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

• 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

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) 是一种多用途信使分子，由一氧化氮合酶 (NOS) 从氨基酸 L-精氨酸产生，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。在本研究中，我们研究了NO在体外调节气道上皮离子转运功能和体内跨上皮电位差（PD）中的作用。神经激肽A（NKA）和P物质（SP）的添加以浓度依赖性方式增加犬培养的气管上皮细胞的短路电流，并且这些作用被去苯胺羧酸盐消除，但阿米洛利不能消除。 NKA 和 SP 也增加了气管跨上皮 PD。细胞预孵育或气管灌注 NG-硝基-L-精氨酸甲酯 (L-NAME,1 mM) 减弱了 NKA 和 SP 诱导的短路电流增加，并且阿米洛利敏感的 PD，导致剂量反应曲线向右位移，而 NG-硝基-D-精氨酸（D-NAME，1 mM）则不会。 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 的释放是通过使用该分子的特定电流传感器实时测量灌注液中的 NO 浓度 ([NO]) 来确定的。 NKA 和 SP 以剂量依赖性方式增加 [NO]。因此，速激肽在体外增加短路电流，在体内增加阿米洛利敏感的PD，这可能反映了气管粘膜中Cl从粘膜下层向呼吸管腔的移动，并且上皮细胞产生NO可能参与了这一过程。