J Neurochem. 1990 Mar;54(3):849-54.

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

Patel J, Zinkand WC, Thompson C, Keith R, Salama A.

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Molecular Pharmacology Unit, ICI Americas Inc., Wilmington, DE 19897.

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.

PMID:: 2106010; [PubMed - indexed for MEDLINE]

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