Pub Date : 2023-04-26DOI: 10.2218/gtopdb/f29/2023.1
Dominique Bataille, Susan L. Chan, Philippe Delagrange, Daniel J. Drucker, Burkhard Göke, Rebecca Hills, Kelly E. Mayo, Laurence J. Miller, Roberto Salvatori, Bernard Thorens
The glucagon family of receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on the Glucagon receptor family [165]) are activated by the endogenous peptide (27-44 aa) hormones glucagon, glucagon-like peptide 1, glucagon-like peptide 2, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory polypeptide), GHRH and secretin. One common precursor (GCG) generates glucagon, glucagon-like peptide 1 and glucagon-like peptide 2 peptides [121]. For a recent review on the current understanding of the structures of GLP-1 and GLP-1R, the molecular basis of their interaction, and the associated signaling events see de Graaf et al., 2016 [90].
胰高血糖素受体家族(由NC-IUPHAR胰高血糖素受体家族小组委员会商定的命名[165])由内源性肽(27-44 aa)激素胰高血糖素、胰高血糖素样肽1、胰高血糖素样肽2、葡萄糖依赖性胰岛素性多肽(也称为胃抑制多肽)、GHRH和分泌素激活。一种常见的前体(GCG)产生胰高血糖素、胰高血糖素样肽1和胰高血糖素样肽2肽[121]。关于GLP-1和GLP-1R的结构、它们相互作用的分子基础以及相关信号事件的最新综述见de Graaf et al.， 2016[90]。
{"title":"Glucagon receptor family in GtoPdb v.2023.1","authors":"Dominique Bataille, Susan L. Chan, Philippe Delagrange, Daniel J. Drucker, Burkhard Göke, Rebecca Hills, Kelly E. Mayo, Laurence J. Miller, Roberto Salvatori, Bernard Thorens","doi":"10.2218/gtopdb/f29/2023.1","DOIUrl":"https://doi.org/10.2218/gtopdb/f29/2023.1","url":null,"abstract":"The glucagon family of receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on the Glucagon receptor family [165]) are activated by the endogenous peptide (27-44 aa) hormones glucagon, glucagon-like peptide 1, glucagon-like peptide 2, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory polypeptide), GHRH and secretin. One common precursor (GCG) generates glucagon, glucagon-like peptide 1 and glucagon-like peptide 2 peptides [121]. For a recent review on the current understanding of the structures of GLP-1 and GLP-1R, the molecular basis of their interaction, and the associated signaling events see de Graaf et al., 2016 [90].","PeriodicalId":14617,"journal":{"name":"IUPHAR/BPS Guide to Pharmacology CITE","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135017424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-26DOI: 10.2218/gtopdb/f69/2023.1
Richard Aldrich, K. George Chandy, Stephan Grissmer, George A. Gutman, Leonard K. Kaczmarek, Aguan D. Wei, Heike Wulff
Calcium- and sodium- activated potassium channels are members of the 6TM family of K channels which comprises the voltage-gated KV subfamilies, including the KCNQ subfamily, the EAG subfamily (which includes hERG channels), the Ca2+-activated Slo subfamily (actually with 6 or 7TM) and the Ca2+- and Na+-activated SK subfamily (nomenclature as agreed by the NC-IUPHAR Subcommittee on Calcium- and sodium-activated potassium channels [126]). As for the 2TM family, the pore-forming a subunits form tetramers and heteromeric channels may be formed within subfamilies (e.g. KV1.1 with KV1.2; KCNQ2 with KCNQ3).
{"title":"Calcium- and sodium-activated potassium channels (K<sub>Ca</sub>, K<sub>Na</sub>) in GtoPdb v.2023.1","authors":"Richard Aldrich, K. George Chandy, Stephan Grissmer, George A. Gutman, Leonard K. Kaczmarek, Aguan D. Wei, Heike Wulff","doi":"10.2218/gtopdb/f69/2023.1","DOIUrl":"https://doi.org/10.2218/gtopdb/f69/2023.1","url":null,"abstract":"Calcium- and sodium- activated potassium channels are members of the 6TM family of K channels which comprises the voltage-gated KV subfamilies, including the KCNQ subfamily, the EAG subfamily (which includes hERG channels), the Ca2+-activated Slo subfamily (actually with 6 or 7TM) and the Ca2+- and Na+-activated SK subfamily (nomenclature as agreed by the NC-IUPHAR Subcommittee on Calcium- and sodium-activated potassium channels [126]). As for the 2TM family, the pore-forming a subunits form tetramers and heteromeric channels may be formed within subfamilies (e.g. KV1.1 with KV1.2; KCNQ2 with KCNQ3).","PeriodicalId":14617,"journal":{"name":"IUPHAR/BPS Guide to Pharmacology CITE","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135018442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-26DOI: 10.2218/gtopdb/f260/2023.1
Chen Yan
3',5'-Cyclic nucleotide phosphodiesterases (PDEs, 3',5'-cyclic-nucleotide 5'-nucleotidohydrolase), E.C. 3.1.4.17, catalyse the hydrolysis of a 3',5'-cyclic nucleotide (usually cyclic AMP or cyclic GMP). isobutylmethylxanthine is a nonselective inhibitor with an IC50 value in the millimolar range for all isoforms except PDE 8A, 8B and 9A. A 2',3'-cyclic nucleotide 3'-phosphodiesterase (E.C. 3.1.4.37 CNPase) activity is associated with myelin formation in the development of the CNS.
{"title":"Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs) in GtoPdb v.2023.1","authors":"Chen Yan","doi":"10.2218/gtopdb/f260/2023.1","DOIUrl":"https://doi.org/10.2218/gtopdb/f260/2023.1","url":null,"abstract":"3',5'-Cyclic nucleotide phosphodiesterases (PDEs, 3',5'-cyclic-nucleotide 5'-nucleotidohydrolase), E.C. 3.1.4.17, catalyse the hydrolysis of a 3',5'-cyclic nucleotide (usually cyclic AMP or cyclic GMP). isobutylmethylxanthine is a nonselective inhibitor with an IC50 value in the millimolar range for all isoforms except PDE 8A, 8B and 9A. A 2',3'-cyclic nucleotide 3'-phosphodiesterase (E.C. 3.1.4.37 CNPase) activity is associated with myelin formation in the development of the CNS.","PeriodicalId":14617,"journal":{"name":"IUPHAR/BPS Guide to Pharmacology CITE","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135018443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-26DOI: 10.2218/gtopdb/f71/2023.1
Elvir Becirovic, Martin Biel, Stefanie Fenske, Verena Hammelmann, Franz Hofmann, U. Benjamin Kaupp
Cyclic nucleotide-gated (CNG) channels are responsible for signalling in the primary sensory cells of the vertebrate visual and olfactory systems. CNG channels are voltage-independent cation channels formed as tetramers. Each subunit has 6TM, with the pore-forming domain between TM5 and TM6. CNG channels were first found in rod photoreceptors [83, 120], where light signals through rhodopsin and transducin to stimulate phosphodiesterase and reduce intracellular cyclic GMP level. This results in a closure of CNG channels and a reduced ‘dark current’. Similar channels were found in the cilia of olfactory neurons [181] and the pineal gland [71]. The cyclic nucleotides bind to a domain in the C terminus of the subunit protein: other channels directly binding cyclic nucleotides include hyperolarisation-activated, cyclic nucleotide-gated channels (HCN), ether-a-go-go and certain plant potassium channels.The HCN channels are cation channels that are activated by hyperpolarisation at voltages negative to ~-50 mV. The cyclic nucleotides cyclic AMP and cyclic GMP directly bind to the cyclic nucleotide-binding domain of HCN channels and shift their activation curves to more positive voltages, thereby enhancing channel activity. HCN channels underlie pacemaker currents found in many excitable cells including cardiac cells and neurons [65, 192]. In native cells, these currents have a variety of names, such as Ih, Iq and If. The four known HCN channels have six transmembrane domains and form tetramers. It is believed that the channels can form heteromers with each other, as has been shown for HCN1 and HCN4 [2]. High resolution structural studies of CNG and HCN channels has provided insight into the the gating processes of these channels [139, 146, 140]. A standardised nomenclature for CNG and HCN channels has been proposed by the NC-IUPHAR Subcommittee on voltage-gated ion channels [108].
