Takemura H, Tamaoki J, Tagaya E, Chiyotani A, Konno K
First Department of Medicine, Tokyo Women's Medical College, Japan.
J Pharmacol Exp Ther. 1995 Jul;274(1):584-8.
To determine whether nitric oxide (NO) formation is involved in Cl secretion across airway mucosa in response to beta adrenergic agonists, we studied the effect of isoproterenol (ISO) on the Cl diffusion potential difference of rabbit tracheal mucosa and measured NO formation by a highly specific electrode for this molecule in vivo. Perfusion of ISO on the tracheal mucosal surface increased the Cl diffusion potential difference, as determined in the presence of amiloride, in a dose-dependent fashion, the maximal increase from the base-line value being 12.1 +/- 1.7 mV (P < .001). Application of NG-nitro-L-arginine methylester (10(-3) M) decreased the Cl diffusion potential difference by itself and attenuated the subsequent response to ISO, causing a rightward displacement of ISO concentration-response curves, whereas NG-nitro-D-arginine methylester had no effect. This inhibitory effect of NG-nitro-L-arginine methyl-ester was reversed by L-arginine but not by D-arginine. Addition of ISO dose-dependently increased polarographic current and, hence, NO concentration in the perfusate, the maximal increase from the base-line levels being 178 +/- 10 nM. Histochemistry for NADPH diaphorase activity showed a strong staining within epithelial cells. These results suggest that NO formation may play a role in the beta adrenoceptor-mediated Cl secretion by tracheal mucosa.
为了确定一氧化氮（NO）的生成是否参与β肾上腺素能激动剂刺激下气道黏膜的氯离子分泌，我们研究了异丙肾上腺素（ISO）对兔气管黏膜氯离子扩散电位差的影响，并在体内用一种针对该分子的高特异性电极测量了NO的生成。在存在氨氯吡咪的情况下，在气管黏膜表面灌注ISO会以剂量依赖的方式增加氯离子扩散电位差，相对于基线值的最大增加幅度为12.1±1.7 mV（P<.001）。应用NG-硝基-L-精氨酸甲酯（10⁻³ M）本身会降低氯离子扩散电位差，并减弱随后对ISO的反应，导致ISO浓度-反应曲线向右移位，而NG-硝基-D-精氨酸甲酯则没有影响。NG-硝基-L-精氨酸甲酯的这种抑制作用可被L-精氨酸逆转，但不能被D-精氨酸逆转。添加ISO会剂量依赖性地增加极谱电流，从而增加灌流液中的NO浓度，相对于基线水平的最大增加幅度为178±10 nM。NADPH黄递酶活性的组织化学显示上皮细胞内有强烈染色。这些结果表明，NO的生成可能在β肾上腺素能受体介导的气管黏膜氯离子分泌中起作用。
