Dopamine receptors

Five dopamine receptors that have been specified as shown in table are all G-protein coupled receptors and fall into two families. The D₁ family (D₁ and D₅) are coupled to Gs and activate adenylyl cyclase to increase the cAMP synthesis. The family D₂ (D₂, D₃, & D₄) are coupled to Gi and reduce the adenylyl cyclase to decrease the cAMP synthesis.
The D1 receptors are postsynaptic and situated mostly in the striatum and substantia nigra. There are two splice variants of D2. The short variant (D_2S) is an autoreceptor on nigrostriatal and ventral tegmental neurons where it regulate the dopamine synthesis by lowering cAMP concentrations and therefore phosphorylation of tyrosine hydroxylase. The long variant (D_2L) is postsynaptic in the striatum. The D3 receptors are presynaptic autoreceptors and decrease dopamine release by closing the presynaptic Ca²⁺ channels. The D₄ receptors are more abundant in the cortex than striatum. The D₅ receptors are very broadly distributed in the brain.
The Bromocriptine has about 100-fold the affinity for D₂ than D₁ receptors and classic antipsychotic antagonists (example, haloperidol) block postsynaptic D₂ much strongly than D₁ receptors. The Clozapine is a quite selective D4 receptor antagonist.