DIFFERENTIAL PROFILES OF BINDING OF A RADIOLABELED AGONIST AND ANTAGONIST AT A GLYCINE RECOGNITION DOMAIN ON THE N-METHYL-D-ASPARTATE RECEPTOR IONOPHORE COMPLEX IN RAT BRAIN

Addition of several polyamines, including spermidine and spermine, was effective in inhibiting binding of the antagonist ligand [H-3]5,7-dic hlorokynurenic acid ([H-3]-DCKA) but not of the agonist ligand [H-3]gl ycine ([H-3]Gly) to a Gly recognition domain on the N-methyl-D-asparti c acid (NMDA) receptor ionophore complex in rat brain synaptic membran es. In contrast, [H-3]DCKA binding was significantly potentiated by ad dition of proposed polyamine antagonists, such as ifenprodil and oroph enyl)-4-[(4-fluorophenyl)methyl]-1-piperidine ethanol, with [H-3]Gly b inding being unchanged. The inhibition by spermidine was significantly prevented by inclusion of ifenprodil. In addition, spermidine signifi cantly attenuated the abilities of four different antagonists at the G ly domain to displace [H-3]DCKA binding virtually without affecting th ose of four different agonists. Phospholipases A(2) and C and p-chloro mercuribenzosulfonic acid were invariably significantly inhibiting [H- 3]DCKA binding with [H-3]Gly binding being unaltered. Moreover, the de nsities of [H-3]DCKA binding were not significantly different from tho se of [H-3]-Gly binding in the hippocampus and cerebral cortex, wherea s the cerebellum had more than a fourfold higher density of [H-3]Gly b inding than of [H-3]DCKA binding. These results suggest that the Gly d omain may have at least two different forms based on the preference to agonists and antagonists in the rodent brain.