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Nitric Oxide-mediated Modification of the Glycine Binding Site of the NMDA Receptor During Hypoxia in the Cerebral Cortex of the Newborn Piglet

Overview
Journal Neurochem Res
Specialties Chemistry
Neurology
Date 2004 Mar 9
PMID 15002744
Citations 1
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Abstract

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.

Citing Articles

Effect of 7-nitroindazole sodium on the cellular distribution of neuronal nitric oxide synthase in the cerebral cortex of hypoxic newborn piglets.

Katsetos C, Parikh N, Fritz K, Legido A, Delivoria-Papadopoulos M, Mishra O Neurochem Res. 2006; 31(7):899-906.

PMID: 16804757 DOI: 10.1007/s11064-006-9094-y.

References
1.
Garthwaite J, Charles S, Chess-Williams R . Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature. 1988; 336(6197):385-8. DOI: 10.1038/336385a0. View

2.
Hawkins L, Chazot P, Stephenson F . Biochemical evidence for the co-association of three N-methyl-D-aspartate (NMDA) R2 subunits in recombinant NMDA receptors. J Biol Chem. 1999; 274(38):27211-8. DOI: 10.1074/jbc.274.38.27211. View

3.
Kishimoto H, Simon J, Aprison M . Determination of the equilibrium dissociation constants and number of glycine binding sites in several areas of the rat central nervous system, using a sodium-independent system. J Neurochem. 1981; 37(4):1015-24. DOI: 10.1111/j.1471-4159.1981.tb04489.x. View

4.
Brenman J, Chao D, Gee S, McGee A, Craven S, Santillano D . Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell. 1996; 84(5):757-67. DOI: 10.1016/s0092-8674(00)81053-3. View

5.
Garthwaite J, Beaumont P . Excitatory amino acid receptors in the parallel fibre pathway in rat cerebellar slices. Neurosci Lett. 1989; 107(1-3):151-6. DOI: 10.1016/0304-3940(89)90808-2. View