Journal
NEUROSCIENCE LETTERS
Volume 296, Issue 1, Pages 5-8Publisher
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0304-3940(00)01608-6
Keywords
N-methyl-D-aspartate receptor; peroxynitrite; brain; hypoxia; fetus; nitrotyrosine
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Funding
- NICHD NIH HHS [HD-20337, HD-38079] Funding Source: Medline
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The present study tests the hypothesis that nitration is a potential mechanism of N-methyl-D-aspartate (NMDA) receptor modification, by assessing the effect of peroxynitrite in vitro on the glutamate and ion-channel sites of the NMDA receptor in the fetal guinea pig. Nitration of NMDA receptor subunits was confirmed by Western blot. Following peroxynitrite exposure, H-3-MK-801 bindings show an increase in the B-max and a decrease in the K-d, while H-3-glutamate bindings show a decrease in the K-d with no change in the B-max. We conclude that peroxynitrite regulates the NMDA receptor function by increasing the affinity of the ion-channel and glutamate sites, and by exposing additional ion-channel sites. We propose that nitration of the NMDA receptor is a potential mechanism for the regulation of the receptor during hypoxia. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
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