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Am J Physiol Lung Cell Mol Physiol 283: L329-L335, 2002. First published April 12, 2002; doi:10.1152/ajplung.00277.2001
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Vol. 283, Issue 2, L329-L335, August 2002

Liquid secretion inhibitors reduce mucociliary transport in glandular airways

Stephen T. Ballard1, Laura Trout1, Anil Mehta2, and Sarah K. Inglis2

1 Department of Physiology, College of Medicine, University of South Alabama, Mobile, Alabama 36688; and 2 Department of Child Health, Ninewells Hospital, Dundee University, Dundee DD1 9SY, United Kingdom

Because of its possible importance in cystic fibrosis (CF) pulmonary pathogenesis, the effect of anion and liquid secretion inhibitors on airway mucociliary transport was examined. When excised porcine tracheas were treated with ACh to induce gland liquid secretion, the rate of mucociliary transport was increased nearly threefold from 2.5 ± 0.5 to 6.8 ± 0.8 mm/min. Pretreatment with both bumetanide and dimethylamiloride (DMA), to respectively inhibit Cl- and HCO<UP><SUB>3</SUB><SUP>−</SUP></UP> secretion, significantly reduced mucociliary transport in the presence of ACh by 92%. Pretreatment with the anion channel blocker 5-nitro-2-(3-phenylpropylamino)benzoic acid similarly reduced mucociliary transport in ACh-treated airways by 97%. These agents did not, however, reduce ciliary beat frequency. Luminal application of benzamil to block liquid absorption significantly attenuated the inhibitory effects of bumetanide and DMA on mucociliary transport. We conclude that anion and liquid secretion is essential for normal mucociliary transport in glandular airways. Because the CF transmembrane conductance regulator protein likely mediates Cl-, HCO<UP><SUB>3</SUB><SUP>−</SUP></UP>, and liquid secretion in normal glands, we speculate that impairment of gland liquid secretion significantly contributes to defective mucociliary transport in CF.

cystic fibrosis; submucosal glands; chloride secretion; ciliary beat frequency; bicarbonate secretion


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