PR00553

ADENOSINA2AR

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short nameADENOSINA2AR

Description
Imported from IPR001513

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups
[7]
. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence
[3]
. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF)
[3, 10, 9, 8, 6]
. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice
[7]
. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs
[5]
.

The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices
[1, 2, 4]
.

In addition to their role in energy metabolism, purines (especially adenosine and adenine nucleotides) produce a wide range of pharmacological effects mediated by activation of cell surface receptors. Distinct receptors exist for adenosine. In the periphery, the main effects of adenosine include vasodilation, bronchoconstriction, immunosuppresion, inhibition of platelet aggregation, cardiac depression, stimulation of nociceptive afferents, inhibition of neurotransmitter release and inhibition of the release of other factors, e.g. hormones. In the CNS, adenosine exerts a pre- and post-synaptic depressant action, reducing motor activity, depressing respiration, inducing sleep and relieving anxiety. The physiological role of adenosine is thought to be to adjust energy demands in line with oxygen supply. Many of the clinical actions of methylxanthines are thought to be mediated through antagonism of adenosine receptors. Four subtypes of receptor have been identified, designated A1, A2A, A2B and A3.

A2A receptors have a limited distribution in the brain and are found in the striatum, olfactory tubercle and nucleus accumbens. In the periphery, A2 receptors mediate vasodilation, immunosuppression, inhibition of platelet aggregation and gluconeogenesis. The receptors activate adenylyl cyclase through G proteins.

References
Imported from IPR001513

1.G proteins in signal transduction. Birnbaumer L. Annu. Rev. Pharmacol. Toxicol. 30, 675-705, (1990). View articlePMID: 2111655

2.G protein involvement in receptor-effector coupling. Casey PJ, Gilman AG. J. Biol. Chem. 263, 2577-80, (1988). View articlePMID: 2830256

3.Fingerprinting G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 7, 195-203, (1994). View articlePMID: 8170923

4.Design of a discriminating fingerprint for G-protein-coupled receptors. Attwood TK, Findlay JB. Protein Eng. 6, 167-76, (1993). View articlePMID: 8386361

5.G protein-coupled receptor deorphanizations. Civelli O, Reinscheid RK, Zhang Y, Wang Z, Fredriksson R, Schioth HB. Annu. Rev. Pharmacol. Toxicol. 53, 127-46, (2013). PMID: 23020293

6.Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse. Bjarnadottir TK, Gloriam DE, Hellstrand SH, Kristiansson H, Fredriksson R, Schioth HB. Genomics 88, 263-73, (2006). View articlePMID: 16753280

7.The G protein-coupled receptor repertoires of human and mouse. Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, Brown A, Rodriguez SS, Weller JR, Wright AC, Bergmann JE, Gaitanaris GA. Proc. Natl. Acad. Sci. U.S.A. 100, 4903-8, (2003). View articlePMID: 12679517

8.IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Harmar AJ, Hills RA, Rosser EM, Jones M, Buneman OP, Dunbar DR, Greenhill SD, Hale VA, Sharman JL, Bonner TI, Catterall WA, Davenport AP, Delagrange P, Dollery CT, Foord SM, Gutman GA, Laudet V, Neubig RR, Ohlstein EH, Olsen RW, Peters J, Pin JP, Ruffolo RR, Searls DB, Wright MW, Spedding M. Nucleic Acids Res. 37, D680-5, (2009). View articlePMID: 18948278

9.International Union of Pharmacology. XLVI. G protein-coupled receptor list. Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, Spedding M, Harmar AJ. Pharmacol. Rev. 57, 279-88, (2005). View articlePMID: 15914470

10.GCRDb: a G-protein-coupled receptor database. Kolakowski LF Jr. Recept. Channels 2, 1-7, (1994). PMID: 8081729

Supplementary References

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