Role of IP and cADPR in Ca^<2+> -mediated signal transduction in airway cells.

1.环ADP核糖（cADPR）参与肺泡巨噬细胞ATP激活的K^+电流从大鼠气道灌洗获得的肺泡巨噬细胞（Mphi）对细胞外ATP产生瞬时外向K^+电流（I_K）。细胞内Ca^2+释放激活I_K。用IP_3或cADPR灌注细胞也可引起I_K。用IP_3灌流的细胞对细胞外ATP仍有反应，而用cADPR处理的细胞则无反应。胞浆内注射cADPR拮抗剂8-amino-cADPR可阻断ATP诱导的I_K。RT-PCR检测到Mphi细胞中存在ADP-核糖环化酶/cADPR水解酶CD 38的mRNA，并且Mphi细胞匀浆具有cADPR合成和水解的酶活性。这些发现表明cADPR在肺泡Mphi中作为细胞外ATP的Ca^<2+>释放第二信使起作用。囊性纤维化跨膜传导调节因子在SO_2致兔支气管炎中的表达探讨 ...更多信息 本实验以家兔吸入SO_2 ~ 7周作为支气管炎模型，观察了气道上皮细胞离子转运异常的情况。在正常气管中，顶端ATP诱导的短路电流（Isc）的短暂激活，随后抑制，而支气管炎模型表现出长期激活无抑制。这种病理性ATP反应可被DPC（一种Cl^-通道阻断剂）或无Cl^-溶液消除。异丙肾上腺素或腺苷可引起SO_2暴露气管Isc持续增加，而在正常气管则无此作用。北方杂交结果显示，SO2暴露组上皮细胞CFTR mRNA表达增强。免疫组化结果显示，CFTR仅在SO_2染毒兔的腔室细胞上呈阳性标记。我们的结论是，在支气管炎模型中延长的ATP反应是一个叠加的正常和腺苷激活电流。后者电流也被异丙肾上腺素激活，并出现作为支气管炎气道的签名电流。少

1. Involvement of cyclic ADP-ribose (cADPR) in ATP-activated K^+ -current in alveolar macrophages. Alveolar macrophages (Mphi) obtained from rat airway-lavage responded to extracellular ATP with a transient outward K^+ current (I_K). I_K was revealed to be activated by Ca^<2+> released intracellularly. Cellular perfusion with IP_3 or cADPR also elicited I_K. The cells perfused with IP_3 still responded to extracellular ATP,whereas those treated with cADPR did not. A cytoplasmic injection of 8-amino-cADPR (a cADPR antagonist) abolished the ATP-induced I_K. The mRNA of CD38, which is ADP-ribosyl cyclase/cADPR hydrolase, was detected in Mphi by RT-PCR.Moreover, Mphi homogenate showed enzymatic activities of cADPR synthesis and hydrolysis. These findings indicate that cADPR operates in alveolar Mphi as a Ca^<2+> -releasing second messenger for extracellular ATP.2. Upregulation of cystic fibrosis transmembrane conductance regulator (CFTR) in SO_2-induced bronchitis in rabbit. To investigate … More abnormalities of epithelial ion transport in inflammatory airways, rabbits exposed to SO_2 for-7 wks were used as a model of bronchitis. In normal trachea, apical ATP induced a transient activation of short circuit current (Isc) followed by a suppression, whereas the bronchitis model exhibited a prolonged activation without suppression. This pathological ATP response was abolished by DPC,a Cl^- channel blocker, or Cl^--free solution. Isoproterenol or adenosine evoked a sustained Isc increase in SO_2-exposed, but not in normal.tracheas. The Northern blot analysis showed a strong expression of CFTR-mRNA in SO2-exposed epithelium. The immunohistochemical study revealed a positive label of CFTR on cells located luminally only in SO_2-exposed rabbits. We concluded that the prolonged ATP-response in the bronchitis model was of a superimposed normal and adenosine-activated current. The latter current was also activated by isoproterenol and appeared as a signature current for the bronchitis airway. Less