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Gene Review

Adora3  -  adenosine A3 receptor

Mus musculus

Synonyms: 1700001D09Rik, 4930578J19Rik, A3AR, A3R, AA3R, ...
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Disease relevance of Adora3

  • Curiously, this effect was mimicked by ischemia, which acutely reduced Adora3 levels and induced Adora2B in young (but not old) hearts [1].
  • Activation of the Gi protein-coupled A3 adenosine receptor (A3AR) has been implicated in the inhibition of melanoma cell growth by deregulating protein kinase A and key components of the Wnt signaling pathway [2].
  • The receptors were quantitated by the agonist 125I-labeled APNEA (aminophenylethyladenosine), an A3AR agonist, which yielded Bmax and Kd values of 826 fmol/mg protein and 34 nM, respectively [3].
  • We used mice with genetic disruption of the A3 adenosine receptor (AR) gene (A3AR(-/-)mice) to assess the in vivo role of the A3AR in modulating myocardial ischemia/reperfusion injury and preconditioning (PC) [4].
  • Further, A3AR-/- mice were more vulnerable to hippocampal pyramidal neuron damage following episodes of carbon monoxide (CO)-induced hypoxia [5].

High impact information on Adora3


Chemical compound and disease context of Adora3


Biological context of Adora3

  • The mouse A3 receptor gene (Adora3) mapped to chromosome 3, in tight linkage with DNA marker D3Bir15 [9].
  • Paradoxically, overexpression of both A1-AR and A3-AR is associated with changes in the cardiac phenotype [10].
  • A3AR(-/-) mice have basal heart rates and arterial blood pressures indistinguishable from A3AR(+/+) mice [7].
  • In accordance with Northern blot analysis of A3AR mRNA, transient transfection experiments showed that the promoter activity of this fragment was significant in VSMC and astrocytes and high in mast cells [11].
  • The mouse A3AR gene fragment available to us has 3 kb of coding sequences, composed of two exons separated by a single intron, and 2.3 kb of 5' noncoding region [11].

Anatomical context of Adora3

  • Here we show that stimulation of cultured murine astrocytes with the selective adenosine A3 receptor agonist 2-chloro-N6-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (CL-IB-MECA) induced the release of CCL2 [12].
  • In A3AR(-/-) mice, the density of A(1) and A(2A) adenosine receptor subtypes was the same as in A3AR(+/+) mice as determined by radioligand binding to brain membranes [7].
  • As in black Swiss outbred mice and other mammalian species, reducing aqueous humor inflow with acetazolamide lowered IOP and administering water intraperitoneally increased IOP in both A3AR-/- and A3AR+/+ mice [13].
  • Surprisingly, infarct size induced by 30 min of coronary artery occlusion and 24 h of reperfusion was 35% smaller in A3AR(-/-)compared to wild-type mice (A3AR(+/+)) [4].
  • This finding is intriguing in view of the reported effects of sustained activation of the A3AR on induction of DNA fragmentation and apoptosis in cultured myocytes and other cell types [14].

Associations of Adora3 with chemical compounds

  • Chromosomal mapping of the mouse A3 adenosine receptor gene, Adora3 [9].
  • Conversely, A3AR agonism (100 nM Cl-IB-MECA) did reduce effects of I/R (pEC50s=8.0+/-0.1 and 7.3+/-0.1 for 2-chloroadenosine and ADP, respectively), whereas antagonism (100 nM MRS1220) was without effect [15].
  • Functionally, activation of these A3AR stimulated the production of inositol 1,4,5-triphosphate, leading to an increase in the level of intracellular Ca2+ [3].
  • The A3-selective agonist IB-MECA did not affect IOP in A3-knockout mice, but raised it in A3AR+/+ mice [13].
  • A3-AR mRNA was not found in any nephron segment [16].

Regulatory relationships of Adora3


Other interactions of Adora3


Analytical, diagnostic and therapeutic context of Adora3

  • Real-time PCR analyses revealed an age-related decline in Adora3 levels and induction of Adora2B [1].
  • Northern blotting studies using poly(A+) RNA from RBL-2H3 cells detected two transcripts of 2.0 and 3.5 kilobases, which hybridized to an A3AR cDNA but not to the A1 or A2AR cDNA probes [3].
  • To this end, different ages of mouse embryos (8.5 days and older) were subjected to in situ hybridization with an A3AR riboprobe [14].
  • Specifically, in situ ischemic preconditioning conferred cardioprotection in A1 AR-/-, A2A AR-/-, or A3 AR-/- mice but not in A2B AR-/- mice or in wild-type mice after inhibition of the A2B AR [20].
  • High tissue adenosine levels have been shown to adversely affect microvascular function and tissue survival after an ischemic episode, and previous work in this laboratory has shown that adenosine causes arteriolar constriction and degranulation of mast cells via the A3 receptor (A3AR) [21].


