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

Previous studies have revealed that activation of rat striatal D-1 dopamine receptors stimulates both adenylyl cyclase and phospholipase C via G(s) and G(q), 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 D-1 dopamine receptors increases the hydrolysis of phosphatidylinositol/phosphatidylinositol 4,5-biphosphate. In these brain regions, D-1 dopamine receptors couple differentially to multiple G alpha protein subunits. Antisera against G alpha (q) blocks dopamine-stimulated PIP2 hydrolysis in hippocampal and in striatal membranes. The binding of [S-35]GTP gammaS or [alpha-P-32]GTP to G alpha (i) was enhanced in all brain regions. Dopamine also increased the binding of [S-35]GTP gammaS or [alpha-P-32]GTP to G alpha (q) in these brain regions: hippocampus = amygdala > frontal cortex. However, dopamine-stimulated binding of [S-35]GTP gammaS to G alphas 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 G alpha proteins. Dopamine induced increases in GTP gammaS binding to G alpha (s) and G alpha (q) was blocked by the D-1 antagonist SCH23390 but not by D-2 receptor antagonist I-sulpiride, suggesting that D-1 dopamine receptors couple to both G alpha (s) and G alpha (q) proteins. Co-immunoprecipitation of G alpha proteins with receptor-binding sites indicate that in the frontal cortex, D-1 dopamine-binding sites are associated with both G alpha (s) and G alpha (q) and, in hippocampus or amygdala, D-1 dopamine receptors couple solely to G alpha (q). The results indicate that in addition to the D-1/G(s)/adenylyl cyclase system, brain D-1-like dopamine receptor sites activate phospholipase C through G alpha (q) protein.