| Project/Area Number |
02454138
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 Medical School Professor, 医学部, 教授 (00040220)
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| Co-Investigator(Kenkyū-buntansha) |
TOKUTOMI Naohumi Kumamoto University Asistant Medical School Professor, 医学部, 講師 (30227582)
荒木 春夫 熊本大学, 医学部, 助教授 (80151158)
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| Project Period (FY) |
1990 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1992: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | cardiac action potential / ionic channel in excitable membrane / inplannted myocardium / gut pacemaker mechanism / protooncogene c-kit / protein tyrosinekinase / intestinal smooth muscle / developmental process of intestinal movement / 腸管平滑節細胞 / 腸管ペースメーカー活動 / プロトオンコジーンc-kit / カハール細胞 / 抗c-kit発現チロシンキナーゼ抗体 / 腸管運動の発達 / アセチルコリン / プロスタグランジンF_2α / イオンチャネル / マウス胎児心筋 / Cーkitプロトオンコジ-ン / リセプタ-・チロシンキナ-ゼ / 腸管ペ-スメ-カ-機構 / 心筋ペ-スメ-カ- / カハ-ル細胞 / 発達過程 / Naチャネル / Kチャネル |
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| Research Abstract |
Developmental changes in contractile responses of the isolated ileum of BALB/c mice treated with an antagonistic anti c-kit monoclonal antibody (ACK2) to bradykinin (BK) and acetylcholine (ACh) were examined in vitro. Isolated ileum longitudinal muscle of new-born mice (BALB/c) started to show regular rhythmic contraction 4 days after birth, but pre-treatment with ACK2 for 4 days postnatally resulted in failure of postnatal development of the regular activity of the intestine. ACH(10^<-8>M>) induced sustained contraction in a dose-dependent manner in both ACK2 treated and control ileum obtained from mice of the same age group. The sensitivity to ACh was augmented in the ACK2-treated group. The response to ACh was blocked by atropine (10^<-7>M). BK(8x10^<-11>M) produced marked contraction followed by relaxation in the ACK2-treated ileum, while in the control ileum the agent (8x10^<-9>M) induced only a small transient increase in the amplitude of spontaneous contraction. Tetrodotoxin (10^<-7>M) did not alter the response to BK in both ACK2 treated and control groups. Voltage-clamp analyses of the Ca^<2+>-dependent ionic currents in dissociated smooth muscle cells from mice treated with or without ACK2 also revealed developmental differences in both ACh and BK responses. These findings suggest that c-kit expressing cells play a crucial role in development of intracellular mechanisms for Ca^<2+> handing for contraction and relaxation in intestinal smooth muscle or in membrane sensitivity to BK and other substances.
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