PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 12871032-3 2003 The molecular mechanisms of BZs are now well defined in that they enhance the actions of the inhibitory neurotransmitter GABA by binding to a specific recognition site on GABA(A) receptors containing alpha1, alpha2, alpha3 and alpha5 subunits. Benzodiazepines 28-31 adrenoceptor alpha 1D Homo sapiens 200-233 11100148-1 2000 Benzodiazepines (BZs) act on gamma-aminobutyric acid type A (GABAA) receptors such as alpha1beta2gamma2 through key residues within the N-terminal region of alpha subunits, to render their sedative and anxiolytic actions. Benzodiazepines 0-15 adrenoceptor alpha 1D Homo sapiens 86-103 12171574-5 2002 The binding pocket for benzodiazepines is located in a subunit cleft between gamma2 and alpha1 subunits in a position homologous to the agonist binding site for GABA that is located between alpha1 and beta2 subunits. Benzodiazepines 23-38 adrenoceptor alpha 1D Homo sapiens 88-94 11595770-3 2001 The hippocampal formation expresses high levels of alpha subunits with different benzodiazepine binding properties (alpha1, alpha2 and alpha5). Benzodiazepines 81-95 adrenoceptor alpha 1D Homo sapiens 116-122 11306694-7 2001 Benzodiazepine potentiation at alpha3beta3gamma2s with nonselective agonist chlordiazepoxide was greater than at alpha1, alpha2, or alpha5 (P < 0.001). Benzodiazepines 0-14 adrenoceptor alpha 1D Homo sapiens 113-119 11299307-1 2001 L-655,708 is a ligand for the benzodiazepine site of the gamma-aminobutyric acid type A (GABA(A)) receptor that exhibits a 100-fold higher affinity for alpha5-containing receptors compared with alpha1-containing receptors. Benzodiazepines 30-44 adrenoceptor alpha 1D Homo sapiens 194-200 11100148-1 2000 Benzodiazepines (BZs) act on gamma-aminobutyric acid type A (GABAA) receptors such as alpha1beta2gamma2 through key residues within the N-terminal region of alpha subunits, to render their sedative and anxiolytic actions. Benzodiazepines 17-20 adrenoceptor alpha 1D Homo sapiens 86-103 10224099-2 1999 The benzodiazepine binding site was characterized using a site-directed mutagenesis strategy in which amino acids of the alpha5 subunit were substituted by their corresponding alpha1 residues. Benzodiazepines 4-18 adrenoceptor alpha 1D Homo sapiens 176-182 10501225-8 1999 From these observations, it is concluded that the corresponding residues on the alpha1 and beta2 subunits are involved more likely in the gating of the channel by GABA than in the binding of GABA or benzodiazepines. Benzodiazepines 199-214 adrenoceptor alpha 1D Homo sapiens 80-86 9652349-1 1998 The effect of benzodiazepine agonists of varying efficacy on gamma-aminobutyric acidA receptor alpha1 subunit protein expression was determined in primary cultured cerebellar granule cells. Benzodiazepines 14-28 adrenoceptor alpha 1D Homo sapiens 95-101 9754930-0 1998 Amino acid residue 200 on the alpha1 subunit of GABA(A) receptors affects the interaction with selected benzodiazepine binding site ligands. Benzodiazepines 104-118 adrenoceptor alpha 1D Homo sapiens 30-36 9652349-3 1998 The grading of effect of the benzodiazepine partial agonists on alpha1 subunit protein expression is consistent with their agonist efficacies. Benzodiazepines 29-43 adrenoceptor alpha 1D Homo sapiens 64-70 7780638-5 1995 DMCM at low concentrations (< 0.5 microM) occupying only the benzodiazepine site decreased GABA-induced Cl currents in the alpha 1 beta 2 gamma 2 and alpha 3 beta 2 gamma 2 subtypes as expected from an inverse agonist, but produced no change in the alpha 6 beta 2 gamma 2 subtype (perhaps a neutral antagonist). Benzodiazepines 64-78 adrenoceptor alpha 1D Homo sapiens 126-148 8723715-8 1996 The distributional patterns obtained for the alpha 1 and alpha 2 subunits suggest that striatal efferent neurons directly influence