Adenosine A3 receptors are G protein-coupled receptors that couple to Gi/Gq and are involved in a variety of intracellular signaling pathways and physiological functions. It mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophildegranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and neurodegenerative effects, and it may also mediate both cell proliferation and cell death[citation needed].
Recent publications demonstrate that adenosine A3 receptor antagonists (SSR161421) could have therapeutic potential in bronchial asthma (17,18).
Gene[]
Multiple transcript variants encoding different isoforms have been found for this gene.[5]
Therapeutic implications[]
An adenosine A3 receptor agonist (CF-101) is in clinical trials for the treatment of rheumatoid arthritis.[6]
In a mouse model of infarction the A3 selective agonist CP-532,903 protected against myocardial ischemia and reperfusion injury.[7]
^Bevan N, Butchers PR, Cousins R, Coates J, Edgar EV, Morrison V, Sheehan MJ, Reeves J, Wilson DJ (June 2007). "Pharmacological characterisation and inhibitory effects of (2R,3R,4S,5R)-2-(6-amino-2-{[(1S)-2-hydroxy-1-(phenylmethyl)ethyl]amino}-9H-purin-9-yl)-5-(2-ethyl-2H-tetrazol-5-yl)tetrahydro-3,4-furandiol, a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". European Journal of Pharmacology. 564 (1–3): 219–25. doi:10.1016/j.ejphar.2007.01.094. PMID17382926.
^Priego EM, Pérez-Pérez MJ, von Frijtag Drabbe Kuenzel JK, de Vries H, Ijzerman AP, Camarasa MJ, Martín-Santamaría S (January 2008). "Selective human adenosine A3 antagonists based on pyrido[2,1-f]purine-2,4-diones: novel features of hA3 antagonist binding". ChemMedChem. 3 (1): 111–9. doi:10.1002/cmdc.200700173. hdl:10261/82277. PMID18000937. S2CID7128294.
^Jeong LS, Lee HW, Kim HO, Tosh DK, Pal S, Choi WJ, Gao ZG, Patel AR, Williams W, Jacobson KA, Kim HD (March 2008). "Structure-activity relationships of 2-chloro-N6-substituted-4'-thioadenosine-5'-N,N-dialkyluronamides as human A3 adenosine receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 18 (5): 1612–6. doi:10.1016/j.bmcl.2008.01.070. PMID18255292.
^Cordeaux Y, Briddon SJ, Alexander SP, Kellam B, Hill SJ (March 2008). "Agonist-occupied A3 adenosine receptors exist within heterogeneous complexes in membrane microdomains of individual living cells". The FASEB Journal. 22 (3): 850–60. doi:10.1096/fj.07-8180com. PMID17959910. S2CID10705640.
^Mikus EG, Szeredi J, Boer K, Tímári G, Finet M, Aranyi P, Galzin AM (December 2012). "Evaluation of SSR161421, a novel orally active adenosine A(3) receptor antagonist on pharmacology models". Eur. J. Pharmacol. 699 (1–3): 172–179. doi:10.1016/j.ejphar.2012.11.049. PMID23219796.
^Mikus EG, Boér K, Timári G, Urbán-Szabó K, Kapui Z, Szeredi J, Gerber K, Szabó T, Bátori S, Finet M, Arányi P, Galzin AM (December 2012). "Interaction of SSR161421, a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. Pharmacol. 699 (1–3): 62–66. doi:10.1016/j.ejphar.2012.11.046. PMID23219789.
Further reading[]
Klotz KN (2001). "Adenosine receptors and their ligands". Naunyn Schmiedebergs Arch. Pharmacol. 362 (4–5): 382–91. doi:10.1007/s002100000315. PMID11111832. S2CID12938732.
Monitto CL, Levitt RC, DiSilvestre D, Holroyd KJ (1995). "Localization of the A3 adenosine receptor gene (ADORA3) to human chromosome 1p". Genomics. 26 (3): 637–8. doi:10.1016/0888-7543(95)80194-Q. PMID7607699.
Bouma MG, Jeunhomme TM, Boyle DL, et al. (1997). "Adenosine inhibits neutrophil degranulation in activated human whole blood: involvement of adenosine A2 and A3 receptors". J. Immunol. 158 (11): 5400–8. PMID9164961.
Atkinson MR, Townsend-Nicholson A, Nicholl JK, et al. (1998). "Cloning, characterisation and chromosomal assignment of the human adenosine A3 receptor (ADORA3) gene". Neurosci. Res. 29 (1): 73–9. doi:10.1016/S0168-0102(97)00073-4. PMID9293494. S2CID36060683.
Palmer TM, Harris CA, Coote J, Stiles GL (1997). "Induction of multiple effects on adenylyl cyclase regulation by chronic activation of the human A3 adenosine receptor". Mol. Pharmacol. 52 (4): 632–40. doi:10.1124/mol.52.4.632. PMID9380026.
Murphy WJ, Eizirik E, Johnson WE, et al. (2001). "Molecular phylogenetics and the origins of placental mammals". Nature. 409 (6820): 614–8. Bibcode:2001Natur.409..614M. doi:10.1038/35054550. PMID11214319. S2CID4373847.
Broussas M, Cornillet-Lefèbvre P, Potron G, Nguyên P (2003). "Adenosine inhibits tissue factor expression by LPS-stimulated human monocytes: involvement of the A3 adenosine receptor". Thromb. Haemost. 88 (1): 123–30. doi:10.1055/s-0037-1613164. PMID12152652.