Glutamate and glycine decrease the affinity of [3H]MK-801 binding in the presence of Mg2+.
The NMDA receptor is coupled to a cation-selective ion channel, which has been implicated in important brain functions such as long-term potentiation and burst firing, and in neuronal death associated with stroke and epilepsy. We have investigated the binding properties of [3H]MK-801, which binds selectively to the open state of the NMDA channel, at physiological concentrations of Mg2+ in membrane preparations of the rat cerebral cortex. Glutamate and glycine were found to enhance [3H]MK-801 binding at low concentrations and inhibit [3H]MK-801 binding at high concentrations. The inhibition of [3H]MK-801 binding was due to an enhancement of the dissociation rate constant and was reversed by competitive glutamate and glycine antagonists. These findings could be explained by a glutamate- and glycine-induced decrease in the affinity of [3H]MK-801 binding sites within activated NMDA channels, in the presence of Mg2+. This decrease in [3H]MK-801 affinity may correspond to a decreased affinity of the site where Mg2+ causes a voltage-dependent block of the NMDA channel.
von Euler
G
G
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Liu
Y
Y
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism
D005971:Glutamates; D007473:Ion Channels; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D008274:Magnesium; D005998:Glycine