Physiological roles of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand
| Project/Area Number |
16590063
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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 |
Biological pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
SUGIURA Takayuki Teikyo University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (40130009)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Atsushi Teikyo University, Faculty of Pharmaceutical Sciences, Associate professor, 薬学部, 助教授 (80230415)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Cannabinoid / 2-Arachidonoylglycerol / Inflammation / Immunity / CB2 receptor / Nitric oxide / Adhesion / CB2受容体 / アナンダミド / 好酸球 / NO |
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| Research Abstract |
In this study, we first investigated possible pathophysiological roles of the CB2 receptor and 2-AG in acute inflammation in mouse ear induced by the topical application of TPA. We found that the amount of 2-AG was markedly augmented in inflamed mouse ear. Importantly, TPA-induced ear swelling was blocked by treatment with SR144528, a CB2 receptor antagonist, suggesting that the CB2 receptor is involved in the swelling. The application of SR144528 also reduced the TPA-induced production of LTB_4 and the infiltration of neutrophils in the mouse ear. Similar results observed with oxazolone-induced allergic inflammation in mouse ear. Interestingly, the application of 2-AG to the mouse ear evoked swelling, which was abolished by treatment with SR144528. Nitric oxide was suggested to be involved in the ear swelling induced by 2-AG. These results suggest that the CB2 receptor and 2-AG play crucial stimulative roles during the course of inflammatory reactions.
We next examined the effect of 2-AG on the adhesion of HL-60 cells differentiated into macrophage-like cells. We found that 2-AG enhanced the adhesion of differentiated HL-60 cells to fibronectin and VCAM-1. The CB2 receptor, Gi/Go and PI 3-kinase were shown to be involved in 2-AG-induced augmented cell adhesion. 2-AG also enhanced the adhesion of human monocytic leukemia U937 cells and peripheral blood monocytes. These results strongly suggest that 2-AG plays some essential role in inflammatory reactions and immune responses by inducing robust adhesion to extracellular matrix proteins and adhesion molecules in several types of inflammatory cells and immune-competent cells.
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Report
(3 results)
Research Products
(12 results)
