| Project/Area Number |
13470020
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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, 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) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | smooth muscle / Kit / autonomic motility / pacemaker / mouse / Ca^<2+> / patch-clamp technique / 細胞内Ca^<2+>貯蔵部位 / caffeine |
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| Research Abstract |
To clarify the roles of Kit, a receptor-type tyrosine kinase, in autonomic motility of smooth muscle tissues, we investigated the function and population of Kit-positive (Kit^+) cells in the gastrointestinal tracts of mice. By using of BALB/c mice intraperitoneally injected with neutralizing Kit antibody (ACK2) for 8 days after birth, it was found that Kit signalling plays crucial roles in the differentiation and proliferation of 'interstitial cells of Cajal (ICCs)' as pacemakers and mediators of neural regulation in gastrointestinal motility.
Under voltage-clamped conditions with the nystatin-perforated patch-clamp technique, Kit^+-cells developed rhythmic Ca^<2+>-activated Cl^- currents. In the ACK2-treated mice, rhythmic contraction of the gastrointestinal tracts was impaired and the contractile responses to drugs, including bradykinin, acetylcholine and prostaglandin F_<2a>, were anomalously augmented. The anomalous drug-induced contraction, which was accompanied by the impaired rhythmic contraction, was mimicked by the effect of superfusion with a low temperature organ bath solution at 25 ℃. Altogether, it is suggested that Kit signalling plays important roles in development of pacemaking function of ICCs and that rhythmic discharge of excitation of the smooth muscle cells, which may be triggered by rhythmic electrical input from ICCs, regulates the extent of drug-induced contraction.
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