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.

为了阐明试剂盒的作用，KIT的作用，接收器型酪氨酸激酶在平滑肌组织的自主运动中，我们研究了小鼠胃肠道中Kit阳性（Kit^+）细胞的功能和种群。通过使用腹膜内注射中和基因抗体（ACK2）的BALB/c小鼠出生后的8天，发现Kit信号在Cajal（ICC）的间质细胞的分化和增殖中起着至关重要的作用。 NYSTATIT蛋白的贴片钳技术，Kit^+ - 细胞发展了节奏的Ca^<2+> - 激活的Cl^ - 电流。在经过ACK2治疗的小鼠中，胃肠道的节奏收缩受损，并且对药物的收缩反应（包括颤音蛋白，乙酰胆碱和前列腺素F_ <2A>）被异常增强。异常的药物诱导的收缩是由节奏收缩受损进行的，它通过25°的低温器官浴溶液的超级灌注的效果模仿了。总而言之，建议套件信号在ICC的起搏功能的发展中起着重要作用，以及对平滑肌细胞兴奋的节奏排放，这可能是由ICC的节奏电输入触发的，从而调节了药物诱导的收缩程度。