Adenosine A2A receptor

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Adenosine A2A receptor
Identifiers
Symbol(s) ADORA2A; ADORA2; RDC8; hA2AR
External IDs OMIM: 102776 MGI99402 Homologene20166
RNA expression pattern

PBB GE ADORA2A 205013 s at tn.png

More reference expression data

Orthologs
Human Mouse
Entrez 135 11540
Ensembl ENSG00000128271 ENSMUSG00000020178
Uniprot P29274 Q2NLC1
Refseq NM_000675 (mRNA)
NP_000666 (protein)
NM_009630 (mRNA)
NP_033760 (protein)
Location Chr 22: 23.15 - 23.17 Mb Chr 10: 74.77 - 74.78 Mb
Pubmed search [1] [2]


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

Biochemistry

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.[1]


Function

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.

Recent research on adenosine receptor function, and adenosine receptor antagonists such as theophylline has led to several randomized controlled trials using these receptor antagonists to treat bradyasystolic arrest.[2][3][4][5][6][7][8]

Agonists and antagonists

Specific antagonists include KW6002 and SCH-58261, while specific agonists include CGS21680 and ATL-146e.[9]

References

  1. "Entrez Gene: ADORA2A adenosine A2A receptor". 
  2. Burton JH, Mass M, Menegazzi JJ, Yealy DM (1997). "Aminophylline as an adjunct to standard advanced cardiac life support in prolonged cardiac arrest". Annals of emergency medicine. 30 (2): 154–8. PMID 9250637. doi:10.1016/S0196-0644(97)70134-3. 
  3. Khoury MY, Moukarbel GV, Obeid MY, Alam SE (2001). "Effect of aminophylline on complete atrioventricular block with ventricular asystole following blunt chest trauma". Injury. 32 (4): 335–8. PMID 11325371. doi:10.1016/S0020-1383(00)00222-9. 
  4. Mader TJ, Bertolet B, Ornato JP, Gutterman JM (2000). "Aminophylline in the treatment of atropine-resistant bradyasystole". Resuscitation. 47 (2): 105–12. PMID 11008148. doi:10.1016/S0300-9572(00)00234-3. 
  5. Mader TJ, Smithline HA, Durkin L, Scriver G (2003). "A randomized controlled trial of intravenous aminophylline for atropine-resistant out-of-hospital asystolic cardiac arrest". Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 10 (3): 192–7. PMID 12615581. doi:10.1197/aemj.10.3.192. 
  6. Mader TJ, Gibson P (1997). "Adenosine receptor antagonism in refractory asystolic cardiac arrest: results of a human pilot study". Resuscitation. 35 (1): 3–7. PMID 9259053. doi:10.1016/S0300-9572(97)01097-6. 
  7. Perouansky M, Shamir M, Hershkowitz E, Donchin Y (1998). "Successful resuscitation using aminophylline in refractory cardiac arrest with asystole". Resuscitation. 38 (1): 39–41. PMID 9783508. doi:10.1016/S0300-9572(98)00079-3. 
  8. Viskin S, Belhassen B, Roth A, Reicher M, Averbuch M, Sheps D, Shalabye E, Laniado S (1993). "Aminophylline for bradyasystolic cardiac arrest refractory to atropine and epinephrine". Ann. Intern. Med. 118 (4): 279–81. PMID 8420445. 
  9. Jacobson KA, Gao ZG (2006). "Adenosine receptors as therapeutic targets". Nature reviews. Drug discovery. 5 (3): 247–64. PMID 16518376. doi:10.1038/nrd1983. 

Further reading

  • Ongini E, Adami M, Ferri C, Bertorelli R (1997). "Adenosine A2A receptors and neuroprotection.". Ann. N. Y. Acad. Sci. 825: 30–48. 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. 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. 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. 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. 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. 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. 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. 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. PMID 8020991. doi:10.1006/geno.1994.1181. 
  • 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. 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. PMID 8135838. doi:10.1006/bbrc.1994.1314. 
  • 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. PMID 8670304. doi:10.1006/bbrc.1996.0916. 
  • Jiang Q, Van Rhee AM, Kim J; et al. (1996). "Hydrophilic side chains in the third and seventh transmembrane helical domains of human A2A adenosine receptors are required for ligand recognition.". Mol. Pharmacol. 50 (3): 512–21. PMID 8794889. 
  • Ledent C, Vaugeois JM, Schiffmann SN; et al. (1997). "Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2A receptor.". Nature. 388 (6643): 674–8. PMID 9262401. doi:10.1038/41771. 
  • Koshiba M, Rosin DL, Hayashi N; et al. (1999). "Patterns of A2A extracellular adenosine receptor expression in different functional subsets of human peripheral T cells. Flow cytometry studies with anti-A2A receptor monoclonal antibodies.". Mol. Pharmacol. 55 (3): 614–24. PMID 10051547. 
  • Borgland SL, Castañón M, Spevak W, Parkinson FE (1999). "Effects of propentofylline on adenosine receptor activity in Chinese hamster ovary cell lines transfected with human A1, A2A, or A2B receptors and a luciferase reporter gene.". Can. J. Physiol. Pharmacol. 76 (12): 1132–8. PMID 10326835. 
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