Role of glycine in the N-methyl-D-aspartate-mediated neuronal cytotoxicity

J Neurochem. 1990 Mar;54(3):849-54. doi: 10.1111/j.1471-4159.1990.tb02329.x.

Abstract

Current evidence indicates that glutamate acting via the N-methyl-D-aspartate (NMDA) receptor/ion channel complex plays a major role in the neuronal degeneration associated with a variety of neurological disorders. In this report the role of glycine in NMDA neurotoxicity was examined. We demonstrate that NMDA-mediated neurotoxicity is markedly potentiated by glycine and other amino acids, e.g., D-serine. Putative glycine antagonists HA-966 and 7-chlorokynurenic acid were highly effective in preventing NMDA neurotoxicity, even in the absence of added glycine. The neuroprotective action of HA-966 and 7-chlorokynurenic acid, but not that of NMDA antagonists 3-(2-carboxypiperazine-4-yl)propylphosphonate and MK-801, could be reversed by glycine. These results indicate that glycine, operating through a strychinine-insensitive glycine site, plays a central permissive role in NMDA-mediated neurotoxicity.

MeSH terms

  • Animals
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / antagonists & inhibitors
  • Aspartic Acid / toxicity
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dibenzocycloheptenes / pharmacology
  • Dizocilpine Maleate
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Glycine / antagonists & inhibitors
  • Glycine / pharmacology
  • Glycine / physiology*
  • Kynurenic Acid / analogs & derivatives
  • Kynurenic Acid / pharmacology
  • N-Methylaspartate
  • Neurons / drug effects*
  • Piperazines / pharmacology
  • Pyrrolidinones / pharmacology
  • Serine / pharmacology

Substances

  • Dibenzocycloheptenes
  • Piperazines
  • Pyrrolidinones
  • Aspartic Acid
  • Serine
  • N-Methylaspartate
  • Dizocilpine Maleate
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • 1-hydroxy-3-amino-2-pyrrolidone
  • Kynurenic Acid
  • 7-chlorokynurenic acid
  • Glycine