1997 Fiscal Year Final Research Report Summary
Biosynthesis and metabolism of cannabimimetic anandamide
| Project/Area Number |
09044313
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Pathological medical chemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YAMAMOTO Shozo The University of Tokushima, School of Medicine Department of Biochemistry, Professor, 医学部, 教授 (50025607)
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| Co-Investigator(Kenkyū-buntansha) |
PIOMELLI Daniele The Neuroscience Institute, California, U.S.A., Senior fellow, カリフォルニア州・サンディエゴ神経科学研究所, 主任研究員
GERWICK William Oregon State University, College of Pharmacy, Oregon, U.S.A., Professor, オレゴン州立大学・薬学部, 教授
MARZO Vincenzo di Consiglio Nationale delle Ricerche Instituto per la Chimica di Molecole di Inter, 国立ナポリ生体分子化学研究所, 研究助手
UEDA Natsuo The University of Tokushima, School of Medicine Department of Biochemistry, Asso, 医学部, 助教授 (20193807)
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| Project Period (FY) |
1997
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| Keywords | Anandamide / Cannabinoid / Marijuana / Arachidonoylethanolamide / Arachidonic acid / 2-Arachidonoylglycerol / Amidase / Oxylipin |
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| Research Abstract |
Cannabinoids are bioactive components of marijuana. Receptors for the exogenous cannabinoids were earlier isolated, and their cDNAs were cloned. As an endogenous ligand for the cannabinoid receptors, arachidonoylethanolamide was isolated and referred to as anandamide. A better understanding of the physiological function of anandamide requires the studies on the biosynthesis and metabolism of anandamide. An international collaboration project was carried out by Japanese, Italian and American reearch groups, and the following experimental results were obtained.
1) A possible reversible hydrolysis and synthesis of anandamide was earlier demonstrated by Ueda et al.using a partially purified enzyme of porcine brain, and was now confirmed by the use of a recombinant enzyme prepared by overexpression of cDNA of a similar enzyme of rat liver.
2) Selective inhibitors of anandamide amidohydrolase were screened in collaboration of Japanese, American and Italian groups, and arachidonoyldiazomethylketone was found to be most inhibitory with IC_<50> values of 3-6 muM.
3) 2-Arachidonoylglycerol was recently shown to be another ligand to cannabinoid receptors. Japanese and Italian groups demonstrated that both anandamide and 2-arachidonoylglycerol were hydrolyzed by the same enzyme.Piomelli et al.suggested taht these ligands mediated lon-term potentiation.
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