Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1

Nature volume 350, pages 614–619 (1991)Cite this article

Abstract

DOPAMINE receptors belong to a superfamily of receptors that exert their biological effects through guanine nucleotide-binding (G) proteins. Two main dopamine receptor subtypes have been identified, D1 and D2, which differ in their pharmacological and biochemical characteristics. D1 stimulates adenylyl cyclase activity, whereas D2 inhibits it1–3. Both receptors are primary targets for drugs used to treat many psychomotor diseases, including Parkinson's disease and schizophrenia4,5. Whereas the dopamine D, receptor has been cloned6–9, biochemical and behavioural data indicate that dopamine D1-like receptors exist which either are not linked to adenylyl cyclase or display different pharmacological activities10,11. We report here the cloning of a gene encoding a 477-amino-acid protein with strong homology to the cloned Dt receptor. The receptor, called D5, binds drugs with a pharmacological profile similar to that of the cloned Dl receptor, but displays a 10-fold higher affinity for the endogenous agonist, dopamine. As with D1, the dopamine D5 receptor stimulates adenylyl cyclase activity. Northern blot and in situ hybridization analyses reveal that the receptor is neuron-specific, localized primarily within limbic regions of the brain; no messenger RNA was detected in kidney, liver, heart or parathyroid gland. The existence of a dopamine D1-like receptor with these characteristics had not been predicted and may represent an alternative pathway for dopamine-mediated events and regulation of D2 receptor activity12–14.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Kebabian, J. W. & Calne, D. B. Nature 277, 93–96 (1979).

    Article  CAS  ADS  Google Scholar 

  2. Seeman, P. Pharmac. Rev. 32, 229–313 (1980).

    CAS  Google Scholar 

  3. Niznik, H. B. Molec. cell. Endocrin. 54, 1–22 (1987).

    Article  CAS  Google Scholar 

  4. Seeman, P. Synapse 1, 133–152 (1987).

    Article  CAS  Google Scholar 

  5. Seeman, P. & Niznik, H. B. FASEB J. 4(10), 2737–2744 (1990).

    Article  CAS  Google Scholar 

  6. Sunahara, R. K. et al. Nature 347, 80–83 (1990).

    Article  CAS  ADS  Google Scholar 

  7. Zhou, Q.-Y. et al. Nature 347, 76–79 (1990).

    Article  CAS  ADS  Google Scholar 

  8. Dearry, A. G. et al. Nature 347, 72–76 (1990).

    Article  CAS  ADS  Google Scholar 

  9. Monsma, F. J., Mahan, L. C., McVittie, L. D., Gerfen, C. R. & Sibley, D. R. Proc. natn. Acad. Sci. U.S.A. 87, 6723–6727 (1990).

