Functional Analysis of the Human D2 Dopamine Receptor Missense Variants
The human dopamine D 2 receptor gene ( DRD2 ) has three polymorphic variants that predict the amino acid substitutions Val 96 â Ala, Pro 310 â Ser, and Ser 311 â Cys in the receptor protein. We have investigated the ligand binding and signal transduction properties of these human D 2 receptor...
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Published in | The Journal of biological chemistry Vol. 271; no. 42; pp. 26013 - 26017 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
18.10.1996
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Subjects | |
Online Access | Get full text |
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Summary: | The human dopamine D 2 receptor gene ( DRD2 ) has three polymorphic variants that predict the amino acid substitutions Val 96 â Ala, Pro 310 â Ser, and Ser 311 â Cys in the receptor protein. We have investigated the ligand binding and signal transduction properties of these human
D 2 receptor variants by stably expressing them in cultured mammalian cells. The Cys 311 and Ser 310 variants of the human D 2 receptor, which involve substitutions located in the third cytoplasmic loop, were markedly less effective in inhibiting cAMP
synthesis than the most prevalent form (Pro 310 , Ser 311 ). Despite this difference, the Cys 311 and Ser 310 variants couple to G proteins in CHO-K1 (Chinese hamster ovary) cells. The impairment of the Cys 311 and Ser 310 variants to inhibit cAMP levels thus appears to result from a reduced ability of those variant receptors to activate the
appropriate G i -like protein. The demonstration of substantial functional differences between DRD2 gene variants found in the human population might have important pharmacological implications given the widespread use of
D 2 receptor blocking drugs in the treatment of schizophrenia and other psychiatric disorders. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.271.42.26013 |