Molecular mechanism of development of mammalian smooth mscle

受体型酪氨酸激酶C-kit可能调节哺乳动物胃肠道平滑肌组织的发育。为了阐明c-kit在平滑肌组织功能发育中的作用，我们在BALB/c小鼠出生后8天内腹腔注射了中和性抗c-kit单克隆抗体（ACK2），研究了发育中的胃肠道中c-kit阳性（c-kit^+）细胞（即Cajal间质细胞）数量和功能的变化。在对照动物中，c-kit^+细胞构建了网络，与肠神经系统和平滑肌层接触，但在ack2处理的动物中没有，因为缺乏c-kit^+细胞而导致肠道自发收缩性受损。具有节律性Ca^<2+>-激活的Cl^-电导。研究还发现，小肠起搏器区的c-kit^+细胞和纵向平滑肌细胞由相同的kit阳性前体细胞发育而来，这取决于kit信号的程度。在与胃肠道分离的ack2处理动物的平滑肌细胞中，在电压箝位条件下用咖啡因诱导的Ca^<2+>激活的K^+电流和fura-2荧光法测量细胞内Ca^<2+>浓度时，发现细胞质中ryanodine敏感的Ca^<2+>储存功能障碍。综上所述，c-kit在哺乳动物胃肠道功能发育中起着重要的调节作用。

c-kit, a receptor-type tyrosine kinase may regulate development of smooth muscle tissue in the mammalian gastrointestinal tract. To illustrate how c-kit plays roles in the functional development of the smooth muscle tissue, we surveyed change in the population and function of c-kit-positive (c-kit^+) cells, i.e. interstitial cells of Cajal, in the developing gastrointestinal tract of BALB/c mice intraperitoneally injected with the neutralizing anti-c-kit-monoclonal antibody (ACK2) for 8 days after birth. In control animals, the c-kit^+ cells constructed networks, contacting with both enteric nervous system and smooth muscle layers, but not in the ACK2-treated animals that had impaired spontaneous contractility of the intestine because of lack of the c-kit^+ cells. that possessed rhythmic Ca^<2+>-activated Cl^-conductance. It is also found that the c-kit^+ cells in the pacemaker region of the small intestine arid the longitudinal smooth muscle cells developed from the same kit-positive precursor cells, depending upon the extent of kit signals.In smooth muscle cells dissociated from gastrointestinal tract of the ACK2-treated animals, dysfunction in the ryanodine-sensitive Ca^<2+> storage in the cytoplasm was suggested when tested with caffeine-induced Ca^<2+>-activated K^+ currents under voltage-clamp conditions and fura-2 fluorometric measurements of intracellular Ca^<2+> concentration. Altogether, it is suggested that c-kit plays important roles in regulating development of the function of mammalian gastrointestinal tract.