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

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.

journal_name

J Neurochem

authors

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

doi

10.1111/j.1471-4159.1990.tb02329.x

subject

Has Abstract

pub_date

1990-03-01 00:00:00

pages

849-54

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

54

pub_type

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