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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

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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.

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Authors and Affiliations

  1. Department of Pediatrics, Drexel University College of Medicine, St. Christopher's Hospital for Children, USA

    David F. Sorrentino, Karen I. Fritz, Syed Hassan Haider, Maria Delivoria Papadopoulos & Om P. Mishra

  2. Department of Pediatrics, University of Texas, Houston, Texas

    Nehal Parikh

Authors
  1. David F. Sorrentino
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  2. Karen I. Fritz
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  3. Syed Hassan Haider
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  4. Nehal Parikh
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  5. Maria Delivoria Papadopoulos
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  6. Om P. Mishra
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Correspondence to David F. Sorrentino.

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Sorrentino, D.F., Fritz, K.I., Haider, S.H. et al. Nitric Oxide–Mediated Modification of the Glycine Binding Site of the NMDA Receptor During Hypoxia in the Cerebral Cortex of the Newborn Piglet. Neurochem Res 29, 455–459 (2004). https://doi.org/10.1023/B:NERE.0000013751.17464.ee

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  • DOI: https://doi.org/10.1023/B:NERE.0000013751.17464.ee

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