2003 Fiscal Year Final Research Report Summary
Physiological roles of 2-arachidonoylglycerol in the nervous system and the immune system
| Project/Area Number |
14580653
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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 Teikyo University, Faculty of Pharmaceutical Science, Professor, 薬学部, 教授 (90013854)
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| Co-Investigator(Kenkyū-buntansha) |
KISHIMOTO Seishi Teikyo University, Faculty of Pharmaceutical Science, Associate Professor, 薬学部, 助手 (60234217)
YAMASHITA Atsushi Teikyo University, Faculty of Pharmaceutical Science, Associate Professor, 薬学部, 助教授 (80230415)
SUGIURA Takayuki Teikyo University, Faculty of Pharmaceutical Science, Professor, 薬学部, 教授 (40130009)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Cannabinoid / 2-Arachidonoylglycerol / Anandamide / CB1 Receptor / CB2 Receptor / Glutamic acid / Chemokine / Chemotaxis |
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| Research Abstract |
1. The generation of 2-AG in the brain was first examined. In this study, we examined the synthesis of 2-AG in rat brain slices, We found that the level of 2-AG was augmented markedly in depolarized rat brain slices. The generation of 2-AG was also observed in glutamate-stimulated brain slices. We also found that treatment of synaptosomes with SR141716A significantly enhanced the release of glutamate from synaptosomes upon depolarization. These results strongly suggest that 2-AG released from stimulated neurons may have an important physiological role in the attenuation of synaptic transmission by acting on the CB1 receptor expressed. primarily in the presynapse
2. Physiological roles of 2-AG in inflammation was next examined. We found that 2-AG induces the migration of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes. The 2-AG-induced migration of HL-60 cells was markedly reduced when the cells were pretreated with either SR 144528 or PTX, suggesting that the migration was mediated through the CB2 receptor and Gi/Go. The 2-AG-induced migration was also observed with KHYG-1 human natural killer cells and human peripheral blood natural killer cells. We also found that the addition of 2-AG to HL-60 cells enhanced the production of chemokines such as IL-8 and MCP-1 through a CB2 receptor-and Gi/Go-dependent mechanism. Finally, we examined the generation of 2-AG at the site of inflammation. We found that the level of 2-AG was markedly elevated in mouse peritoneal cavity injected with carrageenan. These results strongly suggest that 2-AG has a stimulative rather than suppressive role during inflammatory reactions and immune 1 responses
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