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Several physiological functions of 2-arachido.noylglycerol; an endogenous cannabinoid receptor ligand

Research Project

Project/Area Number 12680640
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionTeikyo University

Principal Investigator

WAKU Keizo  Faculty of Pharmaceutical Sciences ,. Teikyo University, Professor, 薬学部, 教授 (90013854)

Co-Investigator(Kenkyū-buntansha) KISHIMOTO Seishi  Faculty of Pharmaceutical Sciences ,. Teikyo University, Research Associate, 薬学部, 助手 (60234217)
YAMASHITA Atsushi  Faculty of Pharmaceutical Sciences ,. Teikyo University, Associate Professor, 薬学部, 助教授 (80230415)
SUGIURA Takayuki  Faculty of Pharmaceutical Sciences ,. Teikyo University, Professor, 薬学部, 教授 (40130009)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywords2-Arachidonoyglycerol / Cannabinoid receptor / CB2 / HL-60 cells / MAP kinase / Anandamide / Chemokine / Hypotension / 神経伝達 / 血管系
Research Abstract

An endogenous cannabimimetic molecule, 2-arachidonoylglycerol, induces a rapid, transient increase in intracellular free Ca^<2+> concentrations in HL-60 cells through a cannabinoid CB2 receptor-dependent mechanism. We examined the activities of a number of relevant compounds (2-arachidonoylglycerol, its structural analogues, and several synthetic cannabinoids). We found that 2-arachidonoylglycerol is the most potent compound examined so far. These results strongly suggested that the cannabinoid CB2 receptor is originally a 2-arachidonoylglycerol receptor, and 2-arachidonoylglycerol is the intrinsic physiological ligand for the cannabinoid CB2 receptor which is known to be expressed mainly in the immune system. We also found that 2-arachidonoylglycerol induces the activation of p42/p44 MAP kinases and the enhanced production of kemokines such as IL-8 and MCP-1 in HL-60 cells. These results strongly suggest that 2-arachidonoylglycerol is an important mediator in the immune system, Next, we examined the level of 2-arachidonoylglycerol in the brain isolated from rats injected with picrotoxinin. We found that the level of 2-arachidonoylglycerol was augmented markedly in picrotoxinin-injected rat brain. Similar results were observed with decapitated rat brain. These results suggest that a substantial amount of 2-arachidonoylglycerol was produced in the brain under the condition of stimulation. We confirmed that a large amount of 2-arachidonoylglycerrol was generated rapidly in rat brain homogenate when incubated in the presence of C^<a2+>, We next examined the effect of 2-arachidonoylglycerol on the vascular system. We found that 2-arachidonoylglycerrol induces hypotension in rats. We also found that 2-arachidonoylglycerol enhanced norepinephrine release in isolated rat heart. These results suggest that 2-arachidonoylglycerol is a possible vasomodulator.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Kobayashi Y.: "Activation by 2-Arachidonoylglycerol, an Endogenous Cannabinoid Receptor Ligand, of p42/44 Mitogen-Activted Protein Kinase in HL-60 Cells"J.Biochem. 129. 665-669 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurihara J.: "2-Arachidonoylglyceorl and Anandamide Oppositely Modulate Norepinephrine Release from the Rat Heart Sympathetic Nerves"Jpn.J.Pharmacol. 87. 93-96 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kagota S.: "2-Arachidonoylglycerol, a candidate of endothelium-derived hyperpolarizing factor"Eur.J.Pharmacol. 415. 233-238 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiura T.: "2-Arachidonoylglycerol and the cannabinoid receptors"Chem.Phys.Lipids. 108. 89-106 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiura T.: "Evidence that 2-arachidonoylglycerol but not N-palmitoylethanolamine or anandamide is the pharmacological ligand for the cannabinoid CB2 receptor.Comparison of the agonistic activiteis of various cannabinoid receptor ligands in HL-60 cells"J.Biol.Chem.. 275. 605-612 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiura T.: "Generation of 2-arachidonoylglycerol an endogenous cannabinoid receptor ligand, in picrotoxinin-administered rat brain"Biochem.Biophys.Res.Commun. 