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

Naturevolume 350, pages614–619 (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 andin 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.

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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

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  2. Hong-Chang Guan

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  3. Brian F. O'Dowd

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  4. Philip Seeman

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  5. Lisanne G. Laurier

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  6. Gordon Ng

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  7. Susan R. George

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  8. Joeseph Torchia

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  9. Hubert H. M. Van Tol

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  10. Hyman B. Niznik

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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.Nature350, 614–619 (1991). https://doi.org/10.1038/350614a0

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