INHIBITORY EFFECT OF ETHANOL AND DISULFIRAM ON GABA AMINOTRANSFERASE
| Project/Area Number |
12670410
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Kobe Gakuin University |
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Principal Investigator |
TAMAKI Nanaya KOBE GAKUIN UNIVERSITY, FACULTY OF NUTRITION, PROFESSOR, 栄養学部, 教授 (30068241)
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| Co-Investigator(Kenkyū-buntansha) |
HORIKAWA Yoko KOBE GAKUIN UNIVERSITY, FACULTY OF NUTRITION, RESEARCH TECHNICIAN, 栄養学部, 実験助手 (40309422)
MASUDA Koichi KOBE GAKUIN UNIVERSITY, FACULTY OF NUTRITION, RESEARCH ASSOCIATE, 栄養学部, 助手 (70278795)
SAKATA Sigeko KOBE GAKUIN UNIVERSITY, FACULTY OF NUTRITION, ASSOCIATE PROFESSOR, 栄養学部, 助教授 (30165419)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
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| Keywords | GABA / B-ALANINE / AMINOTRANSFERASE / ANTIALCOHOL DRUG / DISULFIRAM / ETHANOL / ALCOHOL / GABA AMINOTRANSFERASE |
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| Research Abstract |
4-Aminobutyrate (GABA) aminotransferase (β-AlaAT I ; EC 2.6.1.19) activity in the rats is the most active in the brain, followed by the liver and kidney. β-Ala AT I functions mainly in the catabolism of GABA in the brain, and β-alanine, via cytosine and uracil, in the liver and kidney. GABA is a major inhibitory transmitter in many invertebrate systems and in the vertebrate central nervous system. Ethanol has many functions in the brain. It is well recognized that the activity of tyrosine aminotransferase (TAT) increases in response to acute ethanol administration. In this study, we found that a combination of ethanol and disulfiram (N.N.N'.N'-tetraethylthiuram disulfide, an inhibitor of aldehyde dehydrogenase) had an inhibitory effect on (3-AlaAT I yet activated TAT in weanling rats in vivo. The effect on β-AlaAT I was followed by the inhibitory expression of β-AlaAT I mRNA. The β-AlaAT I activity was reduced with a pseudo- first-order profile with time, and the half-life was calculated to be 12.3±0.83 hr with the rate constant (Kd) of 0.056±0.004 hr-l. Neither single intubation of ethanol nor disulfiram affected p-AlaAT I activity for at least 24 hr. A combination of ethanol and pyrazole (1, 2-diazole, an inhibitor of alcohol dehydrogenase) also had no effect on (3- AlaAT I but activated TAT activity. It is well known that disulfiram is degradated to carbon disulfate and diethyamine. However, the intubation with ethanol during the pretreatment of carbon disulfate hadno effect on β-AlaAT I. A combination of ethanol and disulfiram also reduced β-alaninepyruvate minotransferase activity to 60% of the control after 24 hr but the effect was weaker han that on p-AlaAT I.
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Report
(3 results)
Research Products
(10 results)