  1. Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium. Ashton, K.J., Nilsson, U., Willems, L., Holmgren, K., Headrick, J.P. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  2. A3 adenosine receptor activation in melanoma cells: association between receptor fate and tumor growth inhibition. Madi, L., Bar-Yehuda, S., Barer, F., Ardon, E., Ochaion, A., Fishman, P. J. Biol. Chem. (2003) [Pubmed]
  3. The A3 adenosine receptor is the unique adenosine receptor which facilitates release of allergic mediators in mast cells. Ramkumar, V., Stiles, G.L., Beaven, M.A., Ali, H. J. Biol. Chem. (1993) [Pubmed]
  4. Targeted deletion of the A3 adenosine receptor confers resistance to myocardial ischemic injury and does not prevent early preconditioning. Guo, Y., Bolli, R., Bao, W., Wu, W.J., Black, R.G., Murphree, S.S., Salvatore, C.A., Jacobson, M.A., Auchampach, J.A. J. Mol. Cell. Cardiol. (2001) [Pubmed]
  5. Behavioral characterization of mice lacking the A3 adenosine receptor: sensitivity to hypoxic neurodegeneration. Fedorova, I.M., Jacobson, M.A., Basile, A., Jacobson, K.A. Cell. Mol. Neurobiol. (2003) [Pubmed]
  6. Activation of murine lung mast cells by the adenosine A3 receptor. Zhong, H., Shlykov, S.G., Molina, J.G., Sanborn, B.M., Jacobson, M.A., Tilley, S.L., Blackburn, M.R. J. Immunol. (2003) [Pubmed]
  7. Disruption of the A(3) adenosine receptor gene in mice and its effect on stimulated inflammatory cells. Salvatore, C.A., Tilley, S.L., Latour, A.M., Fletcher, D.S., Koller, B.H., Jacobson, M.A. J. Biol. Chem. (2000) [Pubmed]
  8. Antitumor effect of cordycepin (3'-deoxyadenosine) on mouse melanoma and lung carcinoma cells involves adenosine A3 receptor stimulation. Nakamura, K., Yoshikawa, N., Yamaguchi, Y., Kagota, S., Shinozuka, K., Kunitomo, M. Anticancer Res. (2006) [Pubmed]
  9. Chromosomal mapping of the mouse A3 adenosine receptor gene, Adora3. Zhao, Z., Ravid, S., Ravid, K. Genomics (1995) [Pubmed]
  10. Regulated overexpression of the A1-adenosine receptor in mice results in adverse but reversible changes in cardiac morphology and function. Funakoshi, H., Chan, T.O., Good, J.C., Libonati, J.R., Piuhola, J., Chen, X., MacDonnell, S.M., Lee, L.L., Herrmann, D.E., Zhang, J., Martini, J., Palmer, T.M., Sanbe, A., Robbins, J., Houser, S.R., Koch, W.J., Feldman, A.M. Circulation (2006) [Pubmed]
  11. Characterization of the mouse A3 adenosine receptor gene: exon/intron organization and promoter activity. Zhao, Z., Francis, C., Ravid, K. Genomics (1999) [Pubmed]
  12. Adenosine A3 receptor-induced CCL2 synthesis in cultured mouse astrocytes. Wittendorp, M.C., Boddeke, H.W., Biber, K. Glia (2004) [Pubmed]
  13. Knockout of A3 adenosine receptors reduces mouse intraocular pressure. Avila, M.Y., Stone, R.A., Civan, M.M. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  14. Overexpression of A3 adenosine receptors in smooth, cardiac, and skeletal muscle is lethal to embryos. Zhao, Z., Yaar, R., Ladd, D., Cataldo, L.M., Ravid, K. Microvasc. Res. (2002) [Pubmed]
  15. Adenosine receptor-mediated coronary vascular protection in post-ischemic mouse heart. Zatta, A.J., Matherne, G.P., Headrick, J.P. Life Sci. (2006) [Pubmed]
  16. Gene expression of adenosine receptors along the nephron. Vitzthum, H., Weiss, B., Bachleitner, W., Krämer, B.K., Kurtz, A. Kidney Int. (2004) [Pubmed]
  17. Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-alpha production through inhibition of PI 3-kinase/Akt and NF-kappaB activation in murine BV2 microglial cells. Lee, J.Y., Jhun, B.S., Oh, Y.T., Lee, J.H., Choe, W., Baik, H.H., Ha, J., Yoon, K.S., Kim, S.S., Kang, I. Neurosci. Lett. (2006) [Pubmed]
  18. Suppression of inflammation by low-dose methotrexate is mediated by adenosine A2A receptor but not A3 receptor activation in thioglycollate-induced peritonitis. Montesinos, M.C., Desai, A., Cronstein, B.N. Arthritis Res. Ther. (2006) [Pubmed]
  19. Regulation of the A3 adenosine receptor gene in vascular smooth muscle cells: role of a cAMP and GATA element. Yaar, R., Cataldo, L.M., Tzatsos, A., Francis, C.E., Zhao, Z., Ravid, K. Mol. Pharmacol. (2002) [Pubmed]
  20. Cardioprotection by ecto-5'-nucleotidase (CD73) and A2B adenosine receptors. Eckle, T., Krahn, T., Grenz, A., Köhler, D., Mittelbronn, M., Ledent, C., Jacobson, M.A., Osswald, H., Thompson, L.F., Unertl, K., Eltzschig, H.K. Circulation (2007) [Pubmed]
  21. Adenosine A3 receptor activation modulates the capillary endothelial glycocalyx. Platts, S.H., Duling, B.R. Circ. Res. (2004) [Pubmed]
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