Ionic mechanism of forskolin-induced liquid secretion by porcine bronchi

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 290; no. 1; pp. L97 - L104
• Main Authors: Ballard, Stephen T, Trout, Laura, Garrison, Jennifer, Inglis, Sarah K
• Format: Journal Article
• Language: English
• Published: United States 01.01.2006
• Subjects: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology; Animals; Anions - metabolism; Bicarbonates - antagonists & inhibitors; Bicarbonates - metabolism; Bronchi - drug effects; Bronchi - secretion; Bumetanide - administration & dosage; Bumetanide - pharmacology; Chlorides - metabolism; Colforsin - pharmacology; Drug Synergism; Instillation, Drug; Ion Channels - antagonists & inhibitors; Sodium Potassium Chloride Symporter Inhibitors - administration & dosage; Sodium Potassium Chloride Symporter Inhibitors - pharmacology; Swine
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.00159.2005

1 Department of Physiology, College of Medicine, University of South Alabama, Mobile, Alabama; and 2 Maternal and Child Health Sciences, Ninewells Hospital, Dundee University, Dundee, United Kingdom Submitted 11 April 2005 ; accepted in final form 4 August 2005 cAMP-elevating agents such as forskolin and vasoactive intestinal peptide induce liquid secretion by tracheobronchial submucosal glands. This pathway is thought to be CFTR dependent and thus defective in cystic fibrosis; however, the ionic mechanism that drives this secretion process is incompletely understood. To better define this mechanism, we studied the effects of ion transport inhibitors on the forskolin-induced liquid secretion response (J v ) of porcine distal bronchi. The forskolin-induced J v was driven by a combination of bumetanide-sensitive Cl – secretion and DIDS-sensitive HCO 3 – secretion. When Cl – secretion was inhibited with bumetanide, Na + /H + exchange-dependent HCO 3 – secretion was apparently induced to compensate for the loss of Cl – secretion. The forskolin-induced J v was significantly inhibited by the anion channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid, diphenylamine-2-carboxylate, and glibenclamide. We conclude that the forskolin-induced J v shares many characteristics of cholinergically induced secretion except for the presence of a DIDS-sensitive component. Although the identity of the DIDS-sensitive component is unclear, we speculate that it represents a basolateral membrane Na + -HCO 3 – cotransporter or an Na + -dependent anion exchanger, which could account for transepithelial HCO 3 – secretion. cystic fibrosis; airway liquid secretion; submucosal glands Address for reprint requests and other correspondence: S. T. Ballard, Dept. of Physiology, MSB 3074, Univ. of South Alabama, Mobile, AL 36688 (e-mail: sballard{at}usouthal.edu )