Different modulation of the binding to two phencyclidine (PCP) receptor subtypes: effects of N-methyl-D-aspartate agonists and antagonists.
Neuroscience letters October 9, 1989 Y Itzhak
The dissociative anesthetics phencyclidine (PCP) and ketamine block the NMDA receptor, a type of excitatory amino acid receptor. This study examined how NMDA receptor activators (agonists) and blockers (antagonists) affect the binding of PCP-like drugs to different sites in rat brain membranes. Glutamate and NMDA (agonists) did not alter binding to the high-affinity sigma/PCP site or the sigma/haloperidol site. However, they increased binding to the low-affinity PCP-selective site by 4- to 5-fold, and this increase was competitively reduced by the antagonist AP-5. The noncompetitive NMDA antagonist MK-801 potently inhibited binding to both the high- and low-affinity sites. These results suggest that the high- and low-affinity PCP binding sites are distinct and are modulated differently by NMDA receptor activity.