Neuroprotective effects of NMDA receptor glycine recognition site antagonism: dependence on glycine concentration.

Published

Journal Article

High-affinity NMDA receptor glycine recognition site antagonists protect brain tissue from ischemic damage. The neuroprotective effect of 5-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021), a selective NMDA receptor antagonist with nanomolar affinity for the glycine binding site, was examined in rat cortical mixed neuronal/glial cultures. ACEA 1021 alone did not alter spontaneous lactate dehydrogenase (LDH) release. Treatment with ACEA 1021 (0.1-10 microM) before 500 microM glutamate, 30 microM NMDA, or 300 microM kainate exposure was found to reduce LDH release in a concentration-dependent fashion. These effects were altered by adding glycine to the medium. Glycine (1 mM) partially reversed the effect of ACEA 1021 on kainate cytotoxicity. Glycine (100 microM-1 mM) completely blocked the effects of ACEA 1021 on glutamate and NMDA cytotoxicity. The glycine concentration that produced a half-maximal potentiation of excitotoxin-induced LDH release in the presence of 1.0 microM ACEA 1021 was similar for glutamate and NMDA (18 +/- 3 and 29 +/- 9 microM, respectively). ACEA 1021 also reduced kainate toxicity in cultures treated with MK-801. The effects of glycine and ACEA 1021 on glutamate-induced LDH release were consistent with a model of simple competitive interaction for the strychnine-insensitive NMDA receptor glycine recognition site, although nonspecific effects at the kainate receptor may be of lesser importance.

Full Text

Duke Authors

Cited Authors

  • Pearlstein, RD; Beirne, JP; Massey, GW; Warner, DS

Published Date

  • May 1998

Published In

Volume / Issue

  • 70 / 5

Start / End Page

  • 2012 - 2019

PubMed ID

  • 9572287

Pubmed Central ID

  • 9572287

International Standard Serial Number (ISSN)

  • 0022-3042

Digital Object Identifier (DOI)

  • 10.1046/j.1471-4159.1998.70052012.x

Language

  • eng

Conference Location

  • England