, Volume 3, Issue 9, pp 623–629 | Cite as

The human A1 adenosine receptor: ligand binding properties, sites of somatic expression and chromosomal localization

  • Scott A. Rivkees
  • Mark E. Lasbury
  • Gary S. Stiles
  • Octavian Henegariu
  • Christine Curtis
  • Gail Vance


The A1 adenosine receptor (A1AR) exerts important biological effects in the mammalian biology. To provide insights into the role A1AR action in human physiology, we characterized the pharmacologic properties of the human A1AR, examined somatic sites of A1AR gene expression, and identified the chromosomal location of the human A1AR gene. Using stably transfected CHO cells, the ligand binding properties of human and rat A1ARs were directly compared. Saturation studies showed that the human and rat A1ARs had similar high affinity for the A1 agonist [3H]CCPA (human, Kd=517±64 pM; Bmax 438±29 fmol/mg of protein; rat, Kd=429±69 pM; Bmax 358±76 fmol/mg of protein). Competition studies performed using seven adenosine agonists and four adenosine antagonists also did not detect differences in the ligand binding properties among the rat and human A1ARs. Northern analysis of 16 human tissues revealed the presence of a single hybridizing transcript of 2.5 kb. Human A1AR receptor mRNA expression was greatest in brain and testis; lower levels of A1AR mRNA were present in heart, pancreas, kidney and spleen. Southern blotting and PCR analysis of human-rodent somatic cell hybrids showed that the A1AR gene is on human chromosome 1. Using fluorescence in situ hybridization, the human A1AR gene was further localized to the 1q32.1 region. These observations show that the human A1AR is a high affinity receptor that has ligand binding properties similar to the rat A1AR, human A1AR mRNA is heavily expressed in brain and testis, and the gene encoding the human A1AR is present on the long arm of chromosome 1.


