Stimulating and inhibitory effects of the dopamine "stabilizer" (-)-OSU6162 on dopamine D2 receptor function in vitro.
The effect of (-)-OSU6162 on the incorporation of GTPgammaS(35) in the membranes of hD(2l)-transfected CHO cells was investigated. In the absence of dopamine the compound exerted a slight but significant stimulating action, suggesting a weak partial agonism. In the presence of dopamine, low concentrations (10 to 100 nM) enhanced the stimulating action of dopamine. This enhancing effect was reversed by higher concentrations of (-)-OSU6162 in a complex biphasic manner. The dopamine-enhancing action is proposed to be mediated by binding to an allosteric site with high affinity and the inhibitory component by a low-affinity binding to the orthosteric site of the dopamine receptor.
Lahti
R A
RA
Maryland Psychiatric Research Center, University of Maryland, Baltimore, MD, USA.
Tamminga
C A
CA
Carlsson
A
A
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004298:Dopamine / Q000502:physiology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000502:physiology
D065127:Dopamine D2 Receptor Antagonists; D010880:Piperidines; D017448:Receptors, Dopamine D2; C109513:OSU 6162; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004298:Dopamine