Signaling mechanisms of the D3 dopamine receptor

A substantial body of evidence shows the capacity of the dopamine D-3 receptor to couple functionally to G proteins when expressed in an appropriate milieu in heterologous expression systems. In these systems, activation of D-3 receptors inhibits adenylate cyclase, modulates ion flow through potassium and calcium channels, and activates kinases, most notably mitogen-activated protein kinase. Coupling to G(i)/G(o) is implicated in many of these effects, but other G proteins may contribute. Studies with chimeric receptors implicate the third intracellular loop in the mediation of agonist-induced signal transduction. Finally, D-3-preferring drugs modulate expression of c-fos in neuronal cultures and brain. Signaling mechanisms of the D-3 receptor in brain, however, remain to be definitively determined.