Tamaoki J, Sakai N, Isono K, Kanemura T, Chiyotani A, Yamauchi F, Takizawa T, Konno K
First Department of Medicine, Tokyo Women's Medical College, Japan.
Int Arch Allergy Appl Immunol. 1991;95(2-3):169-73. doi: 10.1159/000235424.
We studied the effect of substance P (SP) on the electric properties of cultured canine tracheal epithelium and its possible modulation by neutral endopeptidase (NEP) by Ussing's short-circuited technique in vitro. Addition of SP (5 x 10(-6) M) to the mucosal side increased short-circuit current (SCC) from 5.1 +/- 0.9 to 10.3 +/- 2.2 microA/cm2 (mean +/- SE; p less than 0.01), which was accompanied by increases in transepithelial potential difference and conductance. The effect of the mucosal SP on SCC was dose-dependent, with the maximal increase from the baseline value being 5.8 +/- 1.0 microA/cm2 observed at 5 x 10(-5) M. The NEP inhibitor phosphoramidon (10(-5) M) did not affect these responses. On the other hand, SCC was not altered by the addition of SP to the submucosal side. However, it was increased dose-dependently in the presence of phosphoramidon (10(-5) M) but not in the presence of captopril, bestatin or leupeptin. This stimulatory effect of submucosal SP was abolished by furosemide, diphenylamine-2-carboxylate and Cl-free medium, but not by amiloride. These results suggest that SP may selectively stimulate Cl secretion across the airway epithelium and that this effect may be modulated by submucosal NEP.
我们采用体外Ussing短路技术研究了P物质（SP）对培养的犬气管上皮细胞电特性的影响及其可能受到中性内肽酶（NEP）的调节作用。在黏膜侧添加SP（5×10⁻⁶ M）可使短路电流（SCC）从5.1±0.9微安/平方厘米增加至10.3±2.2微安/平方厘米（均值±标准误；p＜0.01），同时跨上皮电位差和电导也增加。黏膜侧SP对SCC的影响呈剂量依赖性，在5×10⁻⁵ M时观察到相对于基线值的最大增加量为5.8±1.0微安/平方厘米。NEP抑制剂磷酰胺素（10⁻⁵ M）不影响这些反应。另一方面，向黏膜下层添加SP不会改变SCC。然而，在存在磷酰胺素（10⁻⁵ M）时SCC呈剂量依赖性增加，而在存在卡托普利、贝抑素或亮抑酶肽时则不会增加。黏膜下层SP的这种刺激作用可被呋塞米、二苯胺-2-羧酸盐和无氯培养基消除，但不受氨氯吡咪影响。这些结果表明，SP可能选择性地刺激气道上皮细胞的氯离子分泌，且这种作用可能受到黏膜下层NEP的调节。
