权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Roles of Kit signalling in smooth muscle tissues

Kit 信号传导在平滑肌组织中的作用

基本信息

批准号：
13470020
负责人：
NISHI Katsuhide
金额：
$ 7.04万
依托单位：
KUMAMOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470020/
关键词：
smooth muscle Kit autonomic motility pacemaker mouse Ca^<2+>patch-clamp technique 細胞内Ca^<2+>貯蔵部位 caffeine

项目摘要

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.

为了阐明受体型酪氨酸激酶 Kit 在平滑肌组织自主运动中的作用，我们研究了小鼠胃肠道中 Kit 阳性 (Kit^+) 细胞的功能和数量。通过使用出生后8天腹腔注射中和Kit抗体（ACK2）的BALB/c小鼠，发现Kit信号传导在“Cajal间质细胞（ICCs）”的分化和增殖中发挥着至关重要的作用，“Cajal间质细胞（ICCs）”作为胃肠道运动中的起搏器和神经调节介质。利用制霉菌素穿孔膜片钳技术，Kit^+-细胞产生有节律的Ca^<2+>-激活的Cl^-电流。在ACK2处理的小鼠中，胃肠道的节律性收缩受损，并且对药物(包括缓激肽、乙酰胆碱和前列腺素F_2a)的收缩反应异常增强。药物引起的异常收缩伴随着节律性收缩受损，通过25℃低温器官浴液灌注的效果来模拟。总而言之，Kit 信号传导在 ICC 起搏功能的发展中发挥着重要作用，并且平滑肌细胞的节律性兴奋放电（可能由 ICC 的节律性电输入触发）调节药物诱导的收缩程度。