[3H]MK‐801 Labels a Site on the N‐Methyl‐D‐Aspartate Receptor Channel Complex in Rat Brain Membranes

摘要: The potent noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist [3H]MK-801 bound with nanomolar affinity to rat brain membranes in a reversible, saturable, and stereospecific manner. of was considerably higher 5 mM Tris-HCl (pH 7.4) than previous studies using Krebs-Henseleit buffer. labels homogeneous population sites cerebral cortical KD 6.3 nM Bmax 2.37 pmol/mg protein. This binding unevenly distributed among regions, hippocampus greater cortex olfactory bulb = striatum medulla-pons, the cerebellum failing show significant binding. Detailed pharmacological characterization indicated site which competitively potently inhibited by known NMDA antagonists, such as phencyclidine, thienylcyclohexylpiperidine (TCP), ketamine, N-allylnormetazocine (SKF 10,047), cyclazocine, etoxadrol, specificity similar labelled [3H]TCP. These were distinct from high-affinity sigma ligand (+)-[3H]SKF 10,047. allosterically modulated endogenous Mg2+ other active divalent cations. data suggest that on channel complex, recognition site, is responsible for blocking action MK-801 antagonists.