Mucociliary clearance and submucosal gland secretion in the ex vivo ferret trachea

Author:

Jeong Jin Hyeok12,Joo Nam Soo1,Hwang Peter H.3,Wine Jeffrey J.1

Affiliation:

1. Cystic Fibrosis Research Laboratory, Stanford University, Stanford, California;

2. Department of Otolaryngology-Head and Neck Surgery, Hanyang University School of Medicine, Seoul, Korea; and

3. Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California

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 Ca2+ 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.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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