Adenosine A3 receptor

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Available structures
PDB Ortholog search: PDBe RCSB
Aliases ADORA3, A3AR, AD026, bA552M11.5, adenosine A3 receptor
External IDs MGI: 104847 HomoloGene: 550 GeneCards: 140
Genetically Related Diseases
Targeted by Drug
adenosine, BAY 60-6583, regadenoson, CCPA, CGS 21680, cyclopentyladenosine, caffeine, CGS 15943, DPCPX, flavone, galangin, Istradefylline, nicardipine, preladenant, rolofylline, sakuranetin, SCH442416, SCH 58261, theophylline, ZM-241385[2]
RNA expression pattern
PBB GE ADORA3 206171 at tn.png
More reference expression data
Species Human Mouse
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 1: 111.5 – 111.5 Mb Chr 3: 105.87 – 105.91 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

The adenosine A3 receptor, also known as ADORA3, is an adenosine receptor, but also denotes the human gene encoding it.


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 neutrophil degranulation 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).


Multiple transcript variants encoding different isoforms have been found for this gene.[5]

Therapeutic implications[edit]

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]

Selective Ligands[edit]

A number of selective A3 ligands are available.[8][9][10][11][12][13][14][15][16][17][18][19]

Agonists/Positive Allosteric Modulators[edit]

  • 2-(1-Hexynyl)-N-methyladenosine
  • CF-101 (IB-MECA)
  • CF-102
  • 2-Cl-IB-MECA
  • CP-532,903
  • Inosine[20]
  • LUF-6000
  • MRS-3558

Antagonists/Negative Allosteric Modulators[edit]

  • KF-26777
  • MRS-545
  • MRS-1191
  • MRS-1220
  • MRS-1334
  • MRS-1523
  • MRS-3777
  • MRE-3005-F20
  • MRE-3008-F20
  • PSB-11
  • OT-7999
  • VUF-5574
  • SSR161421[21][22]

Inverse Agonists[edit]


  1. ^ "Diseases that are genetically associated with ADORA3 view/edit references on wikidata". 
  2. ^ "Drugs that physically interact with Adenosine receptor A3 view/edit references on wikidata". 
  3. ^ "Human PubMed Reference:". 
  4. ^ "Mouse PubMed Reference:". 
  5. ^ "Entrez Gene: ADORA3 adenosine A3 receptor". 
  6. ^ Silverman MH, Strand V, Markovits D, Nahir M, Reitblat T, Molad Y, Rosner I, Rozenbaum M, Mader R, Adawi M, Caspi D, Tishler M, Langevitz P, Rubinow A, Friedman J, Green L, Tanay A, Ochaion A, Cohen S, Kerns WD, Cohn I, Fishman-Furman S, Farbstein M, Yehuda SB, Fishman P (January 2008). "Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial". J. Rheumatol. 35 (1): 41–8. PMID 18050382. 
  7. ^ Wan TC, Ge ZD, Tampo A, Mio Y, Bienengraeber MW, Tracey WR, Gross GJ, Kwok WM, Auchampach JA (January 2008). "The A3 adenosine receptor agonist CP-532,903 protects against myocardial ischemia/reperfusion injury via the sarcolemmal ATP sensitive potassium channel". J. Pharmacol. Exp. Ther. 324 (1): 234–43. doi:10.1124/jpet.107.127480. PMC 2435594free to read. PMID 17906066. 
  8. ^ Jeong LS, Lee HW, Jacobson KA, Lee SK, Chun MW (2005). "Development of potent and selective human A3 adenosine receptor agonists". Nucleic Acids Symposium Series (2004). 49 (49): 31–2. doi:10.1093/nass/49.1.31. PMID 17150618. 
  9. ^ Gao ZG, Jacobson KA (September 2007). "Emerging adenosine receptor agonists". Expert Opinion on Emerging Drugs. 12 (3): 479–92. doi:10.1517/14728214.12.3.479. PMID 17874974. 
  10. ^ Kim SK, Gao ZG, Jeong LS, Jacobson KA (December 2006). "Docking studies of agonists and antagonists suggest an activation pathway of the A3 adenosine receptor". Journal of Molecular Graphics & Modelling. 25 (4): 562–77. doi:10.1016/j.jmgm.2006.05.004. PMID 16793299. 
  11. ^ Ge ZD, Peart JN, Kreckler LM, Wan TC, Jacobson MA, Gross GJ, Auchampach JA (December 2006). "Cl-IB-MECA Reduces Ischemia/Reperfusion Injury in Mice by Activating the A3 Adenosine Receptor". The Journal of Pharmacology and Experimental Therapeutics. 319 (3): 1200–10. doi:10.1124/jpet.106.111351. PMC 2430759free to read. PMID 16985166. 
  12. ^ 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. PMID 17382926. 
  13. ^ 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. PMID 18000937. 
  14. ^ 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. PMID 18255292. 
  15. ^ 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. PMID 17959910. 
  16. ^ Gao ZG, Jacobson KA (April 2008). "Translocation of Arrestin Induced by Human A3 Adenosine Receptor Ligands in an Engineered Cell Line: Comparison with G Protein-dependent Pathways". Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 57 (4): 303–11. doi:10.1016/j.phrs.2008.02.008. PMC 2409065free to read. PMID 18424164. 
  17. ^ Miwatashi S, Arikawa Y, Matsumoto T, Uga K, Kanzaki N, Imai YN, Ohkawa S (August 2008). "Synthesis and biological activities of 4-phenyl-5-pyridyl-1,3-thiazole derivatives as selective adenosine A3 antagonists". Chemical & Pharmaceutical Bulletin. 56 (8): 1126–37. doi:10.1248/cpb.56.1126. PMID 18670113. [dead link]
  18. ^ Gao ZG, Ye K, Göblyös A, Ijzerman AP, Jacobson KA (2008). "Flexible modulation of agonist efficacy at the human A3 adenosine receptor by the imidazoquinoline allosteric enhancer LUF6000". BMC Pharmacology. 8: 20. doi:10.1186/1471-2210-8-20. PMC 2625337free to read. PMID 19077268. 
  19. ^ Bar-Yehuda S, Stemmer SM, Madi L, Castel D, Ochaion A, Cohen S, Barer F, Zabutti A, Perez-Liz G, Del Valle L, Fishman P (August 2008). "The A3 adenosine receptor agonist CF102 induces apoptosis of hepatocellular carcinoma via de-regulation of the Wnt and NF-kappaB signal transduction pathways". International Journal of Oncology. 33 (2): 287–95. PMID 18636149. 
  20. ^ Xiaowei Jin, Rebecca K. Shepherd, Brian R. Duling, and Joel Linden. "Inosine Binds to A3 Adenosine Receptors and Stimulates Mast Cell Degranulation"
  21. ^ 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. PMID 23219796. 
  22. ^ 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. PMID 23219789. 

Further reading[edit]

External links[edit]

  • "Adenosine Receptors: A3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.