Figure 2. Signaling pathways elicited by D2R activation.

Canonical G protein-mediated signaling leads to inhibition of adenylyl cyclase (AC) and PKA activity. Activation of βγ subunits results in increased Ca²⁺ and PKC activation, as well as activation of G protein-coupled inwardly rectifying K+ channels (GIRK) and inhibition of voltage-gated Ca²⁺ channels (VGCC). G-protein independent signaling downstream of D2Rs can be mediated by β-arrestin, which inhibits Akt activity to increase GSK-3β function.