(3H)Glycine blinding studies have been performed to further characterize polyamine interactions with the rat brain N‐methyl‐D‐asparate (NMDA) receptor. Strychnine‐insensitive (3H)glycine binding to washed cortical membranes was enhanced by spermine, spermidine, and hirudonin. Spermine stimulation of binding was additive with that produced by the NMDA receptor agonist L‐glutamate. A high concentration of the L‐glutamate antagonist 2‐amino‐5‐phosphonovaleric acid reduced, but did not eliminate, spermine effects. Saturation experiments indicated that L‐glutamate and spermine enhancement of binding was due to an increase in (3H)glycine binding affinity. Kinetic studies showed that optimal concentrations of spermine and L‐glutamate reduced (3H)glycine association and dissociation rates by approximately fivefold and 30‐fold, respectively. In competition experiments, the presence of L‐glutamate and spermine had differential effects on the affinites of compounds that act as either agonists or antagonists at the glycine site of the NMDA receptor. The affinities of the agonists glycine, D‐serine, and Dalanine, were increased about fivefold, while antagonist (HA‐966, 7‐chlorokynurenic acid) inhibitory potencies were unchanged. These data support our previous results showing that the NMDA receptor possesses a novel polyamine recognition site and demonstrate that these compounds directly modulate glycine's interactions with the receptor complex.
Synapse – Wiley
Published: Jan 1, 1990
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