In vitro and in vivo characterization of the NMDA receptor-linked strychnine-insensitive glycine site

B W Peeters, P M Vanderheyden

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13 Citations (Scopus)

Abstract

Modulation of the NMDA receptor by the strychnine-insensitive glycine site was studied both in vitro and in vivo. In vitro the glycinergic stimulation of [3H]MK801 binding was measured in three different rat forebrain membrane preparations. An increased association rate of [3H]MK801 in the presence of glycine was observed. The binding of the radioligand was also enhanced by D-serine, whereas L-serine was less potent. The concentration-effect curves were shifted to the right by the glycine antagonist 7-chlorokynurenic acid (7CKA). In vivo modulation of the N-methyl-D-aspartate (NMDA) receptor was studied using NMDA induced convulsions in 7 day old rats. The NMDA effect was blocked by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten,5,10-imine maleate (MK801) and D-(-)-2-amino-5-phosphono-pentanoic acid (AP5). The effect of a submaximal dose of NMDA was dose-dependently potentiated by 1-10 mg/kg D-serine, whereas higher doses of L-serine were needed to obtain a similar effect. 7CKA did not affect NMDA-induced convulsions but reduced the D-serine potentiation of NMDA responses. This study illustrates the ability of the strychnine-insensitive glycine site to modulate the NMDA receptor function both in vitro and in vivo.

Original languageEnglish
Pages (from-to)157-162
Number of pages6
JournalEpilepsy Research
Volume12
Issue number2
Publication statusPublished - Jul 1992

Keywords

  • 2-Amino-5-phosphonovalerate
  • Animals
  • Animals, Newborn
  • Dizocilpine Maleate
  • Glycine
  • Kynurenic Acid
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate
  • Seizures
  • Serine
  • Stereoisomerism
  • Strychnine

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