pallidal neurons displaying a distinct GABAA subunit composition, which may be of pharmacological importance since the alpha 1 beta x gamma 2-subunits containing receptors have mainly a benzodiazepine type I pharmacology. Benzodiazepines 318-332 adrenoceptor alpha 1D Homo sapiens 45-64 8723715-8 1996 The distributional patterns obtained for the alpha 1 and alpha 2 subunits suggest that striatal efferent neurons directly influence pallidal neurons displaying a distinct GABAA subunit composition, which may be of pharmacological importance since the alpha 1 beta x gamma 2-subunits containing receptors have mainly a benzodiazepine type I pharmacology. Benzodiazepines 318-332 adrenoceptor alpha 1D Homo sapiens 45-52 8592140-0 1996 The alpha 1 and alpha 6 subunits can coexist in the same cerebellar GABAA receptor maintaining their individual benzodiazepine-binding specificities. Benzodiazepines 112-126 adrenoceptor alpha 1D Homo sapiens 4-23 8592140-1 1996 Two GABAA receptor subunit-specific antibodies anti-alpha 6 and anti-alpha 1 have been used for elucidating the relationship between the presence of alpha 1 and/or alpha 6 subunits in the cerebellar GABAA receptors and the benzodiazepine-binding specificity. Benzodiazepines 223-237 adrenoceptor alpha 1D Homo sapiens 69-76 8592140-1 1996 Two GABAA receptor subunit-specific antibodies anti-alpha 6 and anti-alpha 1 have been used for elucidating the relationship between the presence of alpha 1 and/or alpha 6 subunits in the cerebellar GABAA receptors and the benzodiazepine-binding specificity. Benzodiazepines 223-237 adrenoceptor alpha 1D Homo sapiens 149-171 8592140-5 1996 The results also show that receptors where alpha 1 and alpha 6 subunits coexist have two pharmacologically different benzodiazepine-binding properties, each associated with a different alpha subunit. Benzodiazepines 117-131 adrenoceptor alpha 1D Homo sapiens 43-62 30210295-5 2018 Herein, we investigated the effect of a BDZ (flurazepam) on the spontaneous and GABA-induced activity for wild-type (WT, alpha1beta2gamma2) and mutated (at the orthosteric binding site alpha1F64) GABAARs. Benzodiazepines 40-43 adrenoceptor alpha 1D Homo sapiens 121-138 7799410-4 1994 Notably, the alpha 1 and alpha 6 variants confer high and low affinity for BZ agonists to the resulting receptor subtype, respectively. Benzodiazepines 75-77 adrenoceptor alpha 1D Homo sapiens 13-32 8242240-2 1993 In this study, we compared two series of newly discovered ligands for their selectivity to benzodiazepine sites in the alpha 1 beta 2 gamma 2 and the alpha 6 beta 2 gamma 2 subtypes of cloned gamma-aminobutyric acidA (GABAA) receptors, the latter being unique in not interacting with classical benzodiazepines. Benzodiazepines 91-105 adrenoceptor alpha 1D Homo sapiens 119-141 8242240-10 1993 We propose that the benzodiazepine site of the alpha 6 beta 2 gamma 2 subtype shares overlapping regions with that of the alpha 1 beta 2 gamma 2 subtype, but has a sterically restricted out-of-plane region, which may be also incompatible with the 5-phenyl group of classical benzodiazepines. Benzodiazepines 20-34 adrenoceptor alpha 1D Homo sapiens 122-144 8391122-0 1993 Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors. Benzodiazepines 132-146 adrenoceptor alpha 1D Homo sapiens 175-182 1346133-5 1992 Notably, the alpha 1 and alpha 6 variants impart on alpha chi beta 2 gamma 2 receptors high and negligible affinity, respectively, to BZ ligands with sedative as well as anxiolytic activities. Benzodiazepines 134-136 adrenoceptor alpha 1D Homo sapiens 13-32 1346133-7 1992 Furthermore, we identify a single histidine residue in the alpha 1 variant, replaced by an arginine in alpha 6, as a major determinant for high affinity binding of BZ agonists. Benzodiazepines 164-166 adrenoceptor alpha 1D Homo sapiens 59-66 1346133-9 1992 