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N ‐Methyl‐D‐Aspartate Recognition Site Ligands Modulate Activity at the Coupled Glycine Recognition Site
Author(s) -
Hood William F.,
Compton Robert P.,
Monahan Joseph B.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb02355.x
Subject(s) - nmda receptor , glycine , chemistry , strychnine , binding site , agonist , stereochemistry , amino acid , biochemistry , receptor
In synaptic plasma membranes from rat forebrain, the potencies of glycine recognition site agonists and antagonists for modulating [ 3 H]1‐[1‐(2‐thienyl)cyclohexyl]piperidine ([ 3 H]TCP) binding and for displacing strychnine‐insensitive [ 3 H]glycine binding are altered in the presence of N ‐methyl‐D‐aspartate (NMDA) recognition site ligands. The NMDA competitive antagonist, cis ‐4‐phosphonomethyl‐2‐piperidine carboxylate (CGS 19755), reduces [ 3 H]glycine binding, and the reduction can be fully reversed by the NMDA recognition site agonist, L‐glutamate. Scatchard analysis of [ 3 H]glycine binding shows that in the presence of CGS 19755 there is no change in B max (8.81 vs. 8.79 pmol/mg of protein), but rather a decrease in the affinity of glycine ( K D of 0.202 γ M vs. 0.129 γ M ). Similar decreases in affinity are observed for the glycine site agonists, D‐serine and 1‐aminocyclopropane‐1‐carboxylate, in the presence of CGS 19755. In contrast, the affinity of glycine antagonists, 1‐hydroxy‐3‐amino‐2‐pyrrolidone and 1‐aminocyclobutane‐1‐carboxylate, at this [ 3 H]glycine recognition site increases in the presence of CGS 19755. The functional consequence of this change in affinity was addressed using the modulation of [ 3 H]TCP binding. In the presence of L‐glutamate, the potency of glycine agonists for the stimulation of [ 3 H]TCP binding increases, whereas the potency of glycine antagonists decreases. These data are consistent with NMDA recognition site ligands, through their interactions at the NMDA recognition site, modulating activity at the associated glycine recognition site.