Effect of anion transport inhibition on mucus secretion by airway
submucosal glands.
Inglis, Sarah K., Michel R. Corboz, Aubrey E. Taylor, and Stephen T.
Ballard.
Department of Physiology, College of Medicine, University of South
Alabama, Mobile, AL 36688
APStracts 3:0231L, 1996.
To model the airway glandular defect in cystic fibrosis, the effect of
anion secretion blockers on submucosal gland mucus secretion was
investigated. Porcine distal bronchi were isolated, pretreated with a
Cl- secretion blocker (bumetanide) and/or a combination of blockers
to inhibit HCO3- secretion (dimethylamiloride (DMA), acetazolamide
and diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)), and then
treated with acetylcholine (ACh), a glandular liquid and mucus
secretagogue. Bronchi were then fixed, sectioned and stained for
mucins. Each gland duct was ranked for mucin content from 0 (no
mucin) to 5 (duct completely occluded with mucin). Untreated bronchi,
bronchi treated only with ACh, and ACh-treated bronchi that received
either bumetanide or the HCO3- secretion blockers all exhibited low
gland duct mucin content (1.18+/-0.34, 0.59+/-0.07, 0.65+/-0.03 and
0.83+/-0.11, respectively). However, pretreatment with both Cl- and
HCO3- secretion blockers before ACh addition resulted in substantial
and significant ductal mucus accumulation (3.57+/-0.22). In situ
videomicroscopy studies of intact airways confirmed these results.
Thus, inhibition of the anion (and presumably liquid) secretion
response to ACh leads to mucus obstruction of submucosal gland ducts
that resembles the early pathological changes observed in CF.
Received 13 August 1996; accepted in final form 15 November 1996.
APS Manuscript Number L259-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996