Non-competitive regulation of phencyclidine/σ-receptors by the N-methyl-d-aspartate receptor antagonist d-(-)-2-amino-5-phosphonovaleric acid

d-(-)-2-Amino-5-phosphonovaleric acid (d(-)AP5), a selective, potent competitive antagonist of N-methyl-d-aspartate (NMDA)-type excitatory amino acid receptors was used to investigate the relationship between NMDA receptors and phencyclidine (PCP) binding. Incubation of rat brain membranes with d(-)AP5 decreased the apparent number of PCP/σ-receptors in dose-dependent fashion without affecting their affinity for [2-thienyl-³H]cyclohexylpiperidine (TCP). These data, taken together with electrophysiological evidence that PCP non-competitively antagonizes NMDA receptor-mediated transmission, are consistent with the hypothesis that the PCP/σ-receptor may be situated in or near a channel regulated by an NMDA receptor complex.