CFTR involvement in chloride, bicarbonate, and liquid secretion by airway submucosal glands.
Previous studies demonstrated that ACh-induced liquid secretion by porcine bronchi is driven by active Cl(-) and HCO(-)(3) secretion. The present study was undertaken to determine whether this process was localized to submucosal glands and mediated by the cystic fibrosis transmembrane conductance regulator (CFTR). When excised, cannulated, and treated with ACh, porcine bronchi secreted 15.6 +/- 0.6 microliter. cm(-2). h(-1). Removal of the surface epithelium did not significantly affect the rate of secretion, indicating that the source of the liquid was the submucosal glands. Pretreatment with diphenylamine-2-carboxylate, a relatively nonselective Cl(-)-channel blocker, significantly reduced liquid secretion by 86%, whereas pretreatment with DIDS, which inhibits a variety of Cl(-) channels but not CFTR, had no effect. When bronchi were pretreated with glibenclamide or 5-nitro-2-(3-phenylpropylamino)benzoic acid (both inhibitors of CFTR), the rate of ACh-induced liquid secretion was significantly reduced by 39 and 91%, respectively, compared with controls. Agents that blocked liquid secretion also caused disproportionate reductions in HCO(-)(3) secretion. Polyclonal antibodies to the CFTR bound preferentially to submucosal gland ducts and the surface epithelium, suggesting that this channel was localized to these sites. These data suggest that ACh-induced gland liquid secretion by porcine bronchi is driven by active secretion of both Cl(-) and HCO(-)(3) and is mediated by the CFTR.
Ballard
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ST
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688, Alabama. sballard@usamail.usouthal.edu
Trout
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Bebök
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Sorscher
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Crews
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001826:Body Fluids / Q000187:drug effects / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism*; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D002712:Chlorides / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009092:Mucous Membrane / Q000378:metabolism; D013552:Swine; D014018:Tissue Distribution
D001639:Bicarbonates; D018118:Chloride Channels; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000109:Acetylcholine