TY - JOUR T1 - Multiple sites for the regulation of the N-methyl-D-aspartate receptor. JF - Molecular Pharmacology JO - Mol Pharmacol SP - 581 LP - 584 VL - 33 IS - 6 AU - I J Reynolds AU - R J Miller Y1 - 1988/06/01 UR - http://molpharm.aspetjournals.org/content/33/6/581.abstract N2 - The N-methyl-D-aspartate (NMDA) receptor consists of a recognition site for NMDA, a cation-selective ion channel, and binding sites for glycine, Zn2+, and phencyclidine-like compounds. In addition, the channel can be blocked by Mg2+. We have studied the NMDA receptor using the potent and specific phencyclidine-like compound [3H]MK-801. Drugs that bind to the NMDA, glycine, Zn2+, and Mg2+ recognition sites profoundly affect both the association and the dissociation rate of [3H]MK-801. NMDA-like agonists, glycine, and Mg2+ all increase the rates of association and dissociation of [3H]MK-801, whereas the NMDA antagonists AP5 and Zn2+ decrease these rates. These data allow the construction of a model of drug interaction at the NMDA receptor that is based on the binding of MK-801 within the NMDA-operated channel. Using this model it is possible to clearly distinguish between drug action at any of the five binding sites proposed. ER -