COMPLEX POLYAMINE EFFECTS ON [H-3]MDL-105,519 BINDING TO THE NMDA RECEPTOR GLYCINE SITE

Several studies have suggested that polyamines modulate the interactio n of glycine with the NMDA receptor. We have further investigated the effects of polyamines using the NMDA receptor glycine site antagonist arboxyethenyl)-4,6-dichloro-1H-indole-2-carboxylic acid] ([H-3]MDL 105 ,519). [H-3]MDL 105,519 binding assays were performed using well washe d membranes prepared from frozen rat brains. The polyamines spermine a nd spermidine increased the fraction of non-specific binding (determin ed by the addition of 1 mM glycine) in the [H-3]MDL 105,519 binding as say from 40-60% when spermine or spermidine concentration was increase d from 1 to 100 mu M. Polyamine agonists spermine, spermidine and 1,5- (diethylamino)piperidine (30 mu M) did not have a significant effect o n displacement of [H-3]MDL 105,519 binding by glycine or glycine site antagonists. Similarly, the polyamine antagonist arcaine did not have a significant effect on displacement of [H-3]MDL 105,519 binding by gl ycine or glycine site antagonists. However, spermidine significantly d epressed the potency of MDL 105,519 in displacing [H-3]dizocilpine bin ding. These data suggest that [H-3]MDL 105,519 may preferentially bind to a polyamine insensitive form of the NMDA receptor. (C) 1998 Elsevi er Science Ltd. All rights reserved.