Hence, this histidine present in the alpha 1, alpha 2, alpha 3, and alpha 5 subunits appears to be a key residue for the action of clinically used BZ ligands. Benzodiazepines 147-149 adrenoceptor alpha 1D Homo sapiens 37-44 1665550-1 1991 We compared the modulation of GABA (gamma-aminobutyric acid)-activated currents by benzodiazepines in recombinant GABAA receptors containing either one of two alpha subunits, alpha 1 or alpha 6. Benzodiazepines 83-98 adrenoceptor alpha 1D Homo sapiens 175-193 1664058-5 1991 Partial sequencing of proteolytic fragments of these polypeptides yielded sequences found in all alpha clones, and identified the benzodiazepine binding site within residues 8-297 and probably between 106-297 of alpha 1; the 44 kDa and 31 kDa bands yielded fragments containing alpha 3 sequence. Benzodiazepines 130-144 adrenoceptor alpha 1D Homo sapiens 212-219 7901754-0 1993 Potentiation of gamma-aminobutyric acid-induced chloride currents by various benzodiazepine site agonists with the alpha 1 gamma 2, beta 2 gamma 2 and alpha 1 beta 2 gamma 2 subtypes of cloned gamma-aminobutyric acid type A receptors. Benzodiazepines 77-91 adrenoceptor alpha 1D Homo sapiens 115-173 7901754-1 1993 Previous studies with cloned gamma-aminobutyric acid type A receptors expressed in human embryonic kidney cells have indicated that the alpha 1 beta 2 gamma 2 and alpha 1 gamma 2 (but not alpha 1 beta 2) subtypes have benzodiazepine sites. Benzodiazepines 218-232 adrenoceptor alpha 1D Homo sapiens 136-143 7901754-1 1993 Previous studies with cloned gamma-aminobutyric acid type A receptors expressed in human embryonic kidney cells have indicated that the alpha 1 beta 2 gamma 2 and alpha 1 gamma 2 (but not alpha 1 beta 2) subtypes have benzodiazepine sites. Benzodiazepines 218-232 adrenoceptor alpha 1D Homo sapiens 163-170 7901754-1 1993 Previous studies with cloned gamma-aminobutyric acid type A receptors expressed in human embryonic kidney cells have indicated that the alpha 1 beta 2 gamma 2 and alpha 1 gamma 2 (but not alpha 1 beta 2) subtypes have benzodiazepine sites. Benzodiazepines 218-232 adrenoceptor alpha 1D Homo sapiens 163-170 7901754-7 1993 These data indicate that, in the presence of gamma 2, beta 2 may substitute for alpha 1 in forming the benzodiazepine site of limited sensitivity to the type 1 ligands. Benzodiazepines 103-117 adrenoceptor alpha 1D Homo sapiens 80-87 7901754-8 1993 It appears that individual ligands for benzodiazepine sites have their own sets of interacting domains, which are distributed in alpha 1 and gamma 2, and the agonistic activity of type 1 ligands may be more dependent on the alpha 1-specific domains than is that of less selective ligands. Benzodiazepines 39-53 adrenoceptor alpha 1D Homo sapiens 129-148 7901754-8 1993 It appears that individual ligands for benzodiazepine sites have their own sets of interacting domains, which are distributed in alpha 1 and gamma 2, and the agonistic activity of type 1 ligands may be more dependent on the alpha 1-specific domains than is that of less selective ligands. Benzodiazepines 39-53 adrenoceptor alpha 1D Homo sapiens 129-136 1321437-6 1992 Additionally, the recombinant receptors have the same benzodiazepine pharmacology as native alpha 1-containing GABAA receptors and function as GABA-gated chloride channels. Benzodiazepines 54-68 adrenoceptor alpha 1D Homo sapiens 92-99 24241181-4 2013 The structures of ten benzodiazepine type drugs and two non-benzodiazepine type drugs were then docked into the potential benzodiazepine binding site on the GABA(A)R. By analyzing the docking results, the critical residues His102 (alpha1), Phe77 (gamma2) and Phe100 (alpha1) were identified in the binding site. Benzodiazepines 22-36 adrenoceptor alpha 1D Homo sapiens 231-237 29138471-2 2017 The binding sites for the agonist GABA are located at the