Abstract
The effect of guanine nucleotides and ions on
(+)-[
3
H]3-(3-
hydroxyphenyl)-N-(1-
propyl)
piperidine
((+)-[
3H]3-PPP),
(+)-N-[
3
H]
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 σ- 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
(+)-[
3
H]3-
PPP/(+)-
SKF 10047
binding component is more susceptible to Gpp(NH)p than the high affinity
[
3
H]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 (σ- and PCP) binding sites by guanine nucleotides and ions.
