Complex allosteric modulation of the binding of the NMDA receptor antagonist [3H]CGP39653.
7-Chlorokynurenate, an antagonist at the glycine recognition site of the NMDA receptor complex, increases the binding of the competitive NMDA receptor antagonist [3H]CGP39653 ([3H]D,L-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid) to well washed rat brain membranes but only in the presence of 100 microM spermine. Conversely, spermine only increases [3H]CGP39653 binding in the presence of 10 microM 7-chlorokynurenate, through a mechanism insensitive to the putative polyamine antagonists ifenprodil, arcaine or putrescine. Thus, the effects of glycine antagonists and polyamines on the binding of competitive NMDA receptor antagonists may depend on the residual glycine and polyamine content of the membrane preparation or the state of the glycine recognition site. These data further attest to the complexity of interactions between spermine and the glycine and glutamate recognition sites of the NMDA receptor.
Oblin
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Department of Preclinical Research, Synthélabo Recherche (L.E.R.S.), Bagneux, France.
Schoemaker
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D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000378:metabolism; D000494:Allosteric Regulation; D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D005998:Glycine / Q000378:metabolism; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D011700:Putrescine / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology
D001645:Biguanides; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C069052:CGP 39653; D013096:Spermine; C006624:arcaine; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid; C010739:ifenprodil; C057013:7-chlorokynurenic acid; D005998:Glycine; D011700:Putrescine