Adenosine A2A receptor: Wikis


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Adenosine A2A receptor

Crystallographic structure of the Adenosine A2A receptor (rainbow color cartoon diagram, N-terminus = blue, C-terminus = red) complexed with ZM-241,385 (stick diagram) based on the PDB 3EML coordinates.
Available structures
Symbols ADORA2A; ADORA2; RDC8; hA2AR
External IDs OMIM102776 MGI99402 HomoloGene20166 IUPHAR: A2A GeneCards: ADORA2A Gene
RNA expression pattern
PBB GE ADORA2A 205013 s at tn.png
More reference expression data
Species Human Mouse
Entrez 135 11540
Ensembl ENSG00000128271 ENSMUSG00000020178
UniProt P29274 Q2NLC1
RefSeq (mRNA) NM_000675 NM_009630
RefSeq (protein) NP_000666 NP_033760
Location (UCSC) Chr 22:
23.15 - 23.17 Mb
Chr 10:
74.77 - 74.78 Mb
PubMed search [1] [2]

The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, but also denotes the human gene encoding it.[1][2]



This protein is a member of the G protein-coupled receptor (GPCR) family which possess seven transmembrane alpha helices. The crystallographic structure of the adenosine A2A receptor PDB 3EML (see figure to the right) reveals a ligand binding pocket distinct from that of other structurally determined GPCRs (i.e., the beta-2 adrenergic receptor and rhodopsin).[3]



The actions of the A2A receptor are complicated by the fact that a variety of functional heteromers composed of a mixture of A2A subunits with subunits from other unrelated G-protein coupled receptors have been found in the brain, adding a further degree of complexity to the role of adenosine in modulation of neuronal activity. Hetereomers consisting of adenosine A1/A2A,[4][5] dopamine D2/A2A[6] and D3/A2A,[7] glutamate mGluR5/A 2A[8] and cannabinoid CB1/A2A[9] have all been observed, as well as CB1/A2A/D2 heterotrimers,[10] and the functional significance and endogenous role of these hybrid receptors is still only starting to be unravelled.[11][12][13]


The gene encodes a protein which is one of several receptor subtypes for adenosine. The activity of the encoded protein, a G protein-coupled receptor family member, is mediated by G proteins which activate adenylyl cyclase. The encoded protein is abundant in basal ganglia, vasculature and platelets and it is a major target of caffeine.[14]

Physiological role

As with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow.

The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. Just as in A1 receptors, this normally serves as a protective mechanism, but may be destructive in altered cardiac function.

The A2A receptor is also expressed in the brain, where it has important roles in the regulation of glutamate and dopamine release, making it a potential therapeutic target for the treatment of conditions such as insomnia, pain, depression, drug addiction and Parkinson's disease.[15][16][17][18][19][20][21]


A number of selective A2A ligands have been developed,[22][23][24][25][26][27][28][29][30][31][32][33] with several possible therapeutic applications.[34][35][36][37][38][39] Older research on adenosine receptor function, and non-selective adenosine receptor antagonists such as aminophylline, focused mainly on the role of adenosine receptors in the heart, and led to several randomized controlled trials using these receptor antagonists to treat bradyasystolic arrest.[40][41][42][43][44][45][46]

However the development of more highly selective A2A ligands has led towards other applications, with the most significant focus of research currently being the potential therapeutic role for A2A antagonists in the treatment of Parkinson's disease.[47][48][49][50]




Adenosine A2A receptor has been shown to interact with Dopamine receptor D2.[57]


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Further reading

  • Ongini E, Adami M, Ferri C, Bertorelli R (1997). "Adenosine A2A receptors and neuroprotection.". Ann. N. Y. Acad. Sci. 825: 30–48. doi:10.1111/j.1749-6632.1997.tb48412.x. PMID 9369973.  
  • Furlong TJ, Pierce KD, Selbie LA, Shine J (1992). "Molecular characterization of a human brain adenosine A2 receptor.". Brain Res. Mol. Brain Res. 15 (1-2): 62–6. doi:10.1016/0169-328X(92)90152-2. PMID 1331670.  
  • Makujina SR, Sabouni MH, Bhatia S, et al. (1992). "Vasodilatory effects of adenosine A2 receptor agonists CGS 21680 and CGS 22492 in human vasculature.". Eur. J. Pharmacol. 221 (2-3): 243–7. doi:10.1016/0014-2999(92)90708-C. PMID 1426003.  
  • Karlsten R, Gordh T, Post C (1992). "Local antinociceptive and hyperalgesic effects in the formalin test after peripheral administration of adenosine analogues in mice.". Pharmacol. Toxicol. 70 (6 Pt 1): 434–8. doi:10.1111/j.1600-0773.1992.tb00503.x. PMID 1438021.  
  • Libert F, Passage E, Parmentier M, et al. (1992). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.". Genomics 11 (1): 225–7. doi:10.1016/0888-7543(91)90125-X. PMID 1662665.  
  • Martinez-Mir MI, Probst A, Palacios JM (1992). "Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease.". Neuroscience 42 (3): 697–706. doi:10.1016/0306-4522(91)90038-P. PMID 1835521.  
  • Libert F, Parmentier M, Lefort A, et al. (1989). "Selective amplification and cloning of four new members of the G protein-coupled receptor family.". Science 244 (4904): 569–72. doi:10.1126/science.2541503. PMID 2541503.  
  • Kim J, Wess J, van Rhee AM, et al. (1995). "Site-directed mutagenesis identifies residues involved in ligand recognition in the human A2A adenosine receptor.". J. Biol. Chem. 270 (23): 13987–97. doi:10.1074/jbc.270.23.13987. PMID 7775460.  
  • Szondy Z (1995). "Adenosine stimulates DNA fragmentation in human thymocytes by Ca(2+)-mediated mechanisms.". Biochem. J. 304 ( Pt 3): 877–85. PMID 7818494.  
  • MacCollin M, Peterfreund R, MacDonald M, et al. (1994). "Mapping of a human A2A adenosine receptor (ADORA2) to chromosome 22.". Genomics 20 (2): 332–3. doi:10.1006/geno.1994.1181. PMID 8020991.  
  • Nonaka H, Ichimura M, Takeda M, et al. (1994). "KF17837 ((E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine), a potent and selective adenosine A2 receptor antagonist.". Eur. J. Pharmacol. 267 (3): 335–41. doi:10.1016/0922-4106(94)90159-7. PMID 8088373.  
  • Iwamoto T, Umemura S, Toya Y, et al. (1994). "Identification of adenosine A2 receptor-cAMP system in human aortic endothelial cells.". Biochem. Biophys. Res. Commun. 199 (2): 905–10. doi:10.1006/bbrc.1994.1314. PMID 8135838.  
  • Salmon JE, Brogle N, Brownlie C, et al. (1993). "Human mononuclear phagocytes express adenosine A1 receptors. A novel mechanism for differential regulation of Fc gamma receptor function.". J. Immunol. 151 (5): 2775–85. PMID 8360491.  
  • Peterfreund RA, MacCollin M, Gusella J, Fink JS (1996). "Characterization and expression of the human A2A adenosine receptor gene.". J. Neurochem. 66 (1): 362–8. PMID 8522976.  
  • Le F, Townsend-Nicholson A, Baker E, et al. (1996). "Characterization and chromosomal localization of the human A2A adenosine receptor gene: ADORA2A.". Biochem. Biophys. Res. Commun. 223 (2): 461–7. doi:10.1006/bbrc.1996.0916. PMID 8670304.  
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