title: Regional distribution and properties of [3H]MK-801 binding sites determined by quantitative autoradiography in rat brain.
abstract: [3H]MK-801 binding in rat brain was characterized using a quantitative autoradiographic binding assay. [3H]MK-801 binding (5 nM) reached equilibrium by 120 min at 23 degrees C. [3H]MK-801 appeared to label a single high affinity site with an affinity constant of approximately 11 nM. [3H]MK-801 binding was heterogeneously distributed throughout the brain with the following order of binding densities: hippocampal formation greater than cortical areas greater than striatum greater than thalamus. Competitive N-methyl-D-aspartate antagonists, DL-2-amino-5-phosphonopentanoic acid, DL-2-amino-7-phosphonoheptanoic acid, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid, and cis-4-phosphonomethyl-2-piperidine carboxylic acid, inhibited [3H]MK-801 binding. Glycine antagonists, 7-chlorokynurenic acid and kynurenic acid, also inhibited [3H]MK-801 binding. Furthermore, the inhibition of [3H]MK-801 binding by the quinoxalinedione compounds 6-cyano-7-nitroquinoxaline-2,3-dione and 6,7-dinitroquinoxaline-2,3-dione was reversed by glycine. [3H]MK-801 binding was also inhibited by zinc ions [3H]MK-801 binding was enhanced by glycine or N-methyl-D-aspartate. These results demonstrate that [3H]MK-801 can be used in a quantitative autoradiographic assay as a functional probe for the N-methyl-D-aspartate receptor complex.
authors.affiliation: Neuroscience Program, University of Michigan, Ann Arbor 48104-1687.
authors.forename: S Y
authors.initials: SY
authors.lastname: Sakurai
authors.forename: J H
authors.initials: JH
authors.lastname: Cha
authors.forename: J B
authors.initials: JB
authors.lastname: Penney
authors.forename: A B
authors.initials: AB
authors.lastname: Young
mesh_terms: D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005998:Glycine / Q000037:antagonists & inhibitors; D007700:Kinetics; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D014316:Tritium; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D005998:Glycine