| Project/Area Number |
15591922
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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 |
Emergency medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
NINOMIYA Norifiumi Nippon Medical School, Medical faculty, Assistant Professor, 医学部, 助教授 (70180677)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Naoshige Nippon Medical School, Medical faculty, Assistant Professor, 医学部, 助手
YAMAMOTO Yasuhiro Nippon Medical School, Medical faculty, Professor, 大学院・医学研究科, 教授 (70125079)
SUZUKI Hidenori Nippon Medical School, Medical faculty, Professor, 大学院・医学研究科, 教授 (30221328)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | endotoxin / guinea pig / ileus / cannabinoid / anandamide / 2-arachidonoylglycerol / lipopolysaccharide / intestine |
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| Research Abstract |
We investigated the participation of endogenous cannabinoids in the mechanism of paralitic ileus in the endotoxin- induced ileus model of guinea pigs.
Intestinal muscle tension in conscious, unrestrained guinea pigs was observed by telemetry through a force transducer sutured to the taenia caecum. Following intraperitonial administration of endotoxin (lipopolysaccharide, LPS) and cannabinoids(anandamide, AEA and 2-arachidonoylglycerol,2-AG), the muscle tension of the taenia caecum decreased dose-dependently. Decreases in muscle tension were suppressed by pre-treatment with AM281,a cannabinoid CB1 receptor antagonist, but not with AM630,a CB2 receptor antagonist.
Following LPS administration, endocannabinoid levels in guinea pig plasma were measured using LC/MS/MS analysis. Among post-LPS endocannabinoid levels,2-AG levels increased significantly 1 hour after LPS administration, while AEA levels were below detection limits.
The fact that LPS-induced paralytic ileus is suppressed following administration of a CB1 receptor antagonist, suggests that a signaling pathway associated with CB1 receptor plays a role in the biological actions of LPS. Increases in blood 2-AG levels one hour after LPS administration suggest regulation of physiological responses by the endocannabinoid system during endotoxicosis.
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