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Am J Physiol Lung Cell Mol Physiol 284: L855-L862, 2003. First published January 10, 2003; doi:10.1152/ajplung.00348.2002
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Vol. 284, Issue 5, L855-L862, May 2003

Secretion of acid and base equivalents by intact distal airways

S. K. Inglis, S. M. Wilson, and R. E. Olver

Tayside Institute of Child Health, University of Dundee, Dundee DD1 9SY, United Kingdom

Secretion of HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> by airway submucosal glands is essential for normal liquid and mucus secretion. Because the liquid bathing the airway surface (ASL) is acidic, it has been proposed that the surface epithelium may acidify HCO<UP><SUB>3</SUB><SUP>−</SUP></UP>-rich glandular fluid. The aim of this study was to investigate the mechanisms by which intact distal bronchi, which contain both surface and glandular epithelium, modify pH of luminal fluid. Distal bronchi were isolated from pig lungs, cannulated in a bath containing HCO<UP><SUB>3</SUB><SUP>−</SUP></UP>-buffered solution, and perfused continually with an aliquot of similar, lightly buffered solution (LBS) in which NaCl replaced NaHCO<UP><SUB>3</SUB><SUP>−</SUP></UP> (pH 7 with NaOH). The pH of this circulating LBS initially acidified (by 0.053 ± 0.0053 pH units) and transepithelial potential difference (PD) depolarized. The magnitude of acidification was increased when pHLBS was higher. This acidification was unaffected by luminal dimethylamiloride (DMA, 100 µM) but was inhibited by 100 nM bafilomycin A1 (by 76 ± 13%), suggesting involvement of vacuolar-H+ ATPase. Addition of ACh (10 µM) evoked alkalinization of luminal LBS and hyperpolarization of transepithelial PD. The alkalinization was inhibited in HCO<UP><SUB>3</SUB><SUP>−</SUP></UP>-free solutions containing acetazolamide (1 mM) and by DMA and was enhanced by bumetanide (100 µM), an inhibitor of Cl- secretion. The hyperpolarization was unaffected by these maneuvers. The anion channel blocker 5-nitro-2-(3-phenylpropylamino)benzoate (300 µM) and combined treatment with DMA and bumetanide blocked both the alkalinization and hyperpolarization responses to ACh. These results are consistent with earlier studies showing that ACh evokes glandular secretion of HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> and Cl-. Isolated distal airways thus secrete both acid and base equivalents.

airway epithelium; bicarbonate transport; pH


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