Non-competitive regulation of phencyclidine/sigma-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/sigma-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/sigma-receptor may be situated in or near a channel regulated by an NMDA receptor complex.