Excitatory Amino Acids and Hepatic Encephalopathy

  • Roger F. Butterworth
  • Joel Lavoie
  • Christine Peterson
  • Carl W. Cotman
  • John C. Szerb
Chapter
Part of the Experimental Biology and Medicine book series (EBAM, volume 22)

Summary

There is substantial evidence to suggest that glutamate and aspartate are excitatory neurotransmitters in the mammalian central nervous system. Glutamate content of brain is decreased in experimental models of acute and chronic hyperammonemia as well as in autopsied brain tissue from patients dying in hepatic coma resulting from fulminant hepatic failure or cirrhosis. Glutamate-related enzyme changes have also been observed in brain in both experimental and human hepatic encephalopathy. Exposure of hippocampal slices to pathophysiological concentrations of ammonia did not result in significant decreases of K+-stimulated Ca2+-dependent release of glutamate suggesting that the synthesis of neurotransmitter amino acid was not affected in hyperammonemia. However, evoked release of glutamate from hippocampal slices from 4-week portacaval shunted rats was increased 2-fold. Assessment of glutamate receptors by quantitative autoradiography revealed widespread reductions of the N-Methyl-D-Aspartate (NMDA) subclass of receptors. Taken together with the increased glutamate release of in this material, these results suggest that extracellular glutamate (or aspartate) may be increased in sustained hyperammonemia, probably as a result of loss of astrocytic integrity. Such changes could be of pathophysiological significance in hepatic encephalopathy.

Keywords

Urea Pyruvate Glutamine NMDA Alan 

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Copyright information

© The Humana Press Inc. 1989

Authors and Affiliations

  • Roger F. Butterworth
    • 1
  • Joel Lavoie
    • 1
  • Christine Peterson
    • 2
  • Carl W. Cotman
    • 2
  • John C. Szerb
    • 3
  1. 1.Lab. of Neurochem., André-Viallet Clin. Res. CentreHôpital St-LucMontrealCanada
  2. 2.Dept. of PsychobiologyUniv. of CaliforniaIrvineUSA
  3. 3.Dept. of Physiology and BiophysicsDalhousie UniversityHalifaxCanada

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