The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 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 (http://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 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/10.1111/bph.14748. 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‐2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

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.

Abstract-Angiotensin II (Ang II) has important actions on the heart via type 1 (AT 1 ) and type 2 (AT 2 ) receptors. The link between AT 1 receptor activation and the hypertrophy of cardiomyocytes is accepted, whereas the contribution of the AT 2 receptor, which reportedly antagonizes the AT 1 receptor, is contentious. This ambiguity is primarily based on in vivo approaches, in which the direct effect of the AT 2 receptor and its modulation of the AT 1 receptor (at the level of the cardiomyocyte) are difficult to establish. In this study, we used adenoviruses encoding AT 1 and AT 2 to coexpress these receptors in isolated cardiomyocytes, allowing a direct examination of the consequence of varying AT 1 /AT 2 stoichiometry on cardiomyocyte hypertrophy. Key Words: angiotensin II Ⅲ hypertrophy Ⅲ myocytes Ⅲ rats Ⅲ receptors L eft ventricular hypertrophy (LVH) is a major independent risk factor for premature death. 1 Extensive experimental and clinical evidence supports a role for the vasoactive hormone angiotensin II (Ang II) in the development of hypertension and the associated cardiomyocyte enlargement, which is a hallmark of LVH. Ang II binds with high affinity to type 1 (AT 1 ) and type 2 (AT 2 ) Ang II receptors, which are 7-transmembrane spanning, G-protein-coupled receptors. 2 AT 1 receptors are well characterized and mediate the established actions of Ang II, including vasoconstriction, aldosterone and vasopressin release, renal sodium reabsorption, increased collagen deposition, cellular proliferation, and, importantly, cardiomyocyte hypertrophy. The role of the AT 2 receptor is less clear, but current theories favor a role in opposing the actions of the AT 1 receptor. 3-7 AT 2 receptors are highly expressed in the fetus; however, after birth, the AT 2 receptor expression decreases to low levels. 2 In normal, adult human and rat hearts, AT 1 and AT 2 receptors are expressed, 8 -10 and they have been shown to be upregulated during cardiovascular pathologies. 8,9 The specific signaling pathways activated via the AT 2 receptor remain poorly resolved, although AT 2 receptors reportedly inhibit AT 1 receptor signaling pathways, such as extracellular signalregulated kinase 1/2 (ERK1/2) mitogen-activated protein kinases (MAPKs), by activating specific tyrosine or serine/ threonine phosphatases. 6,11,12 More recent evidence suggests functional heterodimerization between the AT 1 and AT 2

Phosphorylation of serine and threonine residues in the carboxyl-terminal region of many G-protein-coupled receptors directs the rapid uncoupling from signal transduction pathways. In Chinese hamster ovary cells, we have stably expressed a truncated mutant of the angiotensin II (AT1A) receptor devoid of the carboxyl-terminal 45 amino acids, encompassing 13 serine/threonine residues. One clone, designated TL314 to indicate truncation after leucine 314, expressed a single class of angiotensin II receptors with a dissociation constant of 1.08 nM and a receptor density of 560 fmol/mg of protein (approximately 75,000 receptors/cell). A nonhydrolyzable analog of GTP accelerated the angiotensin II-induced dissociation of [125I]angiotensin II from TL314 plasma membranes 3.6-fold, indicating G-protein coupling. In TL314 cells, angiotensin II stimulated the release of intracellular calcium and the induction of mitogen-activated protein kinase activity, the level of which were comparable with the full-length AT1A receptor. The AII-stimulated calcium response was rapidly desensitized in both full-length and truncated AT1A receptors. Interestingly, angiotensin II-induced endocytosis of the truncated receptor was almost completely inhibited, suggesting that a recognition motif within the carboxyl-terminal 45 amino acids of the AT1A receptor promotes sequestration. Thus, truncation of the AT1A receptor after leucine 314 inhibits agonist-induced internalization without affecting the capacity of the expressed protein to adopt the correct conformation necessary for high affinity binding of angiotensin II, coupling to G-proteins, and activation of signal transduction pathways. The rapid desensitization and refractoriness of the angiotensin II-induced calcium transient in the TL314 cell line, in which putative carboxyl-terminal phosphorylation sites are absent, suggests that the mechanism of AT1A receptor desensitization differs from that of other prototypical G-protein-coupled receptors.