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

Abstract

Inhibitors of Cl− and[Formula: see text] 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[Formula: see text] 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 μM acetylcholine, the airways secreted 13.4 ± 0.7 μl ⋅ cm−2 ⋅ h−1. Bumetanide (10 μM) pretreatment reduced acetylcholine-induced liquid and Cl− secretion rates by ∼70%, but [Formula: see text] secretion fell by only 40%. Dimethylamiloride (DMA; 100 μM) pretreatment reduced Cl− secretion rates by ∼15%, but[Formula: see text] 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[Formula: see text] secretion. We speculate that the principal source of this liquid is submucosal glands. Crossover inhibition of bumetanide on [Formula: see text]secretion and DMA on Cl−secretion implies modulation of anion secretion secondary to changes in cell electrolyte composition.

Gel-forming mucins form distinct morphologic structures in airways

“…S1 A and B). These studies are consistent with earlier work (21,23,24) and suggest that loss of anion secretion in submucosal glands alters the properties of mucus.…”

“…Finding more mucus-filled ducts in CF is in seeming contrast with previous studies showing that CF submucosal glands are smaller and secrete less liquid than non-CF (28,30,31). However, less liquid secretion together with more mucus filling of the ducts suggests that the mucus has abnormal biophysical properties, a conclusion consistent with earlier studies (21 (21,23,24). These studies were performed with excised airways submerged in saline.…”

“…MCT (21,23,24). These functional observations suggest that mucus forms discontinuous structures rather than a homogeneous layer on the airway surface.…”

“…In CF pigs, a decreased pH, rather than a decreased HCO 3 − concentration, increased airway surface liquid viscosity (29). Earlier studies in CF pigs showed that inhibiting both Cl − and HCO 3 − secretion in non-CF airways was required to produce mucus abnormalities that resemble those in CF (21,23,24). These observations suggest that both liquid volume and the pH or HCO 3 − concentration are important.…”

Inhaled isotonic alkaline versus saline solution and radioaerosol clearance in chronic cough

“…In Ems salt, compared to isotonic saline, the ionic composition is altered, Cl -being partially replaced by HCO 3 -, but the overall strength being unchanged. However, reducing the Clconcentration in the extemal medium may stimulate transepithelial Cl -transport in compensation, given the fact that the epithelium is less permeable to HCO 3 -than to Cl - [21], thereby promoting hydration of the airway surface fluid and improving its clearability.…”