1991 Fiscal Year Final Research Report Summary
Mitochondrial dysfunction of neuronal cells and impaired metabolism of amino acid neurotransmitters in hepatic encephalopathy
| Project/Area Number |
02454231
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
WATANABE Akiharu Professor, Third Department of Internal Medicine, 医学部内科学第3, 教授 (00033390)
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| Co-Investigator(Kenkyū-buntansha) |
SAITOH Seiji Assistant Professor, Third Department of Internal Medicine, 附属病院第3内科, 講師 (70126522)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Synaptosomes / Neuronal cells / Hepatic encephalopathy / Glutaminase / Ammonia / Neurotransmitter amino acids / Brain stem / GABA |
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| Research Abstract |
The binding of inhibitory and excitatory neurotransmitter amino acids to the synaptosomal membranes from various brain regions such as brain stem was investigated using D-galactosamine-treated rats with fulminant hepatic failure. Furthermore, isolation and primary culture of glial and neuronal cells from normal and liver-injured rats were tried in the present study.
1. The binding study of GABA (inhibitory neurotransmitter) and glutamic acid (excitatory neurotransmitter) to the membrane fraction of neuronal cells uas analysed according to Schafer's method. Although glutamine centents in the synaptosomes of the brain stem increased in hepatic failure rats, the binding of glutamine to the synaptosomal membrane (Km, Vmax) did not change in these rats. There was no alteration of glutamine decarboxylase activity and the binding of GABA to neuronal membranes in hepatic failure rats.
2. Glutaminase activity from the synaptosomal mitochondria was significantly inhibited by ammonia, short chain fatty acids, glutamic acid or GABA, and the data indicate that this might be a kind of feed-back inhibition under the high ammonia state.
3. The isolation of rats glial and neuronal cells was carried out according to the method of Farooq ; the slices of the brain stem was treated by trypsin and separated by the discontinious centrifugation on Ficoll. The cells obtained were microscopically and biochemically similar to the previously reported data. However, primary culture can not be successful, aryd thus further study should be continued with improvement of the culture system. The functional interaction of glia cells and neuronal cells will be further studied.
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