title: Regulation of the binding of sigma- and phencyclidine (PCP)-receptor ligands in rat brain membranes by guanine nucleotides and ions.
abstract: 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.
authors.affiliation: Department of Pharmacology, Hadassah School of Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Itzhak
authors.forename: M
authors.initials: M
authors.lastname: Khouri
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002412:Cations; D006150:Guanine Nucleotides / Q000494:pharmacology*; D008297:Male; D010620:Phenazocine / Q000031:analogs & derivatives / Q000378:metabolism; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D002412:Cations; D006150:Guanine Nucleotides; D010880:Piperidines; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; C012134:SK&F 10047; C033114:3-hydroxyphencyclidine; C026539:preclamol; D010620:Phenazocine; D010622:Phencyclidine