Inhibitory modulation by sodium ions of the N-methyl-D-aspartate recognition site in brain synaptic membranes.
Specific binding of radiolabeled L-glutamic acid (Glu) was examined using rat brain synaptic membranes treated with a low concentration of Triton X-100. The binding drastically increased in proportion to increasing concentrations of the detergent used up to 0.1%. Addition of 100 mM sodium acetate significantly potentiated the binding in membranes not treated with Triton X-100, whereas it markedly inhibited the binding in Triton-treated membranes. The binding in Triton-treated membranes was inversely dependent on incubation temperature and reached a plateau within 10 min after the initiation of incubation at 2 degrees C, whereas the time required to attain equilibrium at 30 degrees C was less than 1 min. Sodium acetate invariably inhibited the binding detected at both temperatures independently of the incubation time via decreasing the affinity for the ligand. The binding was significantly displaced by agonists and antagonists for an N-methyl-D-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid receptors, but not by those for the other subclasses. Inclusion of sodium acetate reduced the potencies of NMDA agonists to displace the binding without virtually affecting those of NMDA antagonists. Moreover, sodium ions inhibited the ability of Glu to potentiate the binding of N-[3H] [1-(2-thienyl)cyclohexyl]piperidine to open NMDA channels in Triton-treated membranes. These results suggest that sodium ions may play an additional modulatory role in the termination process of neurotransmission mediated by excitatory amino acids via facilitating a transformation of the NMDA recognition site from a state with high affinity for agonists to a state with low affinity.
Department of Pharmacology, Setsunan University, Osaka, Japan.
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Yoneda
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Ogita
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D003902:Detergents / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007477:Ions; D007700:Kinetics; D008297:Male; D017830:Octoxynol; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012964:Sodium / Q000494:pharmacology*; D013570:Synaptic Membranes / Q000378:metabolism*
D003902:Detergents; D005971:Glutamates; D007477:Ions; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D011092:Polyethylene Glycols; C012058:tenocyclidine; D017830:Octoxynol; D012964:Sodium; D010622:Phencyclidine