Modification of glutamate binding sites in newborn brain during hypoglycemia

Jane E. McGowan, Santina A. Zanelli, Arleen G. Haynes-Laing, Om P. Mishra, Maria Delivoria-Papadopoulos

    Research output: Contribution to journalArticle

    Abstract

    We have shown that acute insulin-induced hypoglycemia leads to specific changes in the cerebral NMDA receptor-associated ion channel in the newborn piglet. The present study tests the hypothesis that exposure to acute hypoglycemia in the newborn will alter the glutamate binding site of both NMDA and kainate receptors. Studies were performed in 3-6 days-old piglets randomized to control (n = 6) or hypoglycemic (n = 6) groups. Hypoglycemia was maintained for 120 min using insulin infusion. Saturation binding assays were performed in cerebral cell membranes using 3H-glutamate or 3H-kainate to determine the characteristics of the glutamate binding sites of the NMDA and kainate receptors, respectively. The concentration of glucose in cerebral cortex was 10-fold less in hypoglycemic piglets than in controls (P <0.05). Brain ATP was not significantly decreased during hypoglycemia, but phosphocreatine decreased from control of 6.6 ± 1.3 μmoles/g brain to 3.2 ± 1.9 μmoles/g brain in hypoglycemic piglets. The Bmax for NMDA-displaceable 3H-glutamate binding was 992 ± 64 fmol/mg protein in hypoglycemic animals, significantly higher than the control value of 746 ± 42 fmol/mg protein. However, the dissociation constant for glutamate was unchanged during hypoglycemia. The 3H-kainate binding studies demonstrated no change in Bmax of high-affinity kainate receptors during hypoglycemia. In contrast, the affinity of the kainate receptor glutamate binding site significantly increased compared to control. Thus, acute hypoglycemia in the newborn piglet had specific effects on the glutamate binding sites of the NMDA and kainate receptors that could be due to alterations in cell membrane lipids or modification of receptor proteins.

    Original languageEnglish (US)
    Pages (from-to)80-86
    Number of pages7
    JournalBrain Research
    Volume927
    Issue number1
    DOIs
    StatePublished - Jan 8 2002

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    Keywords

    • Glutamate receptors
    • Hypoglycemia
    • Kainate
    • Newborn
    • NMDA

    ASJC Scopus subject areas

    • Neuroscience(all)

    Cite this

    McGowan, J. E., Zanelli, S. A., Haynes-Laing, A. G., Mishra, O. P., & Delivoria-Papadopoulos, M. (2002). Modification of glutamate binding sites in newborn brain during hypoglycemia. Brain Research, 927(1), 80-86. https://doi.org/10.1016/S0006-8993(01)03333-9