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Role of Glycine in the N ‐Methyl‐d‐Aspartate‐Mediated Neuronal Cytotoxicity
Author(s) -
Patel Jitendra,
Zinkand William C.,
Thompson Carolann,
Keith Richard,
Salama Andre
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb02329.x
Subject(s) - glycine , cytotoxicity , chemistry , neuroscience , biochemistry , stereochemistry , biology , in vitro , amino acid
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.