| Project/Area Number |
10470025
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | KUMAMOTO UNIVERSITY |
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Principal Investigator |
NISHI Katsuhide Kumamoto University, School of Medicine, Associate professor, 医学部, 教授 (00040220)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUTOMI Yoshiko Kumamoto University, School of Medicine, Assistant Professor, 医学部, 助手 (90253723)
TOKUTOMI Naofumi Kumamoto University, School of Medicine, Associate professor, 医学部, 助教授 (30227582)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2000: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Keywords | c-kit / development / smooth muscle / mouse / pacemaker / Ca^<2+> storage / intracellular Ca^<2+> / c-kit陽性細胞 / リアノジン受容体 / イノシトール三燐酸受容体 / Ca^<2+>放出機構 / マウス膀胱平滑筋 / 細胞内Ca濃度 / カフェイン・カルバコール応答 / TEA感受性Ca^<2+>活性化K^+電流 |
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| Research Abstract |
c-kit, a receptor-type tyrosine kinase may regulate development of smooth muscle tissue in the mammalian gastrointestinal tract. To illustrate how c-kit plays roles in the functional development of the smooth muscle tissue, we surveyed change in the population and function of c-kit-positive (c-kit^+) cells, i.e. interstitial cells of Cajal, in the developing gastrointestinal tract of BALB/c mice intraperitoneally injected with the neutralizing anti-c-kit-monoclonal antibody (ACK2) for 8 days after birth. In control animals, the c-kit^+ cells constructed networks, contacting with both enteric nervous system and smooth muscle layers, but not in the ACK2-treated animals that had impaired spontaneous contractility of the intestine because of lack of the c-kit^+ cells. that possessed rhythmic Ca^<2+>-activated Cl^-conductance. It is also found that the c-kit^+ cells in the pacemaker region of the small intestine arid the longitudinal smooth muscle cells developed from the same kit-positive precursor cells, depending upon the extent of kit signals.
In smooth muscle cells dissociated from gastrointestinal tract of the ACK2-treated animals, dysfunction in the ryanodine-sensitive Ca^<2+> storage in the cytoplasm was suggested when tested with caffeine-induced Ca^<2+>-activated K^+ currents under voltage-clamp conditions and fura-2 fluorometric measurements of intracellular Ca^<2+> concentration. Altogether, it is suggested that c-kit plays important roles in regulating development of the function of mammalian gastrointestinal tract.
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