Nitric oxide-mediated modification of the glycine binding site of the NMDA receptor during hypoxia in the cerebral cortex of the newborn piglet.
This study tested the hypothesis that cerebral hypoxia results in nitric oxide (NO)-mediated modification of the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor. Glycine binding characteristics were determined in normoxic, hypoxic, and hypoxic with 7-nitroindazole (7-NINA)-pretreated newborn piglets. The role of nitration was evaluated by determining binding characteristics in non-nitrated and in-vitro nitrated membranes. Bmax and Kd values were 30% higher in the hypoxic group than the normoxic and 7-NINA pretreated hypoxic groups. Kd values in the in-vitro normoxic nitrated membranes were similar to the non-nitrated hypoxic group. Bmax values in the in-vitro) normoxic nitrated membrane samples were 16% lower than in the non-nitrated hypoxic group. We conclude cerebral hypoxia causes modification of the glycine-binding site of the NMDA receptor and this modification of the glycine-binding site may be NO mediated. We propose that NO-mediated modification of the glycine-binding site of the NMDA receptor regulates calcium influx through its ion-channel.
Sorrentino
David F
DF
Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, USA. Ductusarteriosus@hotmail.com
Fritz
Karen I
KI
Haider
Syed Hassan
SH
Parikh
Nehal
N
Papadopoulos
Maria Delivoria
MD
Mishra
Om P
OP
D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005998:Glycine / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013552:Swine
D004791:Enzyme Inhibitors; D007191:Indazoles; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005998:Glycine; C080122:7-nitroindazole