Satoh M, Shimura S, Ishihara H, Nagaki M, Sasaki H, Takishima T
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Respiration. 1992;59(3):145-50. doi: 10.1159/000196045.
Although much attention has been paid to the effect of endothelin on the bronchopulmonary system, there are few reports concerning the effect of endothelin on Cl- secretion across airway epithelium. We examined the effects of endothelin-1, -2 and -3 on bioelectric parameters of canine tracheal epithelium, a tissue in which Cl- is actively secreted and Na+ is absorbed. Potential difference (PD) and short-circuit current (SCC) were measured using an Ussing chamber with 0.5 cm2 of exposed area, and conductance (G) was calculated by dividing SCC by PD. Luminal endothelin-1 produced transient increases in PD and SCC, returning to baseline values within 5 min after stimulation in a dose-dependent fashion and reached mean responses of 123 and 126% of baseline PD and SCC, respectively, at 10(-6) M of endothelin-1, whereas submucosal endothelin-1 did not alter PD and SCC. G remained unchanged when stimulated by endothelin-1. Endothelin-2 and -3 did not produce any significant alterations in PD and SCC. Endothelin-1 evoked increases in PD and SCC, which were not altered by pretreatment with luminal amiloride (10(-4) M), or by treatment with submucosal propranolol (10(-5) M). Ionic substitution of Cl- with nontransported anions, iodide and gluconate, inhibited endothelin-1-induced increases in PD and SCC. Pretreatment with 10(-5) M indomethacin partially inhibited Endothelin-1-evoked increases in PD and SCC. These findings indicate that endothelin-1 stimulates Cl- secretion partially through the generation of cyclooxygenase products of arachidonic acid.
尽管内皮素对支气管肺系统的作用已受到广泛关注，但关于内皮素对气道上皮细胞氯分泌作用的报道却很少。我们研究了内皮素 -1、-2 和 -3 对犬气管上皮生物电参数的影响，该组织中氯被主动分泌而钠被吸收。使用暴露面积为 0.5 cm² 的尤斯灌流小室测量电位差（PD）和短路电流（SCC），并通过将 SCC 除以 PD 计算电导（G）。腔内给予内皮素 -1 可使 PD 和 SCC 短暂升高，刺激后 5 分钟内恢复至基线值，且呈剂量依赖性，在 10⁻⁶ M 内皮素 -1 时，平均反应分别达到基线 PD 和 SCC 的 123%和 126%，而黏膜下给予内皮素 -1 则不改变 PD 和 SCC。内皮素 -1 刺激时 G 保持不变。内皮素 -2 和 -3 对 PD 和 SCC 无显著影响。内皮素 -1 引起的 PD 和 SCC 升高不受腔内给予氨氯吡咪（10⁻⁴ M）预处理或黏膜下给予普萘洛尔（10⁻⁵ M）处理的影响。用非转运阴离子碘化物和葡萄糖酸盐替代氯离子可抑制内皮素 -1 诱导的 PD 和 SCC 升高。用 10⁻⁵ M 吲哚美辛预处理可部分抑制内皮素 -1 引起的 PD 和 SCC 升高。这些发现表明，内皮素 -1 部分通过花生四烯酸的环氧化酶产物生成来刺激氯分泌。
