G Proteins Modulate D2 Receptor-Coupled K(ATP) Channels in Rat Dopaminergic Terminals

Abstract

The presynaptic dopamine (DA) D2 receptor-mediated regulation of ATP-sensitive potassium (K⁺_(ATP)) channels was examined in slices of the rat caudate-putamen. When slices were incubated with the specific D2 receptor antagonist (−)-sulpiride (SLP), a concentration-dependent increase of extracellular DA release was observed. SLP-induced enhancement was completely antagonized by coincubation with the K⁺_(ATP) channel opener diazoxide (DIA). Treatment of slices with the D2 receptor agonist quinpirole (QUI) almost completely inhibited DA outflow induced by the K⁺_(ATP) channel blocker butanedione-monoxime (BDM). Coincubation of SLP and guanosine triphosphate (GTP) or its non-hydrolizable analogue guanylyl-5′-imidodiphosphate [Gpp(NH)p], significantly reduced the SLP-induced effect on DA levels. Furthermore, we observed that BDM-induced DA outflow was markedly inhibited by G protein activators suggesting an additional receptor-independent regulation of K⁺_(ATP) channel gating. Our results suggest that PTX-sensitive G proteins are involved in the signal transduction between D2 receptors and K⁺_(ATP) channels. Furthermore, K⁺_(ATP) channels can be modulated in a receptor-independent mechanism by G protein activators.