Identification and characterization of a high-affinity glutamate-controlled TCP binding site in rat brain...

The kinetic and equilibrium binding parameters of the phencyclidine receptor ligand [3H]N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) to a postsynaptic density (PSD) subcellular fraction from rat brain were investigated. A single site was found, which was identified as the high-affinity TCP binding site by competition with dibenzocycloalkenimine (MK-801). In contrast, [3H]TCP binds to two sites on the plasma membrane fraction used as a precursor for PSD; on both fractions, [3H]TCP binding responds to glutamate by an increase of the association rate, the dissociation constant and the number of sites being unchanged. In the PSD fraction [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), an antagonist specific for the N-methyl-D-aspartate (NMDA) site, bound to high- and low-affinity sites. These results ascertain the presence and identity of synaptic NMDA-gated ion channels, which are assumed in the current hypothesis about excitotoxicity, long-term potentiation and learning.