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1998 Fiscal Year Final Research Report Summary

Biosynthesis and metabolism of anandamide as an endogenous ligand for cannabinoid receptors

Research Project

Project/Area Number 08308036
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionThe University of Tokushima

Principal Investigator

YAMAMOTO Shozo  The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (50025607)

Co-Investigator(Kenkyū-buntansha) MIYAMOTO Tsumoru  Japan Tobacco Inc., Central Pharmaceutical Research Institute, Biology Institute, 所長(研究職)
IMAI Kazuhiro  University of Tokyo, Graduate School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (50012620)
WAKU Keizo  Teikyo University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (90013854)
YAMAMOTO Ikuo  Hokuriku University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (50069746)
KUDO Ichiro  Showa University, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (30134612)
Project Period (FY) 1996 – 1998
KeywordsCannabinoid / Marijuana / Anandamide / 2-Arachidonoylglycerol / Arachidonic acid / Endocannabinoid / Receptor / Hydrolase
Research Abstract

Specific receptors for cannabinoids were earlier found in brain (CB1) and peripheral tissues (CB2). As endogenous ligands for these receptors, arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) were recently identified, and they are now under active investigations. The purpose of this research project is to study on the biosynthesis and metabolism of these endocannabinoids together with the developments of their assays and receptor agonists and antagonists. The following experimental results have been reported by individual members of the research group.
1) Studies on the enzymes : Anandamide amidohydrolase which hydrolyzed anandamide and lost its biological activities was found in brain and liver. The porcine brain enzyme was partially purified by S.Yamamoto et al., who demonstrated a broad substrate specificity and the reversibility of the enzyme reaction. The anandamide synthesis from arachidonic acid and ethanolamine was confirmed with a rat recombinant enzyme. It should be noted that the same enzyme hydrolyzes 2-AG.It was reported by I.Yamamoto et al. that the enzyme was inhibited by various cannabinoids. Because of a high Km for ethanolamine, the physiological role of the reverse reaction of anandamide amidohydrolase is questionable. The particifation of phospholipase D was suggested by Waku et al. and Kudo et al. to hydrolyze N-arachidonoylphosphatidy lethanolamine releasing anandamide.
2) Development of anandamide assay : A sensitive HPLC method was developed for fluorescent derivative of anandamide. GC-MS analysis was also performed with anandamide.
3) Studies on biological activities : Waku et al. identified 2-AG as another endogenous ligand for CB1, and studied its structure-activity relationship as CB1 ligand. Kudo et al. found the inhibitory activity of anandamide on the collagen-induced aggregation of platelets. New agonists for CB2 without effect on CB1 were developed by Miyamoto et al..

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] T.Sugiura: "Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor:structure-activity relationship of 2-arachidonoylglycerol,ether-linked analogues and related compopunds" J.Biol.Chem.274. 2794-2801 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Kimura: "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(和文)」より
  • [Publications] S.K.Goparaju: "Anandamide amidohydrolase reacting with 2-arachidonoylglycerol,another cannabinoid receptor ligand" FEBS Lett.422. 69-73 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y.Kurahashi: "Reversible hydrolysis and synthesis of anandamide demonstrated by recombinant rat fatty-acid amide hydrolase" Biochem.Biophys.Res.Commun.237. 512-515 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] D.Koga: "Liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric determination of anandamide and its analogs in rat brain and peripheral tissues" J.Chromatogr.B. 690. 7-13 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Sugiura: "2-Arachidonoylglycerol,a putative endogenous cannabinoid receptor ligand,induces rapid,transient elevation of intracellular free Ca^<2+> in neuroblastoma x glioma hybrid NG108-15 cells" Biochem.Biophys.Res.Commun.229. 58-64 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Sugiura et al.: "Evidence that the cannabinoid CB receptor is a 2-arachidonoylglycerol receptor : structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues and related compopunds" J.Bio1. Chem.274. 2794-2801 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kimura et al.: "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
  • [Publications] S.K.Goparaju et al.: "Anandamide amidohydrolase reacting with 2-arachidonoylglycerol, another cannabinoid receptor ligand" FEBS Letft.422. 69-73 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Kurahashi et al.: "Reversible hydrolysis and synthesis of anandamide demonstrated by recombinant rat fatty-acid amide hydrolase" Biochem. Biophys. Res. Commun.237. 512-515 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] D.Koga et al.: "Liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric determination of anandamide and its analogs in rat brain and peripheral tissues" J.Chromatogr. B. 690. 7-13 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Sugiura et al.: "2-Arachidonoylglycerol, a putative endogenous cannabinoid receptor ligand, induces rapid, transient elevation of intracellular free Ca_+ in neuroblastoma x glioma hybrid NG108-15 cells" Biochem. Biophys. Res. Commun.229. 58-64 (1996)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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