Peroxynitrite-induced modification of the N-methyl-D-aspartate receptor in the cerebral cortex of the guinea pig fetus at term.

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, (3)H-MK-801 bindings show an increase in the B(max) and a decrease in the K(d), while (3)H-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.