NMDA receptor modification during graded hypoxia in the cerebral cortex of newborn piglets.
Previous studies have shown that the cerebral N-methyl-D-aspartate (NMDA) receptor is altered during hypoxia in newborn piglets. The present study tests whether modification of the glutamate and ion channel sites of the NMDA receptor correlates with the progressive decrease in cerebral energy metabolism induced by hypoxia. Degrees of cerebral hypoxia were attained by exposure of ventilated piglets to decreased oxygen at different concentrations and confirmed by tissue phosphocreatine levels. During graded hypoxia, the number of glutamate sites decreased, the affinity of the ion channel site increased, the inhibition by Zn(2+) increased, the activation by glutamate increased, and the activation by glycine decreased. Therefore, modification of the NMDA receptor correlates with the energy state of the tissue. Alterations in receptor phosphorylation may gradually modify the NMDA receptor and may be initiated by subtle decreases in tissue oxygenation in the newborn brain.
Fritz
Karen I
KI
Department of Pediatrics, St. Christopher's Hospital for Children and MCP Hahnemann University, Philadelphia, Pa 19129-1191, USA. Karen.I.Fritz@drexel.edu
Zubrow
Alan B
AB
Mishra
Om P
OP
Delivoria-Papadopoulos
Maria
M
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology; D007473:Ion Channels / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013552:Swine; D015032:Zinc / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D010725:Phosphocreatine; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D015032:Zinc; D005998:Glycine