Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosis
Jae Young Choi, … , John W. Hanrahan, Jeffrey J. Wine
Jae Young Choi, … , John W. Hanrahan, Jeffrey J. Wine
Published October 1, 2007
Citation Information: J Clin Invest. 2007;117(10):3118-3127. https://doi.org/10.1172/JCI31992.
View: Text | PDF
Research Article Pulmonology

Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosis

  • Text
  • PDF
Abstract

Cystic fibrosis (CF) is caused by dysfunction of the CF transmembrane conductance regulator (CFTR), an anion channel whose dysfunction leads to chronic bacterial and fungal airway infections via a pathophysiological cascade that is incompletely understood. Airway glands, which produce most airway mucus, do so in response to both acetylcholine (ACh) and vasoactive intestinal peptide (VIP). CF glands fail to secrete mucus in response to VIP, but do so in response to ACh. Because vagal cholinergic pathways still elicit strong gland mucus secretion in CF subjects, it is unclear whether VIP-stimulated, CFTR-dependent gland secretion participates in innate defense. It was recently hypothesized that airway intrinsic neurons, which express abundant VIP and ACh, are normally active and stimulate low-level gland mucus secretion that is a component of innate mucosal defenses. Here we show that low levels of VIP and ACh produced significant mucus secretion in human glands via strong synergistic interactions; synergy was lost in glands of CF patients. VIP/ACh synergy also existed in pig glands, where it was CFTR dependent, mediated by both Cl– and HCO3–, and clotrimazole sensitive. Loss of “housekeeping” gland mucus secretion in CF, in combination with demonstrated defects in surface epithelia, may play a role in the vulnerability of CF airways to bacterial infections.

Authors

Jae Young Choi, Nam Soo Joo, Mauri E. Krouse, Jin V. Wu, Robert C. Robbins, Juan P. Ianowski, John W. Hanrahan, Jeffrey J. Wine

×

Figure 1

Dose-response relations for airway gland mucus secretion.

Options: View larger image (or click on image) Download as PowerPoint
Dose-response relations for airway gland mucus secretion.
Shown are pig ...
Shown are pig (A and C) and human (B and D) responses to carbachol (Carb; A and B) and VIP (C and D). Each point is the result of measurements of 21–43 glands in 4 pigs or 3–4 humans. Vmax values were as follows (in nl/min/gland): carbachol-exposed pig, 3.43 ± 0.29; carbachol-exposed human, 3.55 ± 0.11; VIP-exposed pig, 1.58 ± 0.18; VIP-exposed human, 1.54 ± 0.09. EC50 values were as follows (in nM): carbachol-exposed pig, 590 ± 16; carbachol-exposed human, 545 ± 42; VIP-exposed pig, 834 ± 311; VIP-exposed human, 717 ± 76.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts