| Project/Area Number |
13306023
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | THE UNIVERSITY OF TOKYO |
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Principal Investigator |
HORI Masatoshi The University of Tokyo, Graduate School of Agriculture and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (70211547)
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| Co-Investigator(Kenkyū-buntansha) |
MOMOTANI Eiichi National Institute of Animal Health, Chief researcher, 室長(研究職) (50355145)
SATO Koichi Yamaguchi University, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (90205914)
OZAKI Hiroshi The University of Tokyo, Graduate School of Agriculture and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (30134505)
KARAKI Hideaki Azabu University, Department of Veterinary Medicine, Visiting Professor, 獣医学部, 客員教授
HIKONO Hirokazu National Institute of Animal Health, Researcher, 研究員 (60355146)
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| Project Period (FY) |
2001 – 2003
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| Keywords | macrophage / gut motility / inflammation / prostaglandins / smooth muscle / contraction / nitric oxide / IL-1β |
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| Research Abstract |
Intestinal motility is under the control of several systems, including the neurogenic, myogenic and endocrine systems. Morphological and functional studies in recent years have suggested that interstitial cells of Cajal (ICCs) are pacemakers in the musculature of the gastrointestinal tract. ICCs are arranged in distinctive patterns in close relation to nerve and smooth muscle cells in the muscle layer, and generate pacemaker currents to develop electrical slow waves in the gastrointestinal smooth muscles. In addition, muscularis resident macrophages are regularly distributed in the subserosa and at the level of the myenteric plexus. However, it remains to be determined how these cells coordinately contribute to the GI motility. In this study, we have obtained the following results :
1)Inhibition of spontaneous contractions and peristalsis in circular smooth muscle from the colons of Crohn's disease model (TNBS-treated) rats is attributable to the impairment of ICCs and myenteric nerve systems. The indication of macrophage activation and the close correlation between the degeneration and macrophage accumulation suggest that the macrophages play critical a role in the degenerative pathology of intestinal motility.
2)Decrease in the contraction of circular smooth muscle isolated from TNBS induced colitis rat colon is attributable to the decreased activity of the L type Ca-channel. The dysfunction of the L type Ca-channel may be mediated by NF-κB-dependent pathways.
3)Treatment, of smooth muscle with IL-1□, which is derived mainly from macrophages, decreases either CPI-17 expression or MYPT I phosphorylation, which results in an increase in myosin phosphatase activity to reduce force generation. IL-1□ could be an important mediator of gastrointestinal motility disorders in IBD, etc.
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