{"title":"Cyclic nucleotide-regulated channels (CNG) in GtoPdb v.2023.1","authors":"Elvir Becirovic, Martin Biel, Stefanie Fenske, Verena Hammelmann, Franz Hofmann, U. Benjamin Kaupp","doi":"10.2218/gtopdb/f71/2023.1","DOIUrl":"https://doi.org/10.2218/gtopdb/f71/2023.1","url":null,"abstract":"Cyclic nucleotide-gated (CNG) channels are responsible for signalling in the primary sensory cells of the vertebrate visual and olfactory systems. CNG channels are voltage-independent cation channels formed as tetramers. Each subunit has 6TM, with the pore-forming domain between TM5 and TM6. CNG channels were first found in rod photoreceptors [83, 120], where light signals through rhodopsin and transducin to stimulate phosphodiesterase and reduce intracellular cyclic GMP level. This results in a closure of CNG channels and a reduced ‘dark current’. Similar channels were found in the cilia of olfactory neurons [181] and the pineal gland [71]. The cyclic nucleotides bind to a domain in the C terminus of the subunit protein: other channels directly binding cyclic nucleotides include hyperolarisation-activated, cyclic nucleotide-gated channels (HCN), ether-a-go-go and certain plant potassium channels.The HCN channels are cation channels that are activated by hyperpolarisation at voltages negative to ~-50 mV. The cyclic nucleotides cyclic AMP and cyclic GMP directly bind to the cyclic nucleotide-binding domain of HCN channels and shift their activation curves to more positive voltages, thereby enhancing channel activity. HCN channels underlie pacemaker currents found in many excitable cells including cardiac cells and neurons [65, 192]. In native cells, these currents have a variety of names, such as Ih, Iq and If. The four known HCN channels have six transmembrane domains and form tetramers. It is believed that the channels can form heteromers with each other, as has been shown for HCN1 and HCN4 [2]. High resolution structural studies of CNG and HCN channels has provided insight into the the gating processes of these channels [139, 146, 140]. A standardised nomenclature for CNG and HCN channels has been proposed by the NC-IUPHAR Subcommittee on voltage-gated ion channels [108].","PeriodicalId":14617,"journal":{"name":"IUPHAR/BPS Guide to Pharmacology CITE","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135018446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-26DOI: 10.2218/gtopdb/f53/2023.1
Alessandro Bisello, Michael Chorev, Peter A. Friedman, Tom Gardella, Rebecca Hills, Harald Jueppner, T. John Martin, Robert A. Nissenson, John Thomas Potts, Jr., Caroline Silve, Ted B. Usdin, Jean-Pierre Vilardaga
The parathyroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Parathyroid Hormone Receptors [50]) are class B G protein-coupled receptors. The parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1 receptor) is activated by precursor-derived peptides: PTH (84 amino acids), and PTHrP (141 amino-acids) and related peptides (PTH-(1-34), PTHrP-(1-36)). The parathyroid hormone 2 receptor (PTH2 receptor) is activated by the precursor-derived peptide TIP39 (39 amino acids). [125I]PTH may be used to label both PTH1 and PTH2 receptors. The structure of a long-active PTH analogue (LA-PTH, an hybrid of PTH-(1-13) and PTHrP-(14-36)) bound to the PTH1 receptor-Gs complex has been resolved by cryo-electron microscopy [148]. Another structure of a PTH-(1-34) analog bound to a thermostabilized inactive PTH1 receptor has been obtained with X-ray crytallography [35].
