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

药物诱导的胃肠道收缩似乎取决于胃肠道起搏细胞活动驱动的节律性收缩的程度。在长期给予中和性抗c-Kit单克隆抗体（ACK 2）的BALB/c小鼠中，胃肠道的节律性收缩受损，并且对药物的收缩反应，包括乙酰胆碱、前列腺素F_（2α）、缓激肽等。胃肠道中c-kit阳性细胞的组织化学分析显示，在ACK 2处理的动物中c-kit阳性细胞的数量减少，这导致节律性收缩受损。由于原代培养的肠c-kit阳性细胞产生了Ca^2+依赖性的节律性Cl^-电流，因此推测该节律性电流是胃肠起搏器的起源。药物引起的收缩异常的程度与节律性收缩受损的程度相关。The Bounces ...更多信息 当用25℃的低温器官浴溶液灌注对照动物的胃肠道节段时，模拟了ACK 2给药动物制剂中药物诱导的收缩（伴有节律性收缩受损）。这些结果表明，c-kit细胞节律性兴奋性输入所触发的平滑肌细胞节律性兴奋放电调节药物引起的收缩程度。α_1-酸性糖蛋白的舒张作用可能是通过阻断血管内皮细胞内Ca^<2+>进入VDCC或NSCC而不是激活NO通路。α_1-酸性糖蛋白引起的短暂舒张在外周血管中可能表现为长时间的舒张，从而改善炎症组织的血液循环。少

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