Differential stimulation of [3H]MK-801 binding to subpopulations of NMDA receptors.
The potency of L-glutamate in enhancing [3H]MK-801 binding to N-methyl-D-aspartate (NMDA) receptor ion channels was evaluated by quantitative autoradiography. In the presence of saturating concentrations of spermine, glycine and 20 microM D-2-amino-5-phosphonopentanoate (D-AP5), low concentrations of L-glutamate selectively increased [3H]MK-801 binding in the medial striatum and dorsal lateral septum. In comparison to these regions, EC50 values for L-glutamate stimulation of [3H]MK-801 binding were significantly higher in the cerebral cortex and thalamus. Regions displaying greater sensitivity to L-glutamate correlate to those regions where NMDA receptors are preferentially labelled by L-[3H]glutamate; regions less sensitive to L-glutamate correspond to regions selectively labelled by the NMDA antagonist [3H]CPP ([3H]3-((+) -2-carboxypiperazin-4-yl)-propyl-1-phosphonate). Since L-glutamate stimulation of [3H]MK-801 binding appears to reflect channel activation, these results suggest that it is possible to pharmacologically (or pathologically) activate anatomically-distinct subpopulations of NMDA receptors.
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260.
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Monaghan
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D066298:In Vitro Techniques; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D005971:Glutamates; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C056639:2-amino-5-phosphopentanoic acid; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D014633:Valine