Identification of a novel NMDA receptor in rat cerebellum.
Specific binding sites for the noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, [3H]MK-801, were identified in synaptic membranes isolated from rat cerebellum. The density of these sites (0.61 pmol/mg protein), derived from linear Scatchard plots, was lower than those measured in a number of forebrain regions (0.81-2.96 pmol/mg protein). The Kd value for cerebellar [3H]MK-801 binding sites (37.7 nM) was markedly higher than those (1.53-1.82 nM) detected in rat forebrain regions. Experiments were carried out in the presence of 30 microM L-glutamic acid and 1 microM glycine, and after a 210 min incubation [3H]MK-801 binding was maximally stimulated. The pharmacology of these cerebellar [3H]MK-801 binding sites was markedly different from that of [3H]MK-801 sites in the rat cortex. These data have highlighted a novel population of NMDA receptors, which are functionally coupled to an ion channel but exhibit remarkably weak affinity for MK-801.
Department of Organic Chemistry, Royal Danish School of Pharmacy, Copenhagen.
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Ebert
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Wong
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Krogsgaard-Larsen
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism*; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000378:metabolism*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism*
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D005998:Glycine