Roles of Kit signalling in smooth muscle tissues

为了阐明受体酪氨酸激酶Kit在平滑肌组织自主神经运动中的作用，我们研究了Kit阳性细胞在小鼠胃肠道中的功能和数量。通过给BALB/c小鼠注射中和试剂盒抗体(ACK2)8天后发现，Kit信号在胃肠道运动中作为起搏器和神经调节介质的Cajal间质细胞(ICCs)的分化和增殖中起关键作用。在制霉菌素穿孔膜片钳技术电压钳条件下，Kit^细胞产生节律性钙电流。在ACK2处理的小鼠中，胃肠道的节律性收缩受损，对药物的收缩反应异常增强，包括缓激肽、乙酰胆碱和前列腺素F_&lt；2a&gt；。用25℃低温器官浴液灌流模拟药物引起的异常收缩，并伴有节律性收缩受损。综上所述，Kit信号在ICCs起搏功能的发展中起着重要作用，ICCs节律性电输入可能触发的平滑肌细胞节律性兴奋放电调节药物引起的收缩幅度。

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.