    Article  CAS  ADS  Google Scholar 

  10. Andersen, P. H. et al. Trends Pharmacol. Sci. 11, 231–234 (1990).

    Article  CAS  Google Scholar 

  11. Felder, R. A., Felder, C. C., Eisner, G. M. & Jose, P. A. Am. J. Physiol. 257, F315–F327 (1989).

    Article  CAS  Google Scholar 

  12. Waddington, J. L. & O'Boyle, K. M. Pharmac. Ther. 43, 1–52 (1989).

    Article  CAS  Google Scholar 

  13. Clark, D. & White, F. J. Synapse 1, 347–388 (1987).

    Article  CAS  ADS  Google Scholar 

  14. Seeman, P., Niznik, H. B., Guan, H.-C., Booth, G. & Ulpian, C. Proc. natn. Acad. Sci. U.S.A. 86, 10156–10160 (1989).

    Article  CAS  ADS  Google Scholar 

  15. O'Dowd, B. F., Lefkowitz, R. J. & Caron, M. G. A. Rev. Neurosci. 12, 67–83 (1989).

    Article  CAS  Google Scholar 

  16. Kozak, M. Nucleic Acids Res. 12, 857–873 (1984).

    Article  CAS  Google Scholar 

  17. Bunzow, J. R. et al. Nature 336, 783–787 (1988).

    Article  CAS  ADS  Google Scholar 

  18. Sokoloff, P., Giros, B., Martres, M. P., Bouthenet, M. L. & Schwartz, J. C. Nature 347, 146–151 (1990).

    Article  CAS  ADS  Google Scholar 

  19. Van Tol, H. H. M. et al. Nature, 350, 610–614 (1991).

    Article  CAS  ADS  Google Scholar 

  20. Selbie, L. A., Hayes, G. & Shine, J. DNA 8, 683–989 (1989).

    Article  CAS  Google Scholar 

  21. Strader, C. D., Sigal, S. S. & Dixon, R. A. FASEB J. 3, 1825–1832 (1989).

    Article  CAS  Google Scholar 

  22. O'Dowd, B. F., Hnatowich, M., Caron, M. G., Lefkowitz, R. J. & Bouvier, M. J. biol. Chem. 264, 7564–7569 (1989).

    CAS  PubMed  Google Scholar 

  23. Bonner, T. I. et al. Neuron 1, 403–410 (1988).

    Article  CAS  Google Scholar 

  24. Seeman, P. et al. Neuropsychopharmacology 1, 5–15 (1987).

    Article  CAS  Google Scholar 

  25. Albert, P. R., Neve, K. A., Bunzow, J. R. & Civelli, O. J. biol. Chem. 265(4), 2098–2104 (1990).

    CAS  PubMed  Google Scholar 

  26. Ehrlich, M. E., Kurihara, T. & Greengard, P. J. molec. Neurosci. 2, 1–10 (1990).

    Article  CAS  Google Scholar 

  27. Kozak, M. J. Cell Biol. 103, 1–7 (1988).

    Article  Google Scholar 

  28. Bjorklund, A., Lindvall, O. in Handbook of Chemical Neuroanatomy (eds Bjorklund, A. & Hokfeld, T.) Vol. 2(A) 55–122 (Elsevier, Amsterdam, 1984).

    Google Scholar 

  29. Savasta, M., Dubois, A. & Scatton, B. Brain Res. 375, 291–301 (1986).

    Article  CAS  Google Scholar 

  30. Cortes, R., Gueye, B., Pazos, A., Probst, A. & Palacios, J. M. Neuroscience 28(2), 263–273 (1989).

    Article  CAS  Google Scholar 

  31. Diop, L., Gottberg, E., Briere, R., Grondin, L. & Reader, T. M. Synapse 2, 395–405 (1988).

    Article  CAS  Google Scholar 

  32. Besson, M.-J., Graybiel, A. M. & Nastuk, M. A. Neuroscience 1, 101–119 (1988).

    Article  Google Scholar 

  33. Ongini, E. & Longo, V. G. Int Rev. Neurobiol. 31, 239–255 (1989).

    Article  CAS  Google Scholar 

  34. Niznik, H. B. et al. Biochemistry 27, 7594–7599 (1988).

    Article  CAS  Google Scholar 

  35. Niznik, H. B., Jarvie, K. R. & Brown, E. M. Biochemistry 28, 6925–6930 (1989).

    Article  CAS  Google Scholar 

  36. O'Dowd, B. F. et al. FEBS Lett. 262(1), 8–12 (1990).

    Article  CAS  Google Scholar 

  37. Chen, C. & Okayama, H. Molec. cell. Biol. 7, 2745–2752 (1987).

    Article  CAS  Google Scholar 

  38. Salomon, Y. in Advances in Cyclic Nucleotide Research. (eds Brooker, G., Greengard, P. & Robison, G. A.) Vol. 10 (Raven, New York, 1979).

    Google Scholar 

  39. McMaster, G. K. & Carmichael, G. G. Proc. natn. Acad. Sci. U.S.A 74, 4835 (1977).

    Article  CAS  ADS  Google Scholar 

  40. Shivers, B. D., Schachter, B. S. & Pfaff, D. W. Meth. Enzym. 124, 497–510 (1986).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada

    Roger K. Sunahara, Hong-Chang Guan, Brian F. O'Dowd, Philip Seeman, Lisanne G. Laurier, Gordon Ng, Susan R. George, Joeseph Torchia & Hubert H. M. Van Tol

  2. Department of Psychiatry, University of Toronto, Toronto, Ontario, M5S 1A8, Canada

    Philip Seeman, Hubert H. M. Van Tol & Hyman B. Niznik

  3. Addiction Research Foundation, 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada

    Brian F. O'Dowd

  4. Laboratory of Molecular Neurobiology, Clarke Institute of Psychiatry, 250 College Street, Toronto, Ontario, M5T 1R8, Canada

    Hubert H. M. Van Tol & Hyman B. Niznik

Authors
  1. Roger K. Sunahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong-Chang Guan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian F. O'Dowd
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philip Seeman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lisanne G. Laurier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gordon Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Susan R. George
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Joeseph Torchia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hubert H. M. Van Tol
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hyman B. Niznik
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sunahara, R., Guan, HC., O'Dowd, B. et al. Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature 350, 614–619 (1991). https://doi.org/10.1038/350614a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/350614a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing