1999 Fiscal Year Final Research Report Summary
Structures and Function of Novel Esterase and Amidohydrolase
| Project/Area Number |
10672067
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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 |
Biological pharmacy
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| Research Institution | Hokuriku University |
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Principal Investigator |
WATANABE Kazuhito Hokuriku University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30113038)
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| Co-Investigator(Kenkyū-buntansha) |
USAMI Noriyuki Gifu Pharmaceutical University, 薬学部, 助手 (60257483)
MATSUNAGA Tamihide Hokuriku University, Faculty of Pharmaceutical Sciences, Lecturer Research Associate, 薬学部, 講師 (40209581)
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| Project Period (FY) |
1998 – 1999
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| Keywords | cannabinoid / ES46.5K / anandamide amidohydrolase / substrate specificity / cloning / antibody / cross-tolerance / interaction |
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| Research Abstract |
1) ES46.5K, a novel esterase, hydrolyzed stereospecifically and regioselectively the acetyl derivatives of tetrahydrocannabinol (THC) metabolites.
2) ES46.5K could hydrolze acetylaminofluorene, phthalate esters, cocaine and heroin, suggesting that the enzyme has some role for metabolizing enzyme of xenobiotic esters.
3) cDNA cloning of ES46.5K is in progress using cDNA of human AAF-DAC as a probe.
4) Natural cannabinoids (THC, cannabidiol, cannabinol) and some of THC metabolites inhibited anandamide amidohydrolase in mouse brain microsomes.
5) Anandamide amidohydrolase was purified from mouse hepatic microsomes and characterized its properties. It is demonstrated that the enzyme has an important role for regulation of biological effects of anandamide.
6) The antibody against anandamide amidohydrolase was prepared.
7) The Antibody-reactive clones were obtained by screening of cDNA library from mouse liver.
8) Tolerance and cross-tolerance developed in the cataleptogenic and hypothermic effect of THC, THC metabolites and anandamide. Pharmacologic interaction between the cannabinoids and anandamide was also demonstrated.
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