Mechanism of substance P-induced liquid secretion across bronchial epithelium.
Mechanism of substance P-induced liquid secretion across bronchial epithelium.
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P 物质诱导支气管上皮液体分泌的机制。
DOI：
10.1152/ajplung.2001.281.3.l639
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Ballard,ST
中科院分区：
文献类型：
--
作者：
Trout,L;Corboz,MR;Ballard,ST
本研究旨在确定非胆碱能通路诱导液体分泌的机制。当暴露于乙酰胆碱、P物质或福斯克林时，切除的猪支气管分泌大量的液体，但不暴露于异丙肾上腺素、去甲肾上腺素或苯肾上腺素。布美他尼是一种Na+-K+-2Cl -共转运抑制剂，可使液体分泌对P物质的反应降低69%。大约三分之二的布美他尼不敏感的液体分泌被二甲胺（DMA）（一种Na+/H+交换抑制剂）阻断。去除表面上皮后，气道中P物质反应得以保留，提示分泌液体来源于粘膜下腺。阴离子通道阻滞剂二苯胺-2-羧酸酯（DPC）和5-硝基-2-（3-苯基丙胺）苯甲酸（NPPB）抑制bbb90 %的p物质诱导的液体分泌，而DIDS没有作用。DMA、DPC和NPPB对净hco分泌的抑制作用大于对液体分泌的抑制作用。虽然保存相对于液体分泌，净hco分泌减少39%存在布美他尼。我们得出结论，P物质通过主动运输Cl -和HCO诱导猪支气管粘膜下腺分泌液体。对分泌激动剂和拮抗剂的反应模式表明，囊性纤维化跨膜传导调节剂介导了这一过程。
The present study was undertaken to identify and determine the mechanism of noncholinergic pathways for the induction of liquid secretion across airway epithelium. Excised porcine bronchi secreted substantial and significant quantities of liquid when exposed to acetylcholine, substance P, or forskolin but not to isoproterenol, norepinephrine, or phenylephrine. Bumetanide, an inhibitor of Na+-K+-2Cl−cotransport, reduced the liquid secretion response to substance P by 69%. Approximately two-thirds of bumetanide-insensitive liquid secretion was blocked by dimethylamiloride (DMA), a Na+/H+exchange inhibitor. Substance P responses were preserved in airways after surface epithelium removal, suggesting that secreted liquid originated from submucosal glands. The anion channel blockers diphenylamine-2-carboxylate (DPC) and 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) inhibited >90% of substance P-induced liquid secretion, whereas DIDS had no effect. DMA, DPC, and NPPB had greater inhibitory effects on net HCOsecretion than on liquid secretion. Although preserved relative to liquid secretion, net HCOsecretion was reduced by 39% in the presence of bumetanide. We conclude that substance P induces liquid secretion from bronchial submucosal glands of pigs through active transport of Cl−and HCO. The pattern of responses to secretion agonists and antagonists suggests that the cystic fibrosis transmembrane conductance regulator mediates this process.