Differential Profiles of Binding of a Radiolabeled Agonist and Antagonist at a Glycine Recognition Domain on the N‐ Methyl‐D‐Aspartate Receptor lonophore Complex in Rat Brain

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Abstract
Addition of several polyamines, including spermidine and spermine, was effective in inhibiting binding of the antagonist ligand [3H] 5, 7‐dichlorokynurenic acid ([3H]‐ DCKA) but not of the agonist ligand [3H] glycine ([3H] Gly) to a Gly recognition domain on the N‐methyl‐D‐aspartic acid (NMDA) receptor ionophore complex in rat brain synaptic membranes. In contrast, [3H] DCKA binding was significantly potentiated by addition of proposed polyamine antagonists, such as ifenprodil and (±)‐α‐(4‐chlorophenyl)‐4‐ [(4‐fluorophenyl)methyl]‐1‐piperidine ethanol, with [3H] Gly binding being unchanged. The inhibition by spermidine was significantly prevented by inclusion of ifenprodil. In addition, spermidine significantly attenuated the abilities of four different antagonists at the Gly domain to displace [3H] DCKA binding virtually without affecting those of four different agonists. Phospholipases A2 and C and p‐chloromercuribenzosulfonic acid were invariably effective in significantly inhibiting [3H] DCKA binding with [3H] Gly binding being unaltered. Moreover, the densities of [3H] DCKA binding were not significantly different from those of [3H]‐ Gly binding in the hippocampus and cerebral cortex, whereas the cerebellum had more than a fourfold higher density of [3H] Gly binding than of [3H] DCKA binding. These results suggest that the Gly domain may have at least two different forms based on the preference to agonists and antagonists in the rodent brain.

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