Roles of c-kit in development and pathophysiology of smooth muscle

c-kit 在平滑肌发育和病理生理学中的作用

• 批准号: 13670091
• 负责人: TOKUTOMI Yoshiko
• 金额: $ 2.3万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670091/
• 关键词: smooth muscle; c-kit; mouse; contraction; intracellular Ca^<2+>; pacemaker; α_1-acid glycoprotein; パッチクランプ法; 等尺性張力; ryanodine感受性Ca^<2+>放出; caffeine; ryanodine; 細胞内Ca^<2+>貯蔵部位

Drug-induced contraction of gastrointestinal tracts seems to depend upon the extent of their rhythmic contraction that is driven by the activity of gastrointestinal pacemaker cells. In BALB/c mice chronically administered with a neutralizing anti-c-Kit monoclonal antibody (ACK2), rhythmic contraction of gastrointestinal tract was impaired and contractile responses to drugs., including acetylcholine, prostaglandin F_<2α> and bradykinin were anomalously augmented. Histochemical analysis of the c-kit positive cells in the gastrointestinal tract revealed the decreased number of c-kit positive cells in the ACK2-treated animals, which lead to the impaired rhythmic contraction. Since the intestinal c-kit positive cells in primary culture developed Ca^<2+>-dependent rhythmic Cl^-current, the rhythmic current is supposed to be an origin of gastrointestinal pacemakers. The extent of anomaly in drug-induced contraction correlated with the extent of impairment in rhythmic contraction. The anomalou … More s drug-induced contraction in the preparation from ACK2-treated animals, which is accompanied by the impaired rhythmic contraction, was mimicked when the gastrointestinal segments from control animals were superfused with a low temperature organ bath solution at 25℃. These results suggest that rhythmic discharge of excitation of smooth muscle cells, which is triggered by rhythmic excitatory input from c-kit cells, regulates the extent of drug-induced contraction.We have demonstrated that human α_1-acid glycoprotein produces a transient relaxation in the mouse aorta precontracted with phenylephrine. It is more likely that the α_1-acid glycoprotein-induced relaxation is due to block of Ca^<2+>-entry through VDCC or NSCC in the smooth muscle cells rather than activation of endothelial NO pathway. The transient relaxation induced by α_1-acid glycoprotein might occur as prolonged relaxation in the peripheral blood vessel, which may result in improvement of the blood circulation at tissue with inflammation. Less

项目成果

松元 一明, 他: "α_1-酸性糖蛋白質の血液循環系に及ぼす作用"人工血液. 11・2. 144-150 (2003)

松本和明等：“α_1-酸性糖蛋白对血液循环系统的影响”人工血液11・2。

Okuda, S., et al.: "Noradrenaline receptor-mediated potentiation of caffeine-induced Ca^<2+>-activated K^+ currents in bovine ciliary muscle cells"Current Eye Research. (in press). (2002)

Okuda，S.等人：“牛睫状肌细胞中咖啡因诱导的Ca 2+ 激活的K 2 电流的去甲肾上腺素受体介导的增强”当前眼科研究。

Tokutomi, Y., et al.: "消化管自律運動の遺伝子基盤と病態"日本薬理学雑誌. 119・4. 227-234 (2002)

Tokutomi, Y.等人：“胃肠道自主运动的遗传基础和病理学”日本药理学杂志119・4（2002）。

Okuda T., et al.: "Noradrenaline receptor-mediated potentiation of caffeine-induced Ca^<2+>-activated K^+ currents in bovine ciliary muscle cells."Curr.Eye Res.. 23. 455-462 (2002)

Okuda T.等人：“牛睫状肌细胞中咖啡因诱导的Ca 2+ 激活的K 2 电流的去甲肾上腺素受体介导的增强。”Curr.Eye Res.. 23. 455-462 (2002)

Tokutomi Y., et al.: "Genetic basis of autonomic gastrointestinal motility and pathophysiological models."Folia Pharmacol.Jpn.. 119. 227-234 (2002)

Tokutomi Y.等人：“自主胃肠运动和病理生理学模型的遗传基础”。Folia Pharmacol.Jpn.. 119. 227-234 (2002)