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Adenosine receptors C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
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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 A2A adenosine receptors [12] have been described. The structures of an antagonist-bound A1 receptor [31] and an adenosine-bound A1 receptor-Gi 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 A2B receptor has also been elucidated [13]. Caffeine is a nonselective antagonist for adenosine receptors, while istradefylline, a selective A2A receptor antagonist, is on the market for the treatment of Parkinson's disease.
Receptors
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A1 receptor
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A2A receptor
C
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A2B receptor
C
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A3 receptor
C
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Further reading
* Key recommended reading is highlighted with an asterisk
* Borea PA, Varani K, Vincenzi F, Baraldi PG, Tabrizi MA, Merighi S, Gessi S. (2015) The A3 adenosine receptor: history and perspectives. Pharmacol Rev, 67 (1): 74-102. [PMID:25387804]
* Cronstein BN, Sitkovsky M. (2017) Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases. Nat Rev Rheumatol, 13 (1): 41-51. [PMID:27829671]
* Fredholm BB, IJzerman AP, Jacobson KA, Linden J, Müller CE. (2011) International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors--an update. Pharmacol Rev, 63 (1): 1-34. [PMID:21303899]
* Guo D, Heitman LH, IJzerman AP. (2017) Kinetic Aspects of the Interaction between Ligand and G Protein-Coupled Receptor: The Case of the Adenosine Receptors. Chem Rev, 117 (1): 38-66. [PMID:27088232]
* Göblyös A, Ijzerman AP. (2011) Allosteric modulation of adenosine receptors. Biochim Biophys Acta, 1808 (5): 1309-18. [PMID:20599682]
Headrick JP, Peart JN, Reichelt ME, Haseler LJ. (2011) Adenosine and its receptors in the heart: regulation, retaliation and adaptation. Biochim Biophys Acta, 1808 (5): 1413-28. [PMID:21094127]
* 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 A2A receptor antagonists: from caffeine to selective non-xanthines. Br J Pharmacol, 179 (14): 3496-3511. [PMID:32424811]
Lasley RD. (2011) Adenosine receptors and membrane microdomains. Biochim Biophys Acta, 1808 (5): 1284-9. [PMID:20888790]
* Mundell S, Kelly E. (2011) Adenosine receptor desensitization and trafficking. Biochim Biophys Acta, 1808 (5): 1319-28. [PMID:20550943]
* 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]
References
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NC-IUPHAR subcommittee and family contributors
Subcommittee members:
Adriaan P. IJzerman (Chairperson)
Bertil B. Fredholm (Past chairperson)
Kenneth A. Jacobson
Joel Linden
Christa E. Müller |
Other contributors:
Bruno G. Frenguelli (Past chairperson)
Rebecca Hills
Karl-Norbert Klotz
Ulrich Schwabe
Gary L. Stiles |
How to cite this family page
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.
Adenosine inhibits many intracellular ATP-utilising enzymes, including adenylyl cyclase (P-site). A pseudogene exists for the A2B adenosine receptor (ADORA2BP1) with 79% identity to the A2B adenosine receptor cDNA coding sequence, but which is unable to encode a functional receptor [41]. DPCPX also exhibits antagonism at A2B receptors (pKi 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 A2B receptors (KD ca. 30 and 60 nM respectively). [125I]AB-MECA also binds to A1 receptors [53]. [3H]CGS 21680 is relatively selective for A2A 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].