Coactivation of D1 and D2 dopamine receptors: in marriage, a case of his, hers, and theirs.

D1 and D2 dopamine receptors exert opposing effects on the same signaling pathway mediated by heterotrimeric GTP-binding proteins. D1 receptor activation positively affects adenylyl cyclase, and D2 receptor activation is either uncoupled from adenylyl cyclase or negatively affects it. These data suggest that coactivation of D1 and D2 receptors should produce opposite or competing intracellular signals through activation of separate D1- and D2-mediated signaling pathways. Unexpectedly, recent research suggests that D1 and D2 receptor coactivation in cells that coexpress both receptors leads to the recruitment of a novel signaling pathway, involving phospholipase C (PLC)-mediated calcium mobilization, that is distinct from the intracellular responses observed after stimulation of either dopamine receptor alone. This observation suggests that stimulation of D1 and D2 dopamine receptors has the potential to give rise to different intracellular signals depending on whether D1 or D2 receptors are activated alone or together.