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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. (2020) Adenosine A2A receptor antagonists: from caffeine to selective non-xanthines. Br J Pharmacol, [Epub ahead of print]. [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
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Concise Guide to PHARMACOLOGY citation:
Alexander SP, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, Veale EL et al. (2021) THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors. Br J Pharmacol. 176 Suppl 1:S27-S156.
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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].