The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is 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 almost 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.16177. 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-2023, and supersedes data presented in the 2021/22, 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

EXTRA-SYNAPTIC LOCATION OF ALPHA-2 AND NON-INNERVATED BETA-2 ADRENOCEPTORS IN THE VASCULAR SYSTEM OF THE PITHED NORMOTENSIVE RAT

The receptors involved in the pressor and tachycardic effects of catecholamines applied systemically or released from sympathetic nerve endings were compared. Intravenously administered (-)-epinephrine activated alpha-1, alpha-2, beta-1 and beta-2 adrenoceptors as demonstrated in pithed rats, using the alpha-1 sympatholytic drug prazosin, the alpha-2 adrenoceptor blocking substance rauwolscine, the beta-1 and beta-2 sympatholytic agent(-)-propranolol, the predominantly beta-1 adrenoceptor antagonist atenolol and the selective beta-2 adrenoceptor blocking agent ICI 118,551 as tools. (-)-Norepinephrine given i.v. proved to be an alpha-1, alpha-2 and beta-1 adrenoceptor agonist. 1,1-Dimethyl-4-phenylpiperazine iodide (DMPP) releases catecholamines from noradrenergic neurons and the adrenal medulla. The i.v. injection of DMPP into pithed rats caused an increase in diastolic pressure and heart rate by this indirect effect, which has been confirmed by pretreatment with reserpine and removal of the adrenals. After bilateral adrenalectomy, there occurred a release of mainly norepinephrine, only from the neurons. Catecholamines liberated by DMPP activated alpha-1 and beta-1 receptors and, at high doses of DMPP, alpha-2 and beta-2 adrenoceptors as well. Removal of both adrenal glands abolished the alpha-2 and beta-2 adrenoceptor-mediated effects. (-)-Norepinephrine released from neurons stimulated alpha-1 and beta-1 adrenoceptors only, although after i.v. administration of this catecholamine alpha-2 adrenoceptors were also activated. There was no indication for a beta-2 adrenoceptor-mediated vasodilation by neuronally released catecholamines. A beta-2 adrenoceptor-mediated effect, however, could be demonstrated by i.v. injection of (-)-epinephrine. The results can be explained by the presence of predominantly alpha-1 and beta-1 adrenoceptors in the postganglionic sympathetic synapses and an extrasynaptic location of alpha-2 and beta-2 adrenoceptors. The extrasynaptic receptors are possibly controlled by epinephrine from the adrenals