D1-D2 Dopamine Receptor Heterooligomers with Unique Pharmacology Are Coupled to Rapid Activation of Gq/11 in the Striatum

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Dec 30

PMID 17194762

Citations 217

Authors

Asim J Rashid

Christopher H So

Michael M C Kong

Teresa Furtak

Mufida El-Ghundi

Regina Cheng

Brian F ODowd

Susan R George

Affiliations

Soon will be listed here.

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.

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