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.
Zanelli
S A
SA
Department of Pediatrics, Medical College of Pennsylvania, Hahnemann University and St. Christopher's Hospital for Children, Philadelphia, PA 19129, USA. santina.zanelli@drexel.edu
Ashraf
Q M
QM
Delivoria-Papadopoulos
M
M
Mishra
O P
OP
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics; D005333:Fetus; D018698:Glutamic Acid / Q000493:pharmacokinetics; D006168:Guinea Pigs; D000860:Hypoxia; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D009566:Nitrates / Q000494:pharmacology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*
D007473:Ion Channels; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D009566:Nitrates; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C039642:peroxynitric acid; D018698:Glutamic Acid; D016291:Dizocilpine Maleate