Acetylcholine-induced liquid secretion by bronchial epithelium: role of Cl- and HCO3- transport.
Inhibitors of Cl- and HCO-3 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 HCO-3 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 microM acetylcholine, the airways secreted 13.4 +/- 0.7 microliter. cm-2. h-1. Bumetanide (10 microM) pretreatment reduced acetylcholine-induced liquid and Cl- secretion rates by approximately 70%, but HCO-3 secretion fell by only 40%. Dimethylamiloride (DMA; 100 microM) pretreatment reduced Cl- secretion rates by approximately 15%, but HCO-3 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 HCO-3 secretion. We speculate that the principal source of this liquid is submucosal glands. Crossover inhibition of bumetanide on HCO-3 secretion and DMA on Cl- secretion implies modulation of anion secretion secondary to changes in cell electrolyte composition.
Trout
L
L
Department of Physiology, College of Medicine, University of South Alabama, Mobile, Alabama 36688, USA.
Gatzy
J T
JT
Ballard
S T
ST
D000109:Acetylcholine / Q000494:pharmacology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000037:antagonists & inhibitors / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D002034:Bumetanide / Q000494:pharmacology; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000378:metabolism; D004357:Drug Synergism; D004848:Epithelium / Q000378:metabolism; D013552:Swine
D001639:Bicarbonates; D002712:Chlorides; D002034:Bumetanide; C039465:5-dimethylamiloride; D000584:Amiloride; D000109:Acetylcholine