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Role of nitric oxide in the regulation of airway iontransport

一氧化氮在气道离子输送调节中的作用

基本信息

批准号：
08670681
负责人：
TAMAOKI Jun
金额：
$ 1.54万
依托单位：
Tokyo Women's Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670681/
关键词：
Airwat epithelium Ion transport Nitric oxide Cyclic AMP Cyclic GMP Cl channel Airway inflammation Asthma サイクリック AMP Cl チャネルサイクリック GMP Cl分泌 β刺激薬タキキニン

项目摘要

There is increasing evidence that nitric oxide (NO), a multipurpose messenger molecule generated from the amino acid L-arginine by nitric oxide synthase (NOS), plays a role in a variety of airway functions including vascular and airway smooth muscle tone, host defense, and pulmonary neurotransmission. In the present study, we investigated the role of NO in the regulation of airway epithelial ion tmsport function in vitro and transepithelial potential difference (PD) in vivo. Additoin of neurokinin A (NKA) and substance P (SP) increased short-circuit current of canine cultured tracheal epithelial cells in a concentratino-dependent manner, and these effects were abolished by dephenylamine carboxylate but not by amiloride. Tracheal transepithelial PD was also increased by NKA and SP.Preincubation of cells or tracheal perfusion with NG-nitro-L-arginine methylester (L-NAME,1 mM) attenuated the NKA- and SP-induced increase in short-circuit current and the amiloride-sensitive PD,causing a rightward displacement of the dose-response curves, whereas NG-nitro-D-arginine (D-NAME,1 mM) did not. The inhibitory effect of L-NAME was reversed by L-arginine (10 mM) but not by D-arginine (10 mM). The release of NO was determined by a real-time measurement of NO concentration ([NO]) in the perfusate using specific amperometric sensors for this molecule. NKA and SP increased [NO] in a dose-dependent manner. Therefore, tachykinins increase short-circuit current in vitro and amiloride-sensitive PD in vivo, which probably reflect Cl movement from the submucosa toward the respiratory lumen in tracheal mucosa and that NO generation by epithelial cells may be involved in this process.

越来越多的证据表明，一氧化氮（NO），一氧化氮合酶（NOS）从氨基酸L-精氨酸产生的多用途信使分子，在多种气道功能中发挥作用，包括血管和气道平滑肌张力，宿主防御和肺神经传递。本研究探讨了NO在体外气道上皮细胞离子转运功能和体内跨上皮电位差（PD）调节中的作用。神经激肽A（NKA）和P物质（SP）可浓度依赖性地增加培养的犬气管上皮细胞的短路电流，这种作用可被去苯胺羧酸盐阻断，但不能被阿米洛利阻断。NKA和SP也增加了气管跨上皮PD。细胞预孵育或气管灌流NG-硝基-L-精氨酸甲酯（L-NAME，1 mM）衰减NKA和SP诱导的短路电流和阿米洛利敏感的PD增加，导致剂量-反应曲线的急剧位移，而NG-硝基-D-精氨酸（D-NAME，1 mM）没有。L-NAME的抑制作用可被L-精氨酸（10 mM）逆转，但不能被D-精氨酸（10 mM）逆转。NO的释放通过使用针对该分子的特定电流传感器实时测量灌注液中的NO浓度（[NO]）来确定。NKA和SP呈剂量依赖性增加[NO]。因此，速激肽增加短路电流在体外和阿米洛利敏感的PD在体内，这可能反映氯运动从粘膜下层向呼吸腔在气管粘膜和NO的产生上皮细胞可能参与了这一过程。