{"title":"Parathyroid hormone receptors in GtoPdb v.2023.1","authors":"Alessandro Bisello, Michael Chorev, Peter A. Friedman, Tom Gardella, Rebecca Hills, Harald Jueppner, T. John Martin, Robert A. Nissenson, John Thomas Potts, Jr., Caroline Silve, Ted B. Usdin, Jean-Pierre Vilardaga","doi":"10.2218/gtopdb/f53/2023.1","DOIUrl":"https://doi.org/10.2218/gtopdb/f53/2023.1","url":null,"abstract":"The parathyroid hormone receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Parathyroid Hormone Receptors [50]) are class B G protein-coupled receptors. The parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1 receptor) is activated by precursor-derived peptides: PTH (84 amino acids), and PTHrP (141 amino-acids) and related peptides (PTH-(1-34), PTHrP-(1-36)). The parathyroid hormone 2 receptor (PTH2 receptor) is activated by the precursor-derived peptide TIP39 (39 amino acids). [125I]PTH may be used to label both PTH1 and PTH2 receptors. The structure of a long-active PTH analogue (LA-PTH, an hybrid of PTH-(1-13) and PTHrP-(14-36)) bound to the PTH1 receptor-Gs complex has been resolved by cryo-electron microscopy [148]. Another structure of a PTH-(1-34) analog bound to a thermostabilized inactive PTH1 receptor has been obtained with X-ray crytallography [35].","PeriodicalId":14617,"journal":{"name":"IUPHAR/BPS Guide to Pharmacology CITE","volume":"55 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135018450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-26DOI: 10.2218/gtopdb/f31/2023.1
L. Heitman, A. IJzerman, C. McArdle, Adam J Pawson
GnRH1 and GnRH2 receptors (provisonal nomenclature [39], also called Type I and Type II GnRH receptor, respectively [85]) have been cloned from numerous species, most of which express two or three types of GnRH receptor [85, 84, 114]. GnRH I (p-Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) is a hypothalamic decapeptide also known as luteinizing hormone-releasing hormone, gonadoliberin, luliberin, gonadorelin or simply as GnRH. It is a member of a family of similar peptides found in many species [85, 84, 114] including GnRH II (pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2 (which is also known as chicken GnRH-II). Receptors for three forms of GnRH exist in some species but only GnRH I and GnRH II and their cognate receptors have been found in mammals [85, 84, 114]. GnRH1 receptors are expressed by pituitary gonadotrophs, where they mediate the effects of GnRH on gonadotropin hormone synthesis and secretion that underpin central control of mammalian reproduction. GnRH analogues are used in assisted reproduction and to treat steroid hormone-dependent conditions [58]. Notably, agonists cause desensitization of GnRH-stimulated gonadotropin secretion and the consequent reduction in circulating sex steroids is exploited to treat hormone-dependent cancers of the breast, ovary and prostate [58]. GnRH1 receptors are selectively activated by GnRH I and all lack the COOH-terminal tails found in other GPCRs. GnRH2 receptors do have COOH-terminal tails and (where tested) are selective for GnRH II over GnRH I. GnRH2 receptors are expressed by some primates but not by humans [88]. Phylogenetic classifications divide GnRH receptors into three [85] or five groups [130] and highlight examples of gene loss through evolution, with humans retaining only one ancient gene. The structure of the GnRH1 receptor in complex with elagolix has been elucidated [133].
