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PMID:17194762
| Citation |
Rashid, AJ, So, CH, Kong, MM, Furtak, T, El-Ghundi, M, Cheng, R, O'Dowd, BF and George, SR (2007) D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum. Proc. Natl. Acad. Sci. U.S.A. 104:654-9 |
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| Abstract |
We demonstrate a heteromeric D1-D2 dopamine receptor signaling complex in brain that is coupled to Gq/11 and requires agonist binding to both receptors for G protein activation and intracellular calcium release. The D1 agonist SKF83959 was identified as a specific agonist for the heteromer that activated Gq/11 by functioning as a full agonist for the D1 receptor and a high-affinity partial agonist for a pertussis toxin-resistant D2 receptor within the complex. We provide evidence that the D1-D2 signaling complex can be more readily detected in mice that are 8 months in age compared with animals that are 3 months old, suggesting that calcium signaling through the D1-D2 dopamine receptor complex is relevant for function in the postadolescent brain. Activation of Gq/11 through the heteromer increases levels of calcium/calmodulin-dependent protein kinase IIalpha in the nucleus accumbens, unlike activation of Gs/olf-coupled D1 receptors, indicating a mechanism by which D1-D2 dopamine receptor complexes may contribute to synaptic plasticity. |
| Links |
PubMed PMC1766439 Online version:10.1073/pnas.0604049104 |
| Keywords |
Animals; Cell Line; Corpus Striatum/drug effects; Corpus Striatum/metabolism; Dopamine Agonists/pharmacology; Dopamine Antagonists/pharmacology; GTP-Binding Protein alpha Subunits, Gq-G11/metabolism; Humans; Male; Mice; Mice, Knockout; Protein Structure, Quaternary; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1/chemistry; Receptors, Dopamine D1/deficiency; Receptors, Dopamine D1/genetics; Receptors, Dopamine D1/metabolism; Receptors, Dopamine D2/chemistry; Receptors, Dopamine D2/deficiency; Receptors, Dopamine D2/genetics; Receptors, Dopamine D2/metabolism; Signal Transduction |
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Significance
Annotations
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