The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein‐coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

This paper, written by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) subcommittees for the angiotensin receptors, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions, and their likely physiological roles in health and disease. More information on these receptor families can be found in the Concise Guide to PHARMACOLOGY Angiotensins are a group of hormonal peptides and include angiotensin II and angiotensin 1-7 produced by the renin angiotensin system. The biology, pharmacology and biochemistry of the receptors for angiotensins were extensively reviewed recently. In the review, the receptor nomenclature committee was not emphatic on designating MAS1 as the angiotensin 1-7 receptor on the basis of lack of classical G protein signalling and desensitization in response to angiotensin 1-7, as well as a lack of consensus on confirmatory ligand pharmacological analyses. A review of recent publications (2013-2016) on the rapidly progressing research on angiotensin 1-7 revealed that MAS1 and two additional receptors can function as 'angiotensin 1-7 receptors', and this deserves further consideration. In this review we have summarized the information on angiotensin 1-7 receptors and their crosstalk with classical angiotensin II receptors in the context of the functions of the renin angiotensin system. It was concluded that the receptors for angiotensin II and angiotensin 1-7 make up a sophisticated cross-regulated signalling network that modulates the endogenous protective and pathogenic facets of the renin angiotensin system.

Angiotensinogen -a serpin family protein predominantly produced by the liver is systematically processed by proteases of the Renin Angiotensin system (RAS) generating hormone peptides. Specific cell surface receptors for at least three distinct angiotensin peptides produce distinct cellular signals that regulate system-wide physiological response to RAS. Two well characterized receptors are angiotensin type 1 receptor (AT1 receptor) and type 2 receptor (AT2 receptor).They respond to the octapeptide hormone angiotensin II. The oncogene product MAS is a putative receptor for Ang (1-7). While these are G-protein coupled receptors (GPCRs), the in vivo angiotensin IV binding sites may be type 2 trans-membrane proteins. These four receptors together regulate cardiovascular, hemodynamic, neurological, renal, and endothelial functions; as well as cell proliferation, survival, matrix-cell interactions and inflammation. Angiotensin receptors are important therapeutic targets for several diseases. Thus, researchers and pharmaceutical companies are focusing on drugs targeting AT1 receptor than AT2 receptor, MAS and AngIV binding sites. AT1 receptor blockers are the cornerstone of current treatment for hypertension, heart failure, renal failure and many types of vascular diseases including atherosclerosis, aortic aneurism and Marfan syndrome.

While orthosteric ligands of the angiotensin II (AngII) type 1 receptor (AT1R) are available for clinical and research applications, allosteric ligands are not known for this important G protein-coupled receptor (GPCR). Allosteric ligands are useful tools to modulate receptor pharmacology and subtype selectivity. Here, we report AT1R allosteric ligands for a potential application to block autoimmune antibodies. The epitope of autoantibodies for AT1R is outside the orthosteric pocket in the extracellular loop 2. A molecular dynamics simulation study of AT1R structure reveals the presence of a druggable allosteric pocket encompassing the autoantibody epitope. Small molecule binders were then identified for this pocket using structure-based high-throughput virtual screening. The top 18 hits obtained inhibited the binding of antibody to AT1R and modulated agonist-induced calcium response of AT1R. Two compounds out of 18 studied in detail exerted a negative allosteric modulator effect on the functions of the natural agonist AngII. They blocked antibody-enhanced calcium response and reactive oxygen species production in vascular smooth muscle cells as well as AngII-induced constriction of blood vessels, demonstrating their efficacy in vivo. Our study thus demonstrates the feasibility of discovering inhibitors of the disease-causing autoantibodies for GPCRs. Specifically, for AT1R, we anticipate development of more potent allosteric drug candidates for intervention in autoimmune maladies such as preeclampsia, bilateral adrenal hyperplasia, and the rejection of organ transplants.

Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [194], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [150]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.Table 1: Class A orphan GPCRs with putative endogenous ligands GPR3 GPR4 GPR6 GPR12 GPR15 GPR17 GPR20 GPR22 GPR26 GPR31 GPR34 GPR35 GPR37 GPR39 GPR50 GPR63 GRP65 GPR68 GPR75 GPR84 GPR87 GPR88 GPR132 GPR149 GPR161 GPR183 LGR4 LGR5 LGR6 MAS1 MRGPRD MRGPRX1 MRGPRX2 P2RY10 TAAR2 In addition the orphan receptors GPR18, GPR55 and GPR119 which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together (GPR18, GPR55 and GPR119).

No abstract

The actions of angiotensin II (Ang II) are mediated by AT 1 and AT 2 receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Angiotensin receptors [61, 152]), which have around 30% sequence similarity. The decapeptide angiotensin I, the octapeptide angiotensin II and the heptapeptide angiotensin III are endogenous ligands. losartan, candesartan, telmisartan, etc. are clinically used AT 1 receptor blockers. ContentsThis is a citation summary for Angiotensin receptors in the Guide to Pharmacology database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analyzers. Readers will almost certainly want to visit the relevant sections of the database which are given here under database links.GtoPdb is an expert-driven guide to pharmacological targets and the substances that act on them. GtoPdb is a reference work which is most usefully represented as an on-line database. As in any publication this work should be appropriately cited, and the papers it cites should also be recognized. This document provides a citation for the relevant parts of the database, and also provides a reference list for the research cited by those 1 parts.Please note that the database version for the citations given in GtoPdb are to the most recent preceding version in which the family or its subfamilies and targets were substantially changed. The links below are to the current version. If you need to consult the cited version, rather than the most recent version, please contact the GtoPdb curators.Inflammation influences vascular remodeling through AT2 receptor expression and signaling. Physiol. Genomics 2: 13-20 [PMID:11015577] 9. Akishita M, Iwai M, Wu L, Zhang L, Ouchi Y, Dzau VJ and Horiuchi M. (2000) Inhibitory effect of angiotensin II type 2 receptor on coronary arterial remodeling after aortic banding in mice. Circulation 102: 1684-9 [PMID:11015348] 10. Albiston AL, McDowall SG, Matsacos D, Sim P, Clune E, Mustafa T, Lee J, Mendelsohn FA, Simpson RJ and Connolly LM et al.. (2001) Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulinregulated aminopeptidase. J. Biol. Chem. 276: 48623-6 [PMID:11707427] 11. Albiston AL, Mustafa T, McDowall SG, Mendelsohn FA, Lee J and Chai SY. (2003) AT4 receptor is insulinregulated membrane aminopeptidase: potential mechanisms of memory enhancement. Trends Endocrinol. Metab. 14: 72-7 [PMID:12591177] 12. Alfakih K, Maqbool A, Sivananthan M, Walters K, Bainbridge G, Ridgway J, Balmforth AJ and Hall AS. (2004) Left ventricle mass index and the common, functional, X-linked angiotensin II type-2 receptor gene polymorphism (-1332 G/A) in patients with systemic hypertension. Hypertension 43: 1189-94 [PMID:15123577] 13. Allen AM, Moeller I, Jenkins TA, Zhuo J, Aldred GP, Chai SY and Mendelsohn FA. (1998) Angiotensin receptors in the nervous system. Brain Res. Bull. 47: 17-28 [PMID:9766385] 14. Asico LD, Ladines C, Fuchs S, Accili D, Carey RM, Semeraro C, Pocchiari F, Felder RA, Eisner GM and Jose PA. ...

CBZ alters the functional activity of ABCC2 through PXR, which in turn can interfere with therapy. Mutational analysis of residues revealed the importance of Gln285 in ligand interaction.