Ca2+ and H+ antagonize the decrease of [3H]MK-801 binding induced by glutamate and glycine in the presence of Mg2+.
We have studied the effects of various cations on [3H]MK-801 binding to N-methyl-D-aspartate (NMDA) receptors in membrane preparations of the rat cerebral cortex. Low concentrations of Tris, K+, Na+, Mg2+, and Ca2+ enhanced submaximally stimulated [3H]MK-801 binding. At high concentrations, all compounds inhibited [3H]MK-801 binding, possibly by a direct competitive effect. H+ decreased the observed association rate of [3H]MK-801 binding observed as a decreased [3H]MK-801 binding under nonequilibrium conditions, apparently by decreasing the sensitivity of the glutamate and glycine effects on the association rate. In addition, Tris, Na+, Mg2+, and possibly K+ at very high concentrations, permitted glutamate and glycine to decrease [3H]MK-801 binding, probably reflecting a decreased affinity of [3H]MK-801 binding. In contrast, Ca2+ and H+ antagonized these glutamate- and glycine-induced decreases of [3H]MK-801 binding observed in the presence of Mg2+, possibly by a direct competitive action on the permissive Mg2+ effect. These Ca2+ and H(+)-induced increases in [3H]MK-801 binding in the presence of Mg2+ may correspond to an increase in the potency of the Mg2+ block.
Liu
Y
Y
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
von Euler
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G
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D002414:Cations, Monovalent / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology*; D005998:Glycine / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D008959:Models, Neurological; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology
D002413:Cations, Divalent; D002414:Cations, Monovalent; D002712:Chlorides; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D012964:Sodium; D008274:Magnesium; D011188:Potassium; D002118:Calcium; D005998:Glycine