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Structures and Function of Novel Esterase and Amidohydrolase

Research Project

Project/Area Number 10672067
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionHokuriku University

Principal Investigator

WATANABE Kazuhito  Hokuriku University, Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (30113038)

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)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordscannabinoid / ES46.5K / anandamide amidohydrolase / substrate specificity / cloning / antibody / cross-tolerance / interaction / anandamide / エステラーゼ
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.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] N.Usami, K.Kobana, H.Yoshida, T.Kimura, K.Watanabe, H.Yoshimura and I.Yamamoto: "Synthesis and pharmacological activities in mice of halogenated D^9-tetrahydrocannabinol derivatives"Chem. Pharm. Bull.. 46. 1462-1467 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Kimura, T.Ohta, K.Watanabe, H.Yoshimura and I.Yamamoto: "Anandamide, an endogenous cannabinoid receptor ligand, also interacts with 5-hydroxy-tryptamine (5-HT) receptor"Biol. Pharm. Bull.. 21. 224-226 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] I.Yamamoto, T.Kimura, A.Kamei, H.Yoshida, K.Watanabe, I.K.Ho and H.Yoshida: "Competitive inhibition of D^8-tetrahydrocannabinol and its active metabolites for cannabinoid receptor binding"Biol. Pharm. Bull.. 21. 408-410 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Watanabe, H.Ogi, S.Nakamura, Y.Kayano, T.Matsunaga, H.Yoshimura and I.Yamamoto: "Distribution and characterization of anandamide amidohydrolase in mouse brain and liver"Life Sci.. 62. 1223-1229 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Watanabe, H.Ogi, S.Nakamura, T.Kimura, I.K.Ho, H.Yoshimura and I.Yamamoto: "Pharmacological effects in mice of anandamide and its related fatty acid ethanolamides, and enhancement of cataleptogenic effect of anandamide by phenylmethylsulfonylfluride"Biol. Pharm. Bull.. 22. 366-370 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Usami, T. Okuda, H.Yoshida, T.Kimura, K.Watanabe, H.Yoshimura and I.Yamamoto: "Synthesis and pharmacological effects in mice of halogenated cannabidiol derivatives"Chem. Pharm. Bull.. 47. 1641-1645 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Usami, K.Kobana, H.Yoshida, T.Kimura, K.Watanabe, H.Yohsimura and I.Yamamoto: "Synthesis and pharmacological activities in mice of halogenated delta-9-tetrahydrocannabinol"Chem.Pharm.Bull. 46. 1462-1467 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Kimura, T.Ohta, K.Watanabe, H.Yoshimura and I.Yamamoto: "Anandamide, an endogenous cannabinoid receptor ligand, also interacts with 5-hydroxytryptamine (5-HT) receptor"Biol.Pharm.Bull. 21. 224-226 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] I.Yamamoto, T.Kimura, A.Kamei, H.Yoshida, K.Watanabe, I.K.Ho and H.Yoshimura: "Competitive inhibition of delta-8-tetrahydrocannabinol and its active metabolites for cannabinoid"Biol.Pharm.Bull.. 408-410 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Watanabe, H.Ogi, S.Nakamura, Y.Kayano, T.Matsunaga, H.Yoshimura and I.Yamamoto: "Distribution and characterization of anandamide amidohydrolase in mouse brain and liver"Life Sci.. 1223-1229 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Watanabe, T.Matsunaga, S.Nakamura, T.Kimura, I.K.Ho, H.Yoshimura and I.Yamamoto: "Pharmacological effects in mice of anandamide and its related fatty acid ethanolamides, and enhancement of cataleptogenic effect of anandamide by phenylmethylsulfonylfluride"Biol.Pharm.Bull.. 22. 366-370 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Usami, T.Okuda, H.Yoshida, T.Kimura, K.Watanabe, H.Yoshimura and I.Yamamoto: "Synthesis and pharmacological effects in mice of halogenated cannabidiol derivatives"Chem.Pharm.Bull.. 47. 1641-1645 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Watanabe et al.: "Pharmacological effectcs in mice of anandamide and its related ethanolamides, and enhancement of cataleptogenic effect of anandamide by PMSF"Biol. Pharm. Bull.. 22. 366-370 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N. Usami et al.: "Synthesis and pharmacological evaluation in mice of halogenated cannabidiol derivatives"Chem. Pharm. Bull.. 47. 1641-1645 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N. Usami et al.: "inhibition of mouse hepatic glutathione S-tranferase by delta-8-tetrahydro-cannabinol p- quinone and cannabidiol-hydroxy quinone"Res. Commun. Alcohol Subst. Abuse. 20. 53-68 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N. Usami et al.: "Generation of reactive oxygen species during mouse hepatic microsomal metabolism of cannabidiol and cannabidiol hydroxy-quinone"Res. Commun. Alcohol Subst. Abuse. ( in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Watanabe et al.: "Distribution and characterization of anandamide amidohhydrolase in mouse brain and liver" Life Sci.62. 1223-1229 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Kimura et al.: "Aanandamide, an endogenous cannabinoid receptor ligand, also interacts with 5-hydroxytryptamine (5-HT) receptor" Biol.Pharm.Bull.21. 224-226 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] I.Yamamoto et al.: "Competitive inhibition of △^8-tetrahydrocannabinol and its active metabolites for cannabinoid receptor binding" Biol.Pharm.Bull.21. 408-410 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Usami et al.: "Synthesis and pharmacological activities in mice of halogenated △^9-tetrahydrocannabinol derivatives" Chem.Pharm.Bull.46. 1462-1467 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Watanabe et al.: "Pharmacological effects in mice of anandamide and its related ethanolamides, and enhancement of cataleptogenic effect of ----." Biol.Pharm.Bull.22(in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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