EFFECT OF ANION SECRETION INHIBITORS ON MUCIN CONTENT OF AIRWAY SUBMUCOSAL GLAND DUCTS

In porcine bronchi, inhibition of both Cl- and HCO3- transport is requ ired to block the anion secretion response to ACh and to cause mucus a ccumulation within ACh-treated submucosal gland ducts [S. K. Inglis, M . R. Corboz, A. E. Taylor, and S. T. Ballard. Am. J. Physiol. 272 (Lun g Cell. Mol. Physiol. 16): L372-L377, 1997]. In this previous study, a combination of three potential HCO3- transport inhibitors [1 mM aceta zolamide, 1 mM DIDS, and 0.1 mM dimethylamiloride (DMA)] was used to b lock carbonic anhydrase, Cl-/HCO3- exchange, and Na+/H+ exchange, resp ectively. The aim of the present study was to obtain a better understa nding of the mechanism of ACh-induced HCO3- secretion in airway glands by determining which of the three inhibitors, in combination with bum etanide, is required to block anion secretion and so cause ductal muci n accumulation. Gland duct mucin content was measured in distal bronch i isolated from domestic pigs. Addition of either bumetanide alone, bu metanide plus acetazolamide, or bumetanide plus DIDS had no significan t effect on ACh-induced mean gland duct mucin content. In contrast, gl ands treated with bumetanide plus DMA as well as glands treated with a ll four anion transport blockers were almost completely occluded with mucin after the addition of ACh. These data suggest that mucin is clea red from the ducts of bronchial submucosal glands by liquid generated from Cl- and DMA-sensitive HCO3- transport.