Stimulated D1 dopamine receptors couple to multiple Gα proteins in different brain regions

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Abstract
Previous studies have revealed that activation of rat striatal D1 dopamine receptors stimulates both adenylyl cyclase and phospholipase C via Gs and Gq, respectively. The differential distribution of these systems in brain supports the existence of distinct receptor systems. The present communication extends the study by examining other brain regions: hippocampus, amygdala, and frontal cortex. In membrane preparations of these brain regions, selective stimulation of D1 dopamine receptors increases the hydrolysis of phosphatidylinositol/phosphatidylinositol 4,5-biphosphate. In these brain regions, D1 dopamine receptors couple differentially to multiple Gα protein subunits. Antisera against Gαq blocks dopamine-stimulated PIP2 hydrolysis in hippocampal and in striatal membranes. The binding of [35S]GTPγS or [α-32P]GTP to Gαi was enhanced in all brain regions. Dopamine also increased the binding of [35S]GTPγS or [α-32P]GTP to Gαq in these brain regions: hippocampus = amygdala > frontal cortex. However, dopamine-stimulated binding of [35S]GTPγS to Gαs only in the frontal cortex and striatum. This differential coupling profile in the brain regions was not related to a differential regional distribution of the Gα proteins. Dopamine induced increases in GTPγS binding to Gαs and Gαq was blocked by the D1 antagonist SCH23390 but not by D2 receptor antagonist l-sulpiride, suggesting that D1 dopamine receptors couple to both Gαs and Gαq proteins. Co-immunoprecipitation of Gα proteins with receptor-binding sites indicate that in the frontal cortex, D1 dopamine-binding sites are associated with both Gαs and Gαq and, in hippocampus or amygdala, D1 dopamine receptors couple solely to Gαq. The results indicate that in addition to the D1/Gs/adenylyl cyclase system, brain D1-like dopamine receptor sites activate phospholipase C through Gαq protein.