beta2+/alpha1- subunit interfaces and the modulatory site for benzodiazepines at alpha1+/gamma2-. Benzodiazepines 120-135 adrenoceptor alpha 1D Homo sapiens 139-145 29138471-5 2017 Point mutations were introduced in beta2 or gamma2 subunits at positions homologous to alpha1- benzodiazepine binding and GABA binding positions, respectively. Benzodiazepines 95-109 adrenoceptor alpha 1D Homo sapiens 87-93 29872302-4 2018 Recent findings have highlighted the importance of alpha1 containing GABAA receptors in the mechanisms of addiction and tolerance in benzodiazepine treatments. Benzodiazepines 133-147 adrenoceptor alpha 1D Homo sapiens 51-57 28445782-3 2017 The alpha1-, beta2,3- and gamma2- subunits which combine to form a benzodiazepine sensitive GABAA receptor showed the most intense levels of staining and were the most common subunits found throughout the human thalamus especially in the ventral and posterior nuclear groups. Benzodiazepines 67-81 adrenoceptor alpha 1D Homo sapiens 4-10 23088350-6 2014 Regression models were used to determine the amount of variance in success in improving functional walking level, gains in walking speed, and declines in lower extremity, upper extremity, and cognitive impairment accounted for by alpha1 noradrenergic blockers + alpha2 noradrenergic agonists, benzodiazepines, voltage-sensitive sodium channel anticonvulsants, and alpha2delta voltage-sensitive calcium channel blockers. Benzodiazepines 293-308 adrenoceptor alpha 1D Homo sapiens 230-236 24241181-4 2013 The structures of ten benzodiazepine type drugs and two non-benzodiazepine type drugs were then docked into the potential benzodiazepine binding site on the GABA(A)R. By analyzing the docking results, the critical residues His102 (alpha1), Phe77 (gamma2) and Phe100 (alpha1) were identified in the binding site. Benzodiazepines 22-36 adrenoceptor alpha 1D Homo sapiens 267-273 24241181-4 2013 The structures of ten benzodiazepine type drugs and two non-benzodiazepine type drugs were then docked into the potential benzodiazepine binding site on the GABA(A)R. By analyzing the docking results, the critical residues His102 (alpha1), Phe77 (gamma2) and Phe100 (alpha1) were identified in the binding site. Benzodiazepines 60-74 adrenoceptor alpha 1D Homo sapiens 231-237 24241181-4 2013 The structures of ten benzodiazepine type drugs and two non-benzodiazepine type drugs were then docked into the potential benzodiazepine binding site on the GABA(A)R. By analyzing the docking results, the critical residues His102 (alpha1), Phe77 (gamma2) and Phe100 (alpha1) were identified in the binding site. Benzodiazepines 60-74 adrenoceptor alpha 1D Homo sapiens 231-237 21309116-1 2010 Nonselective benzodiazepines exert their pharmacological effects via GABAA receptors containing either an alpha1, alpha2, alpha3, or alpha5 subunit. Benzodiazepines 13-28 adrenoceptor alpha 1D Homo sapiens 106-112 20417252-9 2010 Our data suggest a species difference in the expression profiles of the alpha1 and gamma2 subunits in the locus coeruleus, with the sedation-related benzodiazepine sites being more important in man than rodents. Benzodiazepines 149-163 adrenoceptor alpha 1D Homo sapiens 72-89 15926867-1 2005 Non-selective benzodiazepine (BZ) binding-site full agonists, exemplified by diazepam, act by enhancing the inhibitory effects of GABA at GABA(A) receptors containing either an alpha1, -2, -3 or -5 subunit. Benzodiazepines 14-28 adrenoceptor alpha 1D Homo sapiens 177-197 19300612-2 2007 Like other non-benzodiazepine hypnotics, its mechanism of action is to modulate subunits, especially the alpha-1 subunit, of the GABA receptor complex in order to induce sedation. Benzodiazepines 15-29 adrenoceptor alpha 1D Homo sapiens 105-112 17953656-6 2007 The homologous residues to alpha(5) H105 in alpha(1) , alpha(2) , and alpha(3) are well-known determinants of the action of classical benzodiazepines. Benzodiazepines 134-149 adrenoceptor alpha 1D Homo sapiens 44-51 17953656-7 2007 Other studies have shown that replacement of these histidines alpha(1) H101, alpha(2) H101, and alpha(3) H126 by arginine, as naturally present in alpha(4) and alpha(6) , leads to benzodiazepine insensitivity of these receptors. Benzodiazepines 180-194 adrenoceptor alpha 1D Homo sapiens 62-69 17539703-9 2007 Receptors containing the alpha1, alpha2, or alpha3 subunits with gamma2 are usually found at synapses and are sensitive to benzodiazepines and zolpidem, whereas alpha4 and alpha6 subunits are often found with delta and play a role in extrasynaptic receptors (in thalamus and dentate), as does the alpha5 subunit (in CA1). Benzodiazepines 123-138 adrenoceptor alpha 1D Homo sapiens 25-39 15926867-1 2005 Non-selective benzodiazepine (BZ) binding-site full agonists, exemplified by diazepam, act by enhancing the inhibitory effects of GABA at GABA(A) receptors containing either an alpha1, -2, -3 or -5 subunit. Benzodiazepines 30-32 adrenoceptor alpha 1D Homo sapiens 177-197 15125950-2 2004 These compounds have consistently higher binding affinity for the GABAA alpha5 receptor subtype over the other benzodiazepine-sensitive GABAA receptor subtypes (alpha1, alpha2 and alpha3). Benzodiazepines 111-125 adrenoceptor alpha 1D Homo sapiens 161-167 15505688-2 2004 Molecular studies have shown that binding benzodiazepines to GABAA receptors containing the Alpha1 subunit mediates the sedative properties of benzodiazepines. Benzodiazepines 42-57 adrenoceptor alpha 1D Homo sapiens 92-98 15505688-2 2004 Molecular studies have shown that binding benzodiazepines to GABAA receptors containing the Alpha1 subunit mediates the sedative properties of benzodiazepines. Benzodiazepines 143-158 adrenoceptor alpha 1D Homo sapiens 92-98 14573876-6 2003 In addition, the benzodiazepine (BZ)-binding affinity of the recombinant fragments were measured using fluorescence polarization to be 2.16 microM, 3.63 microM, and 1.34 microM for the alpha(1), beta(2), and gamma(2) subunit fragments, respectively, indicating that all three homomeric assemblies, including that of the beta(2) subunit, generally not associated with BZ binding, can bind BZ in the micromolar range. Benzodiazepines 17-31 adrenoceptor alpha 1D Homo sapiens 185-193 14573876-6 2003 In addition, the benzodiazepine (BZ)-binding affinity of the recombinant fragments were measured using fluorescence polarization to be 2.16 microM, 3.63 microM, and 1.34 microM for the alpha(1), beta(2), and gamma(2) subunit fragments, respectively, indicating that all three homomeric assemblies, including that of the beta(2) subunit, generally not associated with BZ binding, can bind BZ in the micromolar range. Benzodiazepines 33-35 adrenoceptor alpha 1D Homo sapiens 185-193 14573876-6 2003 In addition, the benzodiazepine (BZ)-binding affinity of the recombinant fragments were measured using fluorescence polarization to be 2.16 microM, 3.63 microM, and 1.34 microM for the alpha(1), beta(2), and gamma(2) subunit fragments, respectively, indicating that all three homomeric assemblies, including that of the beta(2) subunit, generally not associated with BZ binding, can bind BZ in the micromolar range. Benzodiazepines 367-369 adrenoceptor alpha 1D Homo sapiens 185-193 14573876-6 2003 In addition, the benzodiazepine (BZ)-binding affinity of the recombinant fragments were measured using fluorescence polarization to be 2.16 microM, 3.63 microM, and 1.34 microM for the alpha(1), beta(2), and gamma(2) subunit fragments, respectively, indicating that all three homomeric assemblies, including that of the beta(2) subunit, generally not associated with BZ binding, can bind BZ in the micromolar range. Benzodiazepines 367-369 adrenoceptor alpha 1D Homo sapiens 185-193