Regulation of the binding of sigma- and phencyclidine (PCP)-receptor ligands in rat brain membranes by guanine nucleotides and ions.

The effect of guanine nucleotides and ions on (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [+ )-[3H]3-PPP), (+)-N-[3H]allylnormetazocine ((+)-[3H]SKF 10047) and [3H]1-[1-(3-hydroxyphenyl)-cyclohexyl]piperidine ([3H]PCP-3-OH) specific binding to rat brain membranes was examined. These 3 compounds are proposed as prototypical ligands for the labeling of the sigma- and phencyclidine (PCP)-receptor subtypes. Competition binding experiments of (+)-SKF 10047 with (+)-[3H]3-PPP yielded a biphasic inhibition curve which transformed to a monophasic curve when membranes were incubated in the presence of Gpp(NH)p (0.1 mM). The common (+)-[3H]3-PPP/(+)-SKF 10047 binding component is more susceptible to Gpp(NH)p than the high affinity [3H]PCP-3-OH/(+)-SKF 10047 common binding component. Low affinity [3H]PCP-3-OH binding, which may represent a PCP-selective site, is not affected by GTP and Gpp(NH)p. Mono- and divalent cations markedly inhibit high affinity [3H]PCP-3-OH binding but they had a differential inhibitory effect on the binding of the other radioligands tested. These findings suggest differences in the regulation of multiple psychotomimetic (sigma- and PCP) binding sites by guanine nucleotides and ions.