109A, we have performed 100 nanoseconds long all-atom MD simulations of five niacin-GPR109A complexes (automatically docked pose 0, and randomly placed niacin in poses 1 to 4 in the receptor crevice) and analyzed using binding free energy calculations and H-bond analysis. Niacin 39-45 hydroxycarboxylic acid receptor 2 Homo sapiens 57-64 34866904-4 2021 To get into the structural insights on niacin binding to GPR109A, we have performed 100 nanoseconds long all-atom MD simulations of five niacin-GPR109A complexes (automatically docked pose 0, and randomly placed niacin in poses 1 to 4 in the receptor crevice) and analyzed using binding free energy calculations and H-bond analysis. Niacin 137-143 hydroxycarboxylic acid receptor 2 Homo sapiens 144-151 33674782-5 2021 We confirmed known metabolite-target pairs such as nicotinic acid-GPR109a or linoleoyl ethanolamide-GPR119 and inferred interactions of interest including oleanolic acid-GABRG2 and alpha-CEHC-THRB. Niacin 51-65 hydroxycarboxylic acid receptor 2 Homo sapiens 66-73 34803497-2 2021 Our previous studies found that niacin has anti-inflammatory effect, and the realization of this function depends on GPR109A. Niacin 32-38 hydroxycarboxylic acid receptor 2 Homo sapiens 117-124 34681211-6 2021 Representative compounds from each synthesized series were able to decrease the lipopolysaccharide-induced gene expression and secretion of proinflammatory cytokines (IL-6, TNF-alpha) and of a chemokine (MCP-1) in THP-1 macrophages, resembling the effect of HCA2/GPR109A ligand niacin and the endogenous ligand propionate. Niacin 278-284 hydroxycarboxylic acid receptor 2 Homo sapiens 258-262 34681211-6 2021 Representative compounds from each synthesized series were able to decrease the lipopolysaccharide-induced gene expression and secretion of proinflammatory cytokines (IL-6, TNF-alpha) and of a chemokine (MCP-1) in THP-1 macrophages, resembling the effect of HCA2/GPR109A ligand niacin and the endogenous ligand propionate. Niacin 278-284 hydroxycarboxylic acid receptor 2 Homo sapiens 263-270 33708203-3 2021 Butyrate and niacin, endogenous and exogenous ligands of HCA2, have been reported to play an essential role in maintaining intestinal homeostasis. Niacin 13-19 hydroxycarboxylic acid receptor 2 Homo sapiens 57-61 33550969-6 2021 Very recently, the G protein coupled receptor (GPCR); GPR109A located on the adipocytes has been identified as the receptor for activation of niacin. Niacin 142-148 hydroxycarboxylic acid receptor 2 Homo sapiens 54-61 31617441-0 2019 Activation of HCAR2 by niacin: benefits beyond lipid lowering. Niacin 23-29 hydroxycarboxylic acid receptor 2 Homo sapiens 14-19 33374784-9 2020 Niacin and butyrate, promising nutrients and unique ligands for the G protein-coupled receptor GPR109A, are reviewed in this paper in detail. Niacin 0-6 hydroxycarboxylic acid receptor 2 Homo sapiens 95-102 31617441-2 2019 Niacin activates the HCAR2 receptor found on adipocytes, macrophages and various immune cells throughout the body. Niacin 0-6 hydroxycarboxylic acid receptor 2 Homo sapiens 21-26 31617441-3 2019 Activation of the HCAR2 receptor by niacin results in beneficial anti-inflammatory effects that are independent of lipid lowering. Niacin 36-42 hydroxycarboxylic acid receptor 2 Homo sapiens 18-23 26932224-10 2016 The GPR109A receptor was discovered a decade ago, leading to a large body of evidence commending the niacin pathway to a lower cardiovascular risk beyond statins. Niacin 101-107 hydroxycarboxylic acid receptor 2 Homo sapiens 4-11 31268250-1 2019 GPR109A (HM74A), a G-protein-coupled receptor, is hypothesized to mediate lipid and lipoprotein changes and dermal flushing associated with niacin administration. Niacin 