adenosine adenosine receptors chromosome human 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ausubul, F. (1993).Current Protocols in Molecular Biology, p. 18.Google Scholar
  2. Bhattacharya, S., Dewitt, D.L., Burnatowska-Hledin, M., Smith, W.L. & Spielman, W.S. (1993).Gene,128, 285–288.PubMedCrossRefGoogle Scholar
  3. Collis, M.G. & Hourani, S.M. (1993).Trends Pharmacol. Sci.,14, 360–366.PubMedCrossRefGoogle Scholar
  4. Deckert, J., Berger, W., Kleopa, K., Heckers, S., Ransmayr, G., Heinsen, H., Beckmann, H. & Riederer, P. (1993).Neurosci. Lett. 150, 191–194.PubMedCrossRefGoogle Scholar
  5. During, M.J. & Spencer, D.D. (1992).Ann. Neurol.,32, 618–624.PubMedCrossRefGoogle Scholar
  6. Fastbom, J., Pazos, A., Probst, A. & Palacios, J.M. (1986).Neurosci. Lett.,65, 127–132.PubMedCrossRefGoogle Scholar
  7. Jarvis, M.F. & Willimans, M. (1990).Adenosine and Adenosine Receptors, (ed) Williams, M. Clifton: Humana, pp. 423–474.Google Scholar
  8. Libert, F., Parmentier, M., Lefort, A., Dinsart, C., Van Sande Maenhaut, C., Dumont, J.E. & Vassart, G. (1989).Science,244, 569–572.PubMedCrossRefGoogle Scholar
  9. Libert, F., Passage, E., Parmentier, M., Simons, M.J. & VassartMattei, M.G. (1991a).Genom.,11, 225–227.CrossRefGoogle Scholar
  10. Libert, F., Schiffmann, S.N., Lefort, A. & Parmentier, M. (1991b).EMBO J.,10, 1677–1682.PubMedGoogle Scholar
  11. Libert, F., Van Sande, J., Lefort, A., Czernilofsky, A., Dumont, J.E., Vassart, G., Ensinger, H.A. & Mendla, K.D. (1992).Biochem. Biophys. Res. Comm.,187, 919–926.PubMedCrossRefGoogle Scholar
  12. Londos, C., Cooper, D.M. & Wolff, J. (1980).Proc. Natl. Acad. Sci.,77, 2551–2554.PubMedCrossRefGoogle Scholar
  13. MacCollin, M., Peterfreund, R., MacDonald, M., Fink, J.S. & Gusella, J. (1994).Genom.,20, 332–333.CrossRefGoogle Scholar
  14. Mahan, L.C., McVittie, L.D., Smyk-Randall, E.M., Nakata, H., Monsma, F.J., Jr., Gerfen, C.R. & Sibley, D.R. (1991).Mol. Pharm.,40, 1–7.Google Scholar
  15. Marquardt, D.L., Walker, L.L. & Heinemann, S. (1994).J. Immunol.,152, 4508–4515.PubMedGoogle Scholar
  16. McPherson, G.A. (1985).J. Pharmacolog. Meth.,14, 213–228.CrossRefGoogle Scholar
  17. Nakate, H. (1992).Eur. J. Biochem.,206, 171–177.CrossRefGoogle Scholar
  18. Olah, M.E., Jacobson, K.A. & Stiles, G.L. (1994).J. Biol. Chem.,269, 24692–24698.PubMedGoogle Scholar
  19. Olah, M.E., Ren, H., Ostrowski, J., Jacobson, K.A. & Stiles, G.L. (1992).J. Biol. Chem.,267, 10764–10770.PubMedGoogle Scholar
  20. Ren, H. & Stiles, G.L. (1994a).J. Biol. Chem.,269, 3104–3110.PubMedGoogle Scholar
  21. Ren, H. & Stiles, G.L. (1994b).Proc. Natl. Acad. Sci.,91, 4864–4866.PubMedCrossRefGoogle Scholar
  22. Reppert, S.M., Weaver, D.R., Stehle, J.H. & Rivkees, S.A. (1991).Molec. Endocrinol.,5, 1037–1048.CrossRefGoogle Scholar
  23. Rivkees, S.A. (1994).Endocrinology,136, 2307–2313.CrossRefGoogle Scholar
  24. Rivkees, S.A. & Reppert, S.M. (1992).Molec. Endocrinol.,6, 1598–1604.CrossRefGoogle Scholar
  25. Rudolphi, K.A., Schubert, P., Parkinson, F.E. & Fredholm, B.B. (1992).Cerebrovasc. Brain Metab. Rev.,4, 346–369.PubMedGoogle Scholar
  26. Salvatore, C.A., Jacobson, M.A., Taylor, H.E., Linden, J. & Johnson, R.G. (1993).Proc. Natl. Acad. Sci.,90, 10365–10369.PubMedCrossRefGoogle Scholar
  27. Seabright, M. (1971).Lancet,2, 971–972.PubMedCrossRefGoogle Scholar
  28. Stiles, G.L. (1992).J. Biol. Chem.,267, 6451–6454.PubMedGoogle Scholar
  29. Townsend-Nicholson, A. & Schofield, P. R. (1994).J. Biol. Chem. 269, 2373–2376.PubMedGoogle Scholar
  30. Townsend-Nicholson, A. & Shine, J. (1992).Brain Res. Molec. Brain Res.,16, 365–370.CrossRefGoogle Scholar
  31. Trivedi, B.K., Bridges, A.J. & Bruns, R.E. (1990).Adenosine and Adenosine Receptors, (ed) Williams, M. Clifton: Humana Press, pp. 57–105.Google Scholar
  32. Tucker, A.L., Linden, J., Robeva, A.S., D'Angelo, D.D. & Lynch, K.R. (1992).Febs Lett.,297, 107–111.PubMedCrossRefGoogle Scholar
  33. Tucker, A.L. & Linden, J. (1993).Cardiovasc. Res.,27, 62–67.PubMedGoogle Scholar
  34. Tucker, A.L., Robeva, A.S., Taylor, H.E., Holeton, D., Bocker, M., Lynch, K.R. & Linden, J. (1994).J. Biol. Chem. 269, 27900–27906.PubMedGoogle Scholar
  35. Williams, M. & Jacobson, K.A. (1990).Adenosine and Adenosine Receptors, (ed) Williams, M. Clifton: Humana, pp. 17–56.Google Scholar
  36. Work, C., Hutchinson, K., Prasad, M., Bruns, R.F. & Fox, J.H. (1989).Arch. Biochem. Biophys. 268, 191–202.PubMedCrossRefGoogle Scholar
  37. Yunis, J.J. (1981).Hum. Path.,12, 540–549.PubMedCrossRefGoogle Scholar

Copyright information

© Stockton Press 1995

Authors and Affiliations

  • Scott A. Rivkees
    • 1
    • 2
    • 3
  • Mark E. Lasbury
    • 1
  • Gary S. Stiles
    • 5
  • Octavian Henegariu
    • 4
  • Christine Curtis
    • 4
  • Gail Vance
    • 4
  1. 1.Section of Pediatric EndocrinologyHerman B Wells Center for Pediatric ResearchIndianapolisUSA
  2. 2.Neurobiology ProgramIndiana University Medical SchoolIndianapolisUSA
  3. 3.Dept of Biochemistry and Molecular BiologyIndiana University Medical SchoolIndianapolisUSA
  4. 4.Dept of Molecular GeneticsIndiana University Medical SchoolIndianapolisUSA
  5. 5.Depts. of Medicine and PharmacologyDuke University Medical SchoolDurhamUSA

Personalised recommendations