title: Characterization of the non-competitive antagonist binding site of the NMDA receptor in dark Agouti rats.
abstract: The ability of non-competitive NMDA antagonists and other selected compounds to inhibit [3H]MK-801 binding to the NMDA receptor in brain membranes was evaluated in female, dark Agouti rats. In homologous competition binding studies the average apparent affinity (KD) of [3H]MK-801 for its binding site was 5.5 nM and the binding site density (Bmax) was 1.83 pmol/mg protein. Inhibition of [3H]MK-801 binding by non-competitive NMDA antagonists was best described with a one-site competition model and the average Hill coefficients were -1. A series of eight non-competitive NMDA antagonists inhibited [3H]MK-801 binding with the following rank order of affinity (K(i), nM): MK-801 (5.5) > dexoxadrol (21.5) > or = TCP (24.2) > phencyclidine (100.8) > (+)-SKF 10,047 (357.7) > dextrorphan (405.2) > ketamine (922.2) > dextromethorphan (2913). These inhibition binding constants determined in dark Agouti rat brain membranes were significantly correlated (P = 0.0002; r2 = 0.95) with previously reported values determined in Sprague-Dawley rats [Wong et al., 1988, J. Neurochem. 50, 274-281]. Despite significant differences in metabolic capability between these strains, the central nervous system NMDA receptor ion channel shares similar characteristics.
authors.affiliation: Program in Neural Sciences, Department of Psychology, Indiana University, 1101 E. 10th Street, Bloomington, IN 47405, USA.
authors.forename: WenLin
authors.initials: W
authors.lastname: Sun
authors.forename: William D
authors.initials: WD
authors.lastname: Wessinger
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D003915:Dextromethorphan / Q000494:pharmacology; D004148:Dioxolanes / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007649:Ketamine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012588:Scintillation Counting; D014316:Tritium
chemical_list: D004148:Dioxolanes; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; C005840:dioxadrol; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D003915:Dextromethorphan; C012134:SK&F 10047; C012058:tenocyclidine; D010620:Phenazocine; D010622:Phencyclidine; C579650:dexoxadrol