Different modulation of the binding to two phencyclidine (PCP) receptor subtypes: Effects of N-methyl-d-aspartate agonists and antagonists

Yossef Itzhak

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Neurochemical studies have indicated that the dissociative anesthetics, phencyclidine (PCP) and ketamine, act as non-competitive antagonists at the excitatory amino acid, N-methyl-d-aspartate (NMDA), receptor-gated ion channel. Since the binding of PCP and related psychotomimetics, i.e. (+)-N-allylnormetazocine ((+)-SKF 10047), in mammalian brain is associated with multiple receptor subtypes, their modulation by NMDA agonists and antagonists was investigated. Binding of the potent PCP analog, [3H]PCP-3-OH to the high-affinity sigma/PCP (σp) site and (+)-[3H]SKF 10047 to the sigma/haloperidol sensitive (σh) site in rat brain membranes was not affected by l-glutamate and NMDA, nor by the competitive NMDA antagonists d-2-amino-5-phosphovaleric acid (AP-5), d-2-amino-7-phosphoheptanoic acid (AP-7). However, binding of [3H]PCP-3-OH to the low-affinity PCP-selective site was enhanced by 4- to 5-fold in the presence of glutamate or NMDA and reduced in a competitive manner by AP-5. The non-competitive NMDA antagonist, MK-801, was however a potent inhibitor of the binding to both σp and PCP sites labeled with [3H]PCP-3-OH. The present results indicate that the high (σp) and low-affinity (PCP) sites, that are distinct from the σh site, are affected differently by NMDA agonists and antagonists, and thus may represent different receptor domains.

Original languageEnglish (US)
Pages (from-to)314-319
Number of pages6
JournalNeuroscience Letters
Volume104
Issue number3
DOIs
StatePublished - Oct 9 1989

Keywords

  • (+)-N-Allylnormetazocine
  • Excitatory amino acid
  • N-Methyl-d-aspartate
  • Phencyclidine
  • Receptor regulation
  • Receptor subtype

ASJC Scopus subject areas

  • Neuroscience(all)

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