Document Detail

D2 dopamine receptors modulate Galpha-subunit coupling of the CB1 cannabinoid receptor.
MedLine Citation:
PMID:  14634050     Owner:  NLM     Status:  MEDLINE    
CB(1) cannabinoid (CB(1)) and D(2) dopamine (D(2)) receptors are known to couple to the G protein Galpha(i/o). It has been reported that concurrent activation of D(2) receptors and CB(1) receptors, in primary striatal neuronal culture, promotes functional CB(1) receptor coupling to Galpha(s) resulting in elevations in intracellular cyclic AMP levels. We now report that in the absence of D(2) receptors, acute activation of CB(1) receptors inhibits cyclic AMP accumulation, whereas the presence of D(2) receptors promotes CB(1)-stimulated cAMP accumulation, presumably through Galpha(s). This Galpha(s) subunit switching was not prevented by pertussis toxin treatment and occurred in the presence and absence of D(2) receptor activation. Thus, coexpression of the D(2) receptor with the CB(1) receptor was sufficient to switch the coupling of the CB(1) receptors from Galpha(i/o) to Galpha(s). Persistent activation of D(2) receptors resulted in heterologous sensitization of adenylate cyclase to subsequent stimulation by forskolin, whereas the persistent activation of CB(1) receptors did not. Additional studies in human embryonic kidney cells cotransfected with D(2) and CB(1) receptors revealed that persistent activation (18 h) of D(2) receptors induced a switch of CB(1) receptor coupling from Galpha(s) to Galpha(i/o). This D(2) receptor-induced effect allowed for CB(1) receptor-mediated inhibition of cyclic AMP accumulation. The present studies suggest D(2) receptors may have a significant modulatory role in determining the G protein coupling specificity of CB(1) receptors.
A Jarrahian; V J Watts; E L Barker
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-11-21
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  308     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-02-26     Completed Date:  2004-04-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  880-6     Citation Subset:  IM    
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University School of Pharmacy, West Lafayette, IN, USA.
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MeSH Terms
Cells, Cultured
Cyclic AMP / metabolism*
GTP-Binding Protein alpha Subunits / metabolism*
Receptor, Cannabinoid, CB1 / metabolism*
Receptors, Dopamine D2 / metabolism*
Signal Transduction / physiology*
Grant Support
Reg. No./Substance:
0/GTP-Binding Protein alpha Subunits; 0/Receptor, Cannabinoid, CB1; 0/Receptors, Dopamine D2; 60-92-4/Cyclic AMP

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