N-methyl-D-aspartate receptor regulation of uncompetitive antagonist binding in rat brain membranes: kinetic analysis.

摘要: N-Methyl-D-aspartate (NMDA) receptor ligands regulate the binding of uncompetitive antagonists in membranes prepared from rat brain. To determine mechanism this regulation, we examined kinetics radiolabeled antagonist [3H]N-(1-[thienyl]cyclohexyl) piperidine (TCP). Increasing concentrations NMDA agonists produced dose-dependent increases association and dissociation rate constants TCP. The amino phosphono valeric acid virtually abolished both Linear regression analysis detected a significant (p less than 0.001) correlation between effect on apparent constants. most parsimonious explanation data is that TCP by controlling access to transiently accessible or "guarded" site located receptor-coupled ion channel. An increase affinity number sites neither necessary nor sufficient explain potentiation agonists. This finding validates use as measure functional activation channel isolated membrane preparations.