140-146 hydroxycarboxylic acid receptor 2 Homo sapiens 0-7 31268250-1 2019 GPR109A (HM74A), a G-protein-coupled receptor, is hypothesized to mediate lipid and lipoprotein changes and dermal flushing associated with niacin administration. Niacin 140-146 hydroxycarboxylic acid receptor 2 Homo sapiens 9-14 29759143-3 2018 Here, for the first time, we report that lower dose of niacin in PD patients may affect macrophage polarization from M1 (pro-inflammatory) to M2 (counter-inflammatory) profile through the niacin receptor GPR109A. Niacin 55-61 hydroxycarboxylic acid receptor 2 Homo sapiens 204-211 29473951-5 2018 In ARPE-19 and CCD-841 cells, activation of GPR109A by high concentrations of the agonists 4-HNE (>=10 muM), niacin (>=1000 muM) and 3-OHBA (>=1000 muM) induced apoptosis accompanied by elevated Ca2+ and superoxide levels. Niacin 112-118 hydroxycarboxylic acid receptor 2 Homo sapiens 44-51 30270326-2 2018 HCA2 ligand, niacin, has been used for decades as lipid-modifying drug. Niacin 13-19 hydroxycarboxylic acid receptor 2 Homo sapiens 0-4 28186140-6 2017 Niacin showed a selected additive effect on chemoattractant-induced activation of ERK1/2, JNK and PI3K pathways, but only the MEK inhibitor UO126 reduced niacin-mediated inhibition of macrophage chemotaxis, while activation of ERK1/2 by EGF alone did not inhibit fMLF-mediated migration of HEK293T cells co-expressing HCA2 and fMLF receptor FPR1. Niacin 0-6 hydroxycarboxylic acid receptor 2 Homo sapiens 318-322 28186140-8 2017 Furthermore, niacin rescued mice from septic shock by diminishing inflammatory symptoms and the effect was abrogated in HCA2-/- mice. Niacin 13-19 hydroxycarboxylic acid receptor 2 Homo sapiens 120-124 31273921-0 2019 Nicotinic acid suppresses sebaceous lipogenesis of human sebocytes via activating hydroxycarboxylic acid receptor 2 (HCA2 ). Niacin 0-14 hydroxycarboxylic acid receptor 2 Homo sapiens 82-115 31273921-0 2019 Nicotinic acid suppresses sebaceous lipogenesis of human sebocytes via activating hydroxycarboxylic acid receptor 2 (HCA2 ). Niacin 0-14 hydroxycarboxylic acid receptor 2 Homo sapiens 117-121 31273921-1 2019 Nicotinic acid (NA) activates hydroxycarboxylic acid receptor 2 (HCA2 ), and it is widely used in treating dyslipidaemias. Niacin 0-14 hydroxycarboxylic acid receptor 2 Homo sapiens 30-63 31273921-1 2019 Nicotinic acid (NA) activates hydroxycarboxylic acid receptor 2 (HCA2 ), and it is widely used in treating dyslipidaemias. Niacin 0-14 hydroxycarboxylic acid receptor 2 Homo sapiens 65-69 26932224-11 2016 While mediating niacin"s most prominent adverse effects, GPR109A also seems to mediate anti-lipolytic, anti-inflammatory, and anti-atherogenic effects of niacin. Niacin 154-160 hydroxycarboxylic acid receptor 2 Homo sapiens 57-64 26531288-1 2015 OBJECTIVE: Niacin, activating G-protein coupled receptor (GPR) 109A, stimulates release of vasodilatory prostaglandins (PGs) such as PGE2 which can elicit niacin-associated flushing side effects. Niacin 11-17 hydroxycarboxylic acid receptor 2 Homo sapiens 30-67 26656756-4 2016 In the presence of nicotinic acid the hHCA2 receptor activated almost all G protein pathways except Galphaq (MMY14). Niacin 19-33 hydroxycarboxylic acid receptor 2 Homo sapiens 38-43 26531288-1 2015 OBJECTIVE: Niacin, activating G-protein coupled receptor (GPR) 109A, stimulates release of vasodilatory prostaglandins (PGs) such as PGE2 which can elicit niacin-associated flushing side effects. Niacin 155-161 hydroxycarboxylic acid receptor 2 Homo sapiens 30-67 26273459-0 2015 Low-dose niacin supplementation modulates GPR109A, niacin index and ameliorates Parkinson"s disease symptoms without side effects. Niacin 9-15 hydroxycarboxylic acid receptor 2 Homo sapiens 42-49