Involvement of inflammatory cells on the dysmotility of gastrointestinal smooth muscles in experimental colitis model animals.
| Project/Area Number |
15580260
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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 |
Basic veterinary science/Basic zootechnical science
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| Research Institution | Yamaguchi University |
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Principal Investigator |
SATO Koichi Yamaguchi University, Department of Agriculture, Associate Professor, 農学部, 助教授 (90205914)
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| Co-Investigator(Kenkyū-buntansha) |
NASU Tetsuyuki Yamaguchi University, Department of Agriculture, Professor, 農学部, 教授 (70035559)
HAYASHI Toshiharu Yamaguchi University, Department of Agriculture, Professor, 農学部, 教授 (90111484)
MORIMOTO Masahiro Yamaguchi University, Department of Agriculture, Assistant Professor, 農学部, 助手 (30274187)
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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 |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Inflammatory Bowel Disease / IL-1β / gastrointestinal motility / CPI-17 / macrophage / プロテアーゼ受容体2 / 1L-1β / サイトカイン / 収縮 / ミオシンリン酸化 / ミオシンフォスファターゼ |
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| Research Abstract |
The mechanism of gastro-intestinal dysmotility in the inflammatory bowel disease has not been cleared. In this study, we examined the mechanism involved in the inflamed distal colon isolated from dextran sodium sulphate-induced ulcerative colitis model mouse (DSS-treated mouse). Although substance P-induced contraction was not changed, carbachol-induced contraction was reduced in DSS-treated mouse colon. Pre-incubation with NO synthase inhibitor, L-NMMA, cyclooxygenase inhibitor, indomethacin, or ATP-sensitive K^+ channel inhibitor, glibenclamide, did not recovered the carbachol-induced contraction in DSS-treated moue colon. In semi-quantitative RT-PCR experiments and Western blotting analysis, muscarinic M_3 receptor expressions were not changed. The Ca^<2+>-sensitization of contractile elements induced by carbachol with GTP or GTP_YS was reduced in the β-escin permeabilized DSS-treated mouse colon. Although the expression of proteins, such as rhoA, ROCK1 or ROCK2, that are involved i
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n G-protein coupled signaling in smooth muscles, were not changed, the expression of CPI-17, the functional proteins involved in the smooth muscle Ca^<2+>-sensitization, was significantly decreased in DSS-treated mouse colon. These results suggest that the suppression of carbachol-induced contraction in colitis mouse is attributable at lease partially to the increased activity of myosin phosphatase following the down regulation of CPI-17.
Protease activated receptor-2 (PAR-2) is highly expressed in gastrointestinal tract and is activated by proteases released form mast cell and trypsin in intestinal lumen. PAR-2-acitivation induces a relaxation of colonic smooth muscle which is important for the motility. In order to elucidate the relationship of dysmotility of colon in ulcerative colitis model rat and PAR-2, we used the dextran sodium sulphate-induced ulcerative colitis model rat (DSS rat). In the control rat colon, trypsin induced relaxation of carbachol (CCh) and high KCl-induced contraction, which is completely resolved by the pretreatment of apamin. In DSS rat colon, these inhibitory effects of trypsin on CCh and high KCl-induced contraction were significantly reduced. In DSS rat colon, the relaxation induced by SLIGRL-NH was also reduced, but the inhibitory effect of EBIO-1, SK_<Ca> activator, has not been changed. In RT-PCR experiments, the expression of PAR-2 mRNA of colonic smooth muscle decreased in DSS rat from control rat. These results suggest that suppression of PAR-2 activator-induced relaxation in colitis rat colon is attributable to the down regulation of PAR-2 mRNA expression level. It is shown that gastro-intestinal-dysmotility is at least partially due to the down regulation of PAR-2 in IBD. Less
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Report
(3 results)
Research Products
(1 results)
