| Project/Area Number |
12680640
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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 |
Functional biochemistry
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| Research Institution | Teikyo University |
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Principal Investigator |
WAKU Keizo Faculty of Pharmaceutical Sciences ,. Teikyo University, Professor, 薬学部, 教授 (90013854)
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| 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)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| 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)
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| Keywords | 2-Arachidonoyglycerol / Cannabinoid receptor / CB2 / HL-60 cells / MAP kinase / Anandamide / Chemokine / Hypotension / 神経伝達 / 血管系 |
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| 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.
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