Complex polyamine effects on [3H]MDL 105,519 binding to the NMDA receptor glycine site.
Several studies have suggested that polyamines modulate the interaction of glycine with the NMDA receptor. We have further investigated the effects of polyamines using the NMDA receptor glycine site antagonist [(E)-3-(2-phenyl-2-carboxyethenyl)-4,6-dichloro-1H-indole-2-carbox ylic acid] ([3H]MDL 105,519). [3H]MDL 105,519 binding assays were performed using well washed membranes prepared from frozen rat brains. The polyamines spermine and spermidine increased the fraction of non-specific binding (determined by the addition of 1 mM glycine) in the [3H]MDL 105,519 binding assay from 40-60% when spermine or spermidine concentration was increased from 1 to 100 microM. Polyamine agonists spermine, spermidine and 1,5-(diethylamino)piperidine (30 microM) did not have a significant effect on displacement of [3H]MDL 105,519 binding by glycine or glycine site antagonists. Similarly, the polyamine antagonist arcaine did not have a significant effect on displacement of [3H]MDL 105,519 binding by glycine or glycine site antagonists. However, spermidine significantly depressed the potency of MDL 105,519 in displacing [3H]dizocilpine binding. These data suggest that [3H]MDL 105,519 may preferentially bind to a polyamine insensitive form of the NMDA receptor.
Department of Pharmacology, University of Pittsburgh, PA 15261, USA.
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D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism*; D005998:Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D007211:Indoles / Q000378:metabolism*; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D014316:Tritium
D000634:Aminoquinolines; D018691:Excitatory Amino Acid Antagonists; D007211:Indoles; C101788:MDL 105519; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; C074617:4-trans-2-carboxy-5,7-dichloro-4-phenylaminocarbonylamino-1,2,3,4-tetrahydroquinoline; D013096:Spermine; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; C066192:5,7-dichlorokynurenic acid; D005998:Glycine; D013095:Spermidine