GnRH1和GnRH2受体(暂定命名法[39]，也分别称为I型和II型GnRH受体[85])已经从许多物种中克隆出来，其中大多数表达两种或三种GnRH受体[85,84,114]。GnRH I (p-Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2)是一种下丘脑十肽，也被称为促黄体激素释放激素、促性腺激素、促性腺激素、促性腺激素或简称GnRH。它是许多物种中发现的类似肽家族的成员[85,84,114]，包括GnRH II (pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2(也称为鸡GnRH-II)。在一些物种中存在三种形式的GnRH受体，但在哺乳动物中只发现了GnRH I和GnRH II及其同源受体[85,84,114]。GnRH1受体由垂体促性腺激素表达，介导GnRH对促性腺激素的合成和分泌的影响，而促性腺激素是哺乳动物生殖的中枢控制。GnRH类似物用于辅助生殖和治疗类固醇激素依赖性疾病[58]。值得注意的是，激动剂会导致gnrh刺激的促性腺激素分泌脱敏，因此循环性类固醇的减少被用于治疗激素依赖性的乳腺癌、卵巢癌和前列腺癌[58]。GnRH1受体被GnRH I选择性激活，并且都缺乏其他gpcr中发现的cooh末端尾部。GnRH2受体确实具有cooh末端尾巴，并且(在测试中)对GnRH II而不是GnRH i具有选择性。GnRH2受体在一些灵长类动物中表达，但在人类中不表达[88]。系统发育分类将GnRH受体分为三组[85]或五组[130]，并强调了基因在进化中丢失的例子，人类只保留了一个古老的基因。GnRH1受体与elagolix复合物的结构已被阐明[133]。
{"title":"Gonadotrophin-releasing hormone receptors in GtoPdb v.2023.1","authors":"L. Heitman, A. IJzerman, C. McArdle, Adam J Pawson","doi":"10.2218/gtopdb/f31/2023.1","DOIUrl":"https://doi.org/10.2218/gtopdb/f31/2023.1","url":null,"abstract":"GnRH1 and GnRH2 receptors (provisonal nomenclature [39], also called Type I and Type II GnRH receptor, respectively [85]) have been cloned from numerous species, most of which express two or three types of GnRH receptor [85, 84, 114]. GnRH I (p-Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) is a hypothalamic decapeptide also known as luteinizing hormone-releasing hormone, gonadoliberin, luliberin, gonadorelin or simply as GnRH. It is a member of a family of similar peptides found in many species [85, 84, 114] including GnRH II (pGlu-His-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH2 (which is also known as chicken GnRH-II). Receptors for three forms of GnRH exist in some species but only GnRH I and GnRH II and their cognate receptors have been found in mammals [85, 84, 114]. GnRH1 receptors are expressed by pituitary gonadotrophs, where they mediate the effects of GnRH on gonadotropin hormone synthesis and secretion that underpin central control of mammalian reproduction. GnRH analogues are used in assisted reproduction and to treat steroid hormone-dependent conditions [58]. Notably, agonists cause desensitization of GnRH-stimulated gonadotropin secretion and the consequent reduction in circulating sex steroids is exploited to treat hormone-dependent cancers of the breast, ovary and prostate [58]. GnRH1 receptors are selectively activated by GnRH I and all lack the COOH-terminal tails found in other GPCRs. GnRH2 receptors do have COOH-terminal tails and (where tested) are selective for GnRH II over GnRH I. GnRH2 receptors are expressed by some primates but not by humans [88]. Phylogenetic classifications divide GnRH receptors into three [85] or five groups [130] and highlight examples of gene loss through evolution, with humans retaining only one ancient gene. The structure of the GnRH1 receptor in complex with elagolix has been elucidated [133].","PeriodicalId":14617,"journal":{"name":"IUPHAR/BPS Guide to Pharmacology CITE","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80331581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-26DOI: 10.2218/gtopdb/f6/2023.1
Wayne Alexander, K. Bernstein, K. Catt, M. de Gasparo, Khuraijam Dhanachandra Singh, S. Eguchi, E. Escher, T. Goodfriend, M. Horiuchi, L. Hunyady, A. Husain, T. Inagami, S. Karnik, Jacqueline R. Kemp, W. Thomas, P. Timmermans, Kalyan C. Tirupula, Hamiyet Unal, T. Unger, P. Vanderheyden
The actions of angiotensin II (Ang II) are mediated by AT1 and AT2 receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Angiotensin receptors [63, 155]), which have around 30% sequence similarity. The decapeptide angiotensin I, the octapeptide angiotensin II and the heptapeptide angiotensin III are endogenous ligands. losartan, candesartan, olmesartan, telmisartan, etc. are clinically used AT1 receptor blockers.
