title: Mucociliary clearance and submucosal gland secretion in the ex vivo ferret trachea.
abstract: In many species submucosal glands are an important source of tracheal mucus, but the extent to which mucociliary clearance (MCC) depends on gland secretion is unknown. To explore this relationship, we measured basal and agonist-stimulated MCC velocities in ex vivo tracheas from adult ferrets and compared the velocities with previously measured rates of ferret glandular mucus secretion (Cho HJ, Joo NS, Wine JJ. Am J Physiol Lung Cell Mol Physiol 299: L124-L136, 2010). Stimulated MCC velocities (mm/min, means ± SE for 10- to 35-min period poststimulation) were as follows: 1 μM carbachol: 19.1 ± 3.3 > 10 μM phenylephrine: 15.3 ± 2.4 ≈ 10 μM isoproterenol: 15.0 ± 1.9 ≈ 10 μM forskolin: 14.6 ± 3.1 > 1 μM vasoactive intestinal peptide (VIP): 10.2 ± 2.2 >> basal (t15): 1.8 ± 0.3; n = 5-10 for each condition. Synergistic stimulation of MCC was observed between low concentrations of carbachol (100 nM) and isoproterenol (300 nM). Bumetanide inhibited carbachol-stimulated MCC by ~70% and abolished the increase in MCC stimulated by forskolin + VIP, whereas HCO3 (-)-free solutions did not significantly inhibit MCC to either intracellular Ca(2+) concentration or intracellular cAMP concentration ([cAMP]i)-elevating agonists. Stimulation and inhibition of MCC and gland secretion differed in several respects: most importantly, elevating [cAMP]i increased MCC much more effectively than expected from its effects on gland secretion, and bumetanide almost completely inhibited [cAMP]i-stimulated MCC while it had a smaller effect on gland secretion. We conclude that changes in glandular fluid secretion are complexly related to MCC and discuss possible reasons for this.
authors.affiliation: Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California; Department of Otolaryngology-Head and Neck Surgery, Hanyang University School of Medicine, Seoul, Korea; and.
authors.forename: Jin Hyeok
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California;
authors.forename: Nam Soo
authors.initials: NS
authors.lastname: Joo
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hwang
authors.affiliation: Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California; wine@stanford.edu.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Wine
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002254:Carbonates / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D003550:Cystic Fibrosis / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000235:genetics; D005088:Exocrine Glands / Q000378:metabolism*; D005260:Female; D005289:Ferrets; D017136:Ion Transport / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D009079:Mucociliary Clearance / Q000187:drug effects*; D009093:Mucus / Q000187:drug effects / Q000378:metabolism*; D009579:Nitrobenzoates / Q000494:pharmacology; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism*
chemical_list: D018712:Analgesics, Non-Narcotic; D020533:Angiogenesis Inhibitors; D001993:Bronchodilator Agents; D002254:Carbonates; D002712:Chlorides; D009579:Nitrobenzoates; D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D002217:Carbachol; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium
keywords: cystic fibrosis; ferret; mucociliary transport; submucosal gland