1988 Fiscal Year Final Research Report Summary
Impaired metabolism of brain stem synaptosomal mitochondria in hepatic encephalopathy
| Project/Area Number |
62570326
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Okayama University Medical School |
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Principal Investigator |
WATANABE Akiharu Associate Professor, First Department of Internal Medicine, Okayama University Medical School, 医学部, 助教授 (00033390)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Hepatic encephalopathy / Hepatic failure / Synaptosome / Ammonia / Neurotransmitter / Amino acid / グルタミナーゼ |
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| Research Abstract |
Glutaminase in the most important enzyme which functions in neurotransmission for supplying both of inhibitory (GABA) and excitatory (glutamic acid) neuro-transmitter amino acids to the neuronal presynaptosome. In the present study, inhibitory effect of ammonia and other neurotoxic substances on phosphate-activated glutaminase activity extracted from the synaptosomal mitochondria of the rat brain stem (medulla oblongata and pons) and cortex was investigated in vitro and in vivo. Ammonium chloride inhibited the glutaminase activity from the mitochondrial synaptosome but not from the non-synaptosome, 0.1 mM and 1 mM ammonium chloride inhibiting to the extent of the remaining activity of 57 to 78%. These ammonia levela sre physiologically expected in the brain in vivo. Other neurotoxic substances such as octanoic acid (0.1 and 1 mM) and methanethiol (1 mM) similarly inhibited the enzyme. However, the enzyme activity from D-galactosa-mine-injured hapatic failure rats was not significantly different from thoseof control rats, suggesting that the inhibition is reversible.
The results suggest that ammonia regulation of neurotransmitter amino acid synthesis at the level of glutaminase in the presynaptosomal mitochondria might be closely related to the pathogenesis of hepatic encephalopathy.
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