{"title":"Angiotensin receptors in GtoPdb v.2023.1","authors":"Wayne Alexander, K. Bernstein, K. Catt, M. de Gasparo, Khuraijam Dhanachandra Singh, S. Eguchi, E. Escher, T. Goodfriend, M. Horiuchi, L. Hunyady, A. Husain, T. Inagami, S. Karnik, Jacqueline R. Kemp, W. Thomas, P. Timmermans, Kalyan C. Tirupula, Hamiyet Unal, T. Unger, P. Vanderheyden","doi":"10.2218/gtopdb/f6/2023.1","DOIUrl":"https://doi.org/10.2218/gtopdb/f6/2023.1","url":null,"abstract":"The actions of angiotensin II (Ang II) are mediated by AT1 and AT2 receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Angiotensin receptors [63, 155]), which have around 30% sequence similarity. The decapeptide angiotensin I, the octapeptide angiotensin II and the heptapeptide angiotensin III are endogenous ligands. losartan, candesartan, olmesartan, telmisartan, etc. are clinically used AT1 receptor blockers.","PeriodicalId":14617,"journal":{"name":"IUPHAR/BPS Guide to Pharmacology CITE","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82020477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-26DOI: 10.2218/gtopdb/f30/2023.1
S. Costagliola, J. Dias, M. Gershengorn, Adam J. Pawson, D. Segaloff, A. Themmen, G. Vassart
Glycoprotein hormone receptors (provisional nomenclature [47]) are activated by a non-covalent heterodimeric glycoprotein made up of a common α chain (glycoprotein hormone common alpha subunit CGA, P01215), with a unique β chain that confers the biological specificity to FSH, LH, hCG or TSH. There is binding cross-reactivity across the endogenous agonists for each of the glycoprotein hormone receptors. The deglycosylated hormones appear to exhibit reduced efficacy at these receptors [122, 31].
{"title":"Glycoprotein hormone receptors in GtoPdb v.2023.1","authors":"S. Costagliola, J. Dias, M. Gershengorn, Adam J. Pawson, D. Segaloff, A. Themmen, G. Vassart","doi":"10.2218/gtopdb/f30/2023.1","DOIUrl":"https://doi.org/10.2218/gtopdb/f30/2023.1","url":null,"abstract":"Glycoprotein hormone receptors (provisional nomenclature [47]) are activated by a non-covalent heterodimeric glycoprotein made up of a common α chain (glycoprotein hormone common alpha subunit CGA, P01215), with a unique β chain that confers the biological specificity to FSH, LH, hCG or TSH. There is binding cross-reactivity across the endogenous agonists for each of the glycoprotein hormone receptors. The deglycosylated hormones appear to exhibit reduced efficacy at these receptors [122, 31].","PeriodicalId":14617,"journal":{"name":"IUPHAR/BPS Guide to Pharmacology CITE","volume":"16 6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88803894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-26DOI: 10.2218/gtopdb/f155/2023.1
I. Kerr
This family of 'half-transporters' act as homo- or heterodimers; particularly ABCG5 and ABCG8 are thought to be obligate heterodimers. The ABCG5/ABCG heterodimer sterol transporter structure has been determined [6], suggesting an extensive intracellular nucleotide binding domain linked to the transmembrane domains by a fold in the primary sequence. The functional ABCG2 transporter appears to be a homodimer with structural similarities to the ABCG5/ABCG8 heterodimer [10, 1].
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Pub Date : 2023-04-26DOI: 10.2218/gtopdb/f80/2023.1
W. Catterall, Edward Perez-Reyes, Terrance P. Snutch, Joerg Striessnig
Ca2+ channels are voltage-gated ion channels present in the membrane of most excitable cells. The nomenclature for Ca2+channels was proposed by [131] and approved by the NC-IUPHAR Subcommittee on Ca2+ channels [72]. Most Ca2+ channels form hetero-oligomeric complexes. The α1 subunit is pore-forming and provides the binding site(s) for practically all agonists and antagonists. The 10 cloned α1-subunits can be grouped into three families: (1) the high-voltage activated dihydropyridine-sensitive (L-type, CaV1.x) channels; (2) the high- to moderate-voltage activated dihydropyridine-insensitive (CaV2.x) channels and (3) the low-voltage-activated (T-type, CaV3.x) channels. Each α1 subunit has four homologous repeats (I-IV), each repeat having six transmembrane domains (S1-S6) and a pore-forming region between S5 and S6. Voltage-dependent gating is driven by the membrane spanning S4 segment, which contains highly conserved positive charges that respond to changes in membrane potential. All of the α1-subunit genes give rise to alternatively spliced products. At least for high-voltage activated channels, it is likely that native channels comprise co-assemblies of α1, β and α2-δ subunits. The γ subunits have not been proven to associate with channels other than the α1s skeletal muscle Cav1.1 channel. The α2-δ1 and α2-δ2 subunits bind gabapentin and pregabalin.
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