Kinetic characterization of the phencyclidine-N-methyl-D-aspartate receptor interaction: evidence for a steric blockade of the channel.
Biochemistry February 9, 1988 Y Kloog, R Haring, M Sokolovsky
The binding of a PCP-site ligand ([3H]TCP) to NMDA receptors in rat brain membranes is slow unless glutamate and glycine are present. Without these agonists, association and dissociation take hours; with them, both accelerate dramatically (dissociation half-life drops from ~128–165 min to ~8 min). The competitive NMDA antagonist AP-5 blocks this acceleration. The authors propose a two-step model: the ligand must cross a barrier—likely the closed NMDA receptor channel—that opens when agonists bind.