Role of glycine in the N-methyl-D-aspartate-mediated neuronal cytotoxicity
| Autor: | Carolann Thompson, Andre I. Salama, William C. Zinkand, Jitendra Patel, Richard A. Keith |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
N-Methylaspartate
Cell Survival Glycine Dibenzocycloheptenes Biology Kynurenic Acid Biochemistry Neuroprotection Piperazines Cellular and Molecular Neuroscience Ion channel complex medicine Serine Animals Glycine receptor Cells Cultured chemistry.chemical_classification Neurons Aspartic Acid Dose-Response Relationship Drug Neurotoxicity Drug Synergism Glycine receptor antagonist medicine.disease Pyrrolidinones Amino acid nervous system chemistry NMDA receptor Dizocilpine Maleate |
| Zdroj: | Journal of neurochemistry. 54(3) |
| ISSN: | 0022-3042 |
| Popis: | 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 strychnine-insensitive glycine site, plays a central permissive role in NMDA-mediated neurotoxicity. |
| Databáze: | OpenAIRE |
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