N ‐Methyl‐D‐Aspartate Recognition Site Ligands Modulate Activity at the Coupled Glycine Recognition Site

N ‐Methyl‐D‐Aspartate Recognition Site Ligands Modulate Activity at the Coupled Glycine... Abstract: In synaptic plasma membranes from rat forebrain, the potencies of glycine recognition site agonists and antagonists for modulating (3H)1‐(1‐(2‐thienyl)cyclohexyl)piperidine ((3H)TCP) binding and for displacing strychnine‐insensitive (3H)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 (3H)glycine binding, and the reduction can be fully reversed by the NMDA recognition site agonist, L‐glutamate. Scatchard analysis of (3H)glycine binding shows that in the presence of CGS 19755 there is no change in Bmax (8.81 vs. 8.79 pmol/mg of protein), but rather a decrease in the affinity of glycine (KD of 0.202 γM vs. 0.129 γM). 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 (3H)glycine recognition site increases in the presence of CGS 19755. The functional consequence of this change in affinity was addressed using the modulation of (3H)TCP binding. In the presence of L‐glutamate, the potency of glycine agonists for the stimulation of (3H)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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

N ‐Methyl‐D‐Aspartate Recognition Site Ligands Modulate Activity at the Coupled Glycine Recognition Site

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Publisher
Wiley
Copyright
Copyright © 1990 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1111/j.1471-4159.1990.tb02355.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: In synaptic plasma membranes from rat forebrain, the potencies of glycine recognition site agonists and antagonists for modulating (3H)1‐(1‐(2‐thienyl)cyclohexyl)piperidine ((3H)TCP) binding and for displacing strychnine‐insensitive (3H)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 (3H)glycine binding, and the reduction can be fully reversed by the NMDA recognition site agonist, L‐glutamate. Scatchard analysis of (3H)glycine binding shows that in the presence of CGS 19755 there is no change in Bmax (8.81 vs. 8.79 pmol/mg of protein), but rather a decrease in the affinity of glycine (KD of 0.202 γM vs. 0.129 γM). 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 (3H)glycine recognition site increases in the presence of CGS 19755. The functional consequence of this change in affinity was addressed using the modulation of (3H)TCP binding. In the presence of L‐glutamate, the potency of glycine agonists for the stimulation of (3H)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.

Journal

Journal of NeurochemistryWiley

Published: Mar 1, 1990

References

  • A glycine site associated with N ‐methyl‐D‐aspartic acid receptors: characterization and identification of a new class of antagonists
    Kessler, Kessler; Terramani, Terramani; Lynch, Lynch; Baudry, Baudry
  • Use‐dependent block of excitatory amino acid currents in cultured neurons by ketamine
    MacDonald, MacDonald; Miljkovic, Miljkovic; Pennefather, Pennefather
  • Characterization of a ( 3 H)glycine recognition site as a modulatory site of the N ‐methyl‐D‐aspartate receptor complex
    Monahan, Monahan; Corpus, Corpus; Hood, Hood; Thomas, Thomas; Compton, Compton
  • Cooperative modulation of ( 3 H)MK‐801 binding to the N ‐methyl‐D‐aspartate receptor‐ion channel complex by L‐glutamate, glycine, and polyamines
    Ransom, Ransom; Stec, Stec

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