Document Detail


Dopamine D1 and D2 receptor Co-activation generates a novel phospholipase C-mediated calcium signal.
MedLine Citation:
PMID:  15159403     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although dopamine D1 and D2 receptors belong to distinct subfamilies of dopamine receptors, several lines of evidence indicate that they are functionally linked. However, a mechanism for this linkage has not been elucidated. In this study, we demonstrate that agonist stimulation of co-expressed D1 and D2 receptors resulted in an increase of intracellular calcium levels via a signaling pathway not activated by either receptor alone or when only one of the co-expressed receptors was activated by a selective agonist. Calcium signaling by D1-D2 receptor co-activation was abolished following treatment with a phospholipase C inhibitor but not with pertussis toxin or inhibitors of protein kinase A or protein kinase C, indicating coupling to the G(q) pathway. We also show, by co-immunoprecipitation from rat brain and from cells co-expressing the receptors, that D1 and D2 receptors are part of the same heteromeric protein complex and, by immunohistochemistry, that these receptors are co-expressed and co-localized within neurons of human and rat brain. This demonstration that D1 and D2 receptors have a novel cellular function when co-activated in the same cell represents a significant step toward elucidating the mechanism of the functional link observed between these two receptors in brain.
Authors:
Samuel P Lee; Christopher H So; Asim J Rashid; George Varghese; Regina Cheng; A José Lança; Brian F O'Dowd; Susan R George
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-05-24
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-08-16     Completed Date:  2005-02-15     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  35671-8     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzazepines / pharmacology
Brain / metabolism
Calcium / metabolism
Calcium Signaling* / drug effects
Cell Line
Dopamine Agonists / pharmacology
Estrenes / pharmacology
Humans
Immunohistochemistry
Pyrrolidinones / pharmacology
Quinpirole / pharmacology
Rats
Receptor Cross-Talk*
Receptors, Dopamine D1 / agonists,  metabolism*
Receptors, Dopamine D2 / agonists,  metabolism*
Type C Phospholipases / antagonists & inhibitors,  metabolism*
Chemical
Reg. No./Substance:
0/Benzazepines; 0/Dopamine Agonists; 0/Estrenes; 0/Pyrrolidinones; 0/Receptors, Dopamine D1; 0/Receptors, Dopamine D2; 112648-68-7/1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; 71636-61-8/SK&F 81297; 7440-70-2/Calcium; 85760-74-3/Quinpirole; EC 3.1.4.-/Type C Phospholipases

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