Adenosine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Adenosine Receptors [27]) are activated by the endogenous ligand adenosine (potentially inosine also at A₃ receptors). Crystal structures for the antagonist-bound [15,38,60,68], agonist-bound [55-56,81] and G protein-bound A_2A adenosine receptors [12] have been described. The structures of an antagonist-bound A₁ receptor [31] and an adenosine-bound A₁ receptor-G_i complex [20] have been resolved by cryo-electronmicroscopy. Another structure of an antagonist-bound A₁ receptor obtained with X-ray crystallography has also been reported [14]. The structure of the A_2B receptor has also been elucidated [13]. Caffeine is a nonselective antagonist for adenosine receptors, while istradefylline, a selective A_2A receptor antagonist, is on the market for the treatment of Parkinson's disease.

Adenosine inhibits many intracellular ATP-utilising enzymes, including adenylyl cyclase (P-site). A pseudogene exists for the A_2B adenosine receptor (ADORA2BP1) with 79% identity to the A_2B adenosine receptor cDNA coding sequence, but which is unable to encode a functional receptor [41]. DPCPX also exhibits antagonism at A_2B receptors (pK_i ca. 7,[2,53]). Antagonists at A₃ receptors exhibit marked species differences, such that only MRS1523 and MRS1191 are selective at the rat A₃ receptor. In the absence of other adenosine receptors, [³H]DPCPX and [³H]ZM 241385 can also be used to label A_2B receptors (K_D ca. 30 and 60 nM respectively). [¹²⁵I]AB-MECA also binds to A₁ receptors [53]. [³H]CGS 21680 is relatively selective for A_2A receptors, but may also bind to other sites in cerebral cortex [16,47]. [³H]NECA binds to other non-receptor elements, which also recognise adenosine [61]. XAC-BY630 has been described as a fluorescent antagonist for labelling A₁ adenosine receptors in living cells, although activity at other adenosine receptors was not examined [10].

* Key recommended reading is highlighted with an asterisk

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* IJzerman AP, Jacobson KA, Müller CE, Cronstein BN, Cunha RA. (2022) International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update. Pharmacol Rev, 74 (2): 340-372. [PMID:35302044]

* Jacobson KA, Gao ZG, Matricon P, Eddy MT, Carlsson J. (2022) Adenosine A_2A receptor antagonists: from caffeine to selective non-xanthines. Br J Pharmacol, 179 (14): 3496-3511. [PMID:32424811]

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* Vecchio EA, Baltos JA, Nguyen ATN, Christopoulos A, White PJ, May LT. (2018) New paradigms in adenosine receptor pharmacology: allostery, oligomerization and biased agonism. Br J Pharmacol, 175 (21): 4036-4046. [PMID:29679502]

* Wei CJ, Li W, Chen JF. (2011) Normal and abnormal functions of adenosine receptors in the central nervous system revealed by genetic knockout studies. Biochim Biophys Acta, 1808 (5): 1358-79. [PMID:21185258]

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Subcommittee members: Adriaan P. IJzerman (Chairperson) Professor of Medicinal Chemistry Leiden-Amsterdam Centre for Drug Research Gorlaeus Laboratories, Leiden University PO Box 9502 Leiden, 2300 RA, The Netherlands Bertil B. Fredholm (Past chairperson) Department of Physiology and Pharmacology Section of Molecular Neuropharmacology Karolinska Institutet Stockholm, 171 77, Sweden Kenneth A. Jacobson Molecular Recognition Section National Institutes of Health Building 8A, Room BIA-17 Bethesda, MD, 20892, USA Joel Linden La Jolla Institute for Allergy & Immunology 9420 Athena Circle La Jolla, CA 92037 USA Christa E. Müller Pharmazeutisches Institut Pharmazeutische Chemie I An der Immenburg 4 D-53121 Bonn, Germany

Other contributors: Bruno G. Frenguelli (Past chairperson) Department of Biological Sciences University of Warwick Coventry CV4 7AL UK Rebecca Hills (Past curator) Karl-Norbert Klotz Institut für Pharmakologie und Toxikologie Universität Würzburg D-97078 Würzburg Germany Ulrich Schwabe Pharmakologisches Institut der Universität Heidelberg Im Neuenheimer Feld 366 Heidelberg D-69120 Germany Gary L. Stiles Department of Medicine Cardiovascular Division Duke University Medical Center PO Box 3681 Durham NC 27710 USA