G proteins modulate D2 receptor-coupled K(ATP) channels in rat dopaminergic terminals.
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.
Neusch
C
C
California Institute of Technology, Division of Biology, Pasadena 91125, USA. neusch@caltech.edu
Runde
D
D
Moser
A
A
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D008024:Ligands; D009411:Nerve Endings / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018492:Dopamine Antagonists; D008024:Ligands; D015221:Potassium Channels; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; D013469:Sulpiride; D000255:Adenosine Triphosphate; D019204:GTP-Binding Proteins; D004298:Dopamine