Acetylcholine-induced liquid secretion by bronchial epithelium: role of Cl⁻ and HCO 3 − transport

Inhibitors of Cl- and HCO-3 secretion reduce acetylcholine-induced liquid, but not mucin, secretion by bronchial submucosal glands [S. K. Inglis, M. R. Corboz, A. E. Taylor, and S. T. Ballard. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L372-L377, 1997]. The present study quantified contributions of Cl- and HCO-3 transport to volume and composition of acetylcholine-induced liquid secretion by airway epithelium. When distal bronchi were excised from 33 pigs and treated with 10 microM acetylcholine, the airways secreted 13.4 +/- 0.7 microliter. cm-2. h-1. Bumetanide (10 microM) pretreatment reduced acetylcholine-induced liquid and Cl- secretion rates by approximately 70%, but HCO-3 secretion fell by only 40%. Dimethylamiloride (DMA; 100 microM) pretreatment reduced Cl- secretion rates by approximately 15%, but HCO-3 secretion fell 47%. DMA alone had little effect on liquid secretion. When airways were pretreated with both bumetanide and DMA, acetylcholine-induced liquid secretion was nearly abolished. We conclude that about three-fourths of acetylcholine-induced liquid secretion in distal bronchi is dependent on Cl- secretion. Most of the remaining response is driven by HCO-3 secretion. We speculate that the principal source of this liquid is submucosal glands. Crossover inhibition of bumetanide on HCO-3 secretion and DMA on Cl- secretion implies modulation of anion secretion secondary to changes in cell electrolyte composition.