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

IP和cADPR在气道细胞中Ca 2+ 介导的信号转导中的作用。

• 批准号: 07670650
• 负责人: SASAKI Tsukasa
• 金额: $ 1.54万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670650/
• 关键词: inositol trisphosphate; cyclic ADP-ribose; calcium; CFTR; alveolar macrophage; Chronic bronchitis; epithelial ion transport; signal transduction; 気道分泌腺; 気道平滑筋細胞; 気道上皮細胞; 塩素イオン分泌; 塩素イオンチャンネル

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

1. 环adp核糖（cADPR）参与肺泡巨噬细胞atp激活的K^+电流。通过大鼠气道灌洗获得的肺泡巨噬细胞（Mphi）对细胞外ATP具有瞬时外向K^+电流（I_K）。I_K被细胞内释放的Ca^<2+>激活。IP_3或cADPR灌注细胞也能诱导I_K。IP_3灌注的细胞仍对细胞外ATP有反应，而cADPR处理的细胞则无反应。胞质注射8-氨基-cADPR（一种cADPR拮抗剂）可消除atp诱导的I_K。RT-PCR检测Mphi中adp -核糖基环化酶/cADPR水解酶CD38 mRNA的表达。此外，Mphi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Ca^<2+> -释放细胞外atp的第二信使起作用。so_2诱导兔支气管炎囊性纤维化跨膜传导调节因子（CFTR）的上调。短句来源为了进一步研究炎性气道上皮离子转运的异常情况，采用SO_2暴露7周的家兔作为支气管炎模型。在正常气管中，顶端ATP诱导短路电流（Isc）的短暂激活，随后抑制，而支气管炎模型则表现出不受抑制的长时间激活。这种病理ATP反应被DPC（一种Cl^-通道阻滞剂）或无Cl^-溶液所消除。异丙肾上腺素或腺苷引起so_2暴露的Isc持续增加，但在正常气管中没有。Northern blot分析显示，在二氧化硫暴露的上皮中，CFTR-mRNA表达强烈。免疫组织化学研究显示，在so_2暴露的家兔中，CFTR在光定位的细胞上呈阳性标记。我们得出结论，支气管炎模型中延长的atp反应是正常和腺苷激活电流的叠加。后一种电流也被异丙肾上腺素激活，并作为支气管炎气道的特征电流出现。少

项目成果

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M.Nagaki、H.Ishihara 等人：“速激肽诱导猫气管粘膜下腺腺泡细胞中的 [Ca^2>]_i 升高。”

S.Ebihara, T.Sasaki, et al.: "Role of Cyclic ADP-ribose in ATP-activated potassium currents in alveolar macrophage." Journal of Biological Chemistry. (in press.). (1997)

S.Ebihara、T.Sasaki 等人：“环 ADP-核糖在肺泡巨噬细胞 ATP 激活钾电流中的作用”。

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S. Ebihara, T. Sasaki, et al.: "Role of Cyclic ADP-ribose in ATP-activated potassium currents in alveolar macrophage." Journal of Biological Chemistry. (in press). (1997)

S. Ebihara、T. Sasaki 等人：“环 ADP-核糖在肺泡巨噬细胞 ATP 激活钾电流中的作用”。

M. Satoh, M. Yamaya, et al.: "Isoproterenal augments ATP-evoked Cl^- secretion across canine tracheal epithelium." Respiration Physiology. 99. 13-18 (1995)

M. Satoh、M. Yamaya 等人：“异丙肾上腺素可增强犬气管上皮中 ATP 诱发的 Cl^- 分泌。”