Ionic mechanism of forskolin-induced liquid secretion by porcine bronchi.
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 (Jv) of porcine distal bronchi. The forskolin-induced Jv was driven by a combination of bumetanide-sensitive Cl- secretion and DIDS-sensitive HCO3- secretion. When Cl- secretion was inhibited with bumetanide, Na+/H+ exchange-dependent HCO3- secretion was apparently induced to compensate for the loss of Cl- secretion. The forskolin-induced Jv 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 Jv 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+ -HCO3- cotransporter or an Na+-dependent anion exchanger, which could account for transepithelial HCO3- secretion.
Ballard
Stephen T
ST
Department of Physiology, College of Medicne, University of South Alabama, Mobile, AL 36688, USA. sballard@usouthal.edu
Trout
Laura
L
Garrison
Jennifer
J
Inglis
Sarah K
SK
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism; D001639:Bicarbonates / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism*; D002034:Bumetanide / Q000008:administration & dosage / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology*; D004357:Drug Synergism; D007322:Instillation, Drug; D007473:Ion Channels / Q000037:antagonists & inhibitors; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine
D000838:Anions; D001639:Bicarbonates; D002712:Chlorides; D007473:Ion Channels; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide; D005576:Colforsin; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid