M.J. Turner
Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator-dependent anion and fluid secretion in airway epithelia
Turner, M.J.; Saint-Crib, V.; Patel, W.; Ibrahim, S.H.; Verdon, B.; Ward, C.; Garnett, J.P.; Tarran, R.; Cann, M.J.; Gray, M.A.
Authors
V. Saint-Crib
W. Patel
S.H. Ibrahim
B. Verdon
C. Ward
J.P. Garnett
R. Tarran
Professor Martin Cann m.j.cann@durham.ac.uk
Professor
M.A. Gray
Abstract
Hypercapnia is clinically defined as an arterial blood partial pressure of CO2 of above 40 mmHg and is a feature of chronic lung disease. In previous studies we have demonstrated that hypercapnia modulates agonist-stimulated cAMP levels through effects on transmembrane adenylyl cyclase activity. In the airways, cAMP is known to regulate cystic fibrosis transmembrane conductance regulator (CFTR)-mediated anion and fluid secretion, which contributes to airway surface liquid homeostasis. The aim of the current work was to investigate if hypercapnia could modulate cAMP-regulated ion and fluid transport in human airway epithelial cells. We found that acute exposure to hypercapnia significantly reduced forskolin-stimulated elevations in intracellular cAMP as well as both adenosine and forskolin-stimulated increases in CFTR-dependent transepithelial short-circuit current, in polarised cultures of Calu-3 human airway cells. This CO2-induced reduction in anion secretion was not due to a decrease in HCO3− transport given that neither a change in CFTR-dependent HCO3− efflux, nor Na+/HCO3− cotransporter-dependent HCO3− influx were CO2-sensitive. Hypercapnia also reduced the volume of forskolin-stimulated fluid secretion over 24 h, yet had no effect on the HCO3− content of the secreted fluid. Our data reveal that hypercapnia reduces CFTR-dependent, electrogenic Cl− and fluid secretion, but not CFTR-dependent HCO3− secretion, which highlights a differential sensitivity of Cl− and HCO3− transporters to raised CO2 in Calu-3 cells. Hypercapnia also reduced forskolin-stimulated CFTR-dependent anion secretion in primary human airway epithelia. Based on current models of airways biology, a reduction in fluid secretion, associated with hypercapnia, would be predicted to have important consