Mechanism of substance P-induced liquid secretion across bronchial epithelium

The present study was undertaken to identify and determine the mechanism of noncholinergic pathways for the induction of liquid secretion across airwa y epithelium. Excised porcine bronchi secreted substantial and significant quantities of liquid when exposed to acetylcholine, substance P, or forskol in but not to isoproterenol, norepinephrine, or phenylephrine. Bumetanide, an inhibitor of Na+-K+-2Cl- cotransport, reduced the liquid secretion respo nse to substance P by 69%. Approximately two-thirds of bumetanide-insensiti ve liquid secretion was blocked by dimethylamiloride (DMA), a Na+/H+ exchan ge inhibitor. Substance P responses were preserved in airways after surface epithelium removal, suggesting that secreted liquid originated from submuc osal glands. The anion channel blockers diphenylamine-2-carboxylate (DPC) a nd 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) inhibited >90% of sub stance P-induced liquid secretion, whereas DIDS had no effect. DMA, DPC, an d NPPB had greater inhibitory effects on net HCO3- secretion than on liquid secretion. Although preserved relative to liquid secretion, net HCO3- secr etion was reduced by 39% in the presence of bumetanide. We conclude that su bstance P induces liquid secretion from bronchial submucosal glands of pigs through active transport of Cl- and HCO3-. The pattern of responses to sec retion agonists and antagonists suggests that the cystic fibrosis transmemb rane conductance regulator mediates this process.