275. 654-658 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 山下 純: "基礎生化学実験法 第5巻「脂質・糖質・複合脂質」"東京化学同人. 338 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kobayashi Y.: "Activation by 2-Arachidonoylglycerol, an Endogenous Cannabinoid Receptor Ligand, of p42/44 Mitogen-Activted Protein Kinase in HL-60 Cells"J. Biochem.. 129. 665-669 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurihara J.: "J-Arachidonoylglyceorl and Anandamide Oppositely Modulate Norepinephrine Release from the Rat Heart Sympathetic Nerves"Jpn. J. Pharmacol.. 87. 93-96 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kagota S.: "2-Arachidonoylglycerol, a candidate of endothelium-derived hyperpolarizing factor"Eur. J. Pharmacol.. 415. 233-238 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiura T.: "2-Arachidonoylglycerol and the cannabinoid receptors"Chem. Phys. Lipids. 108. 89-106 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiura T.: "Evidence that 2-arachidonoylglycerol but not N-palmitpylethanolamine or anandamide is the pharmacological ligand for the cannabinoid CB2 receptor. Comparison of the agonistic activities of various cannabinoid receptor ligands in HL-60 cells"J. Biol. Chem.. 275. 605-612 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiura T.: "Generation of 2-arachidonoylglycerol an endogenous cannabinoid receptor ligand, in picrotoxinin-administered rat brain"Biochem. Biophys. Res. Commun.. 275. 654-658 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamashita A.: "Thin layer chromatography"Kisosekagakujikkennhou 5 : Lipids・Sugar・Conjugated glycolipid, Tokyokagakudo-jin. 5-14 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiura T.: "2-Arachidonoylglycerol: an endogenous cannabinoid receptor agonist"World Rev.Nutr.Diet.. 88. 200-206 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kobayashi Y.: "Activation by 2-Arachidonoylglycerol,an Endogenous Cannabinoid Receptor Ligand,of P42/44 Mitogen-Activated Protein Kinase in HL-60 Cells"J.Biochem.. 129. 665-669 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamaguchi T.: "Endogenous cannabinoid,2-archidonoylglycerol,attenuates naloxone-precipitated withdrawal signs in morphine-dependent mice"Brain Res.. 909. 121-126 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kurihara J.: "2-Arachidonoylglycerol and Anandamide Oppositely Modulate Norepinephrine Release from the Rat Heart Sympathetic Nerves"Jpn.J.Pharmacol.. 87. 93-96 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suhara Y.: "Synthesis and Biological Activities of Novel Structural Analogues of 2-Arachidonoylglycerol,An Endogenous Cannabinoid Ligand"Bioorg.Med.Chem.Lett.. 11. 1985-1988 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kagota S.: "2-Arachidonoylglycerol,a candidate of endothelium-derived hyperpolirizing factor"Eur.J.Pharmacol.. 415. 233-238 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 山下 純: "基礎生化学実験法第5巻「脂質・糖質・複合脂質」"東京化学同人. 338 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugiura,T.: "Rapid generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in rat brain after decapitation"Neuroscience Lett.. 297. 175-178 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sugiura,T.: "Evidence that 2-arachidonoylglycerol but not N-plamitoylethanolamine or anandamide is the physiological ligand for the cannabinoid CB2 receptor"J.Biol.Chem.. 275・1. 605-612 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakane,S.: "Occurrence of a novel cannabimimetic molecule 2-sciadonoyglycerol (2-eicosa-5',11',14'-trienoylglycerol) in the umbrella pine"Bio.Pharm.Bull.. 23・6. 758-761 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sugiura,T.: "Generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in picrotoxin-administered rat brain"Biochem.Biophys.Res.Commun.. 271・3. 654-658 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Suhara,Y.: "Synthesis and biological activities of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, and its metabolically stable ether-linked analogs"Chem.and Pharmaceutical Bull.. 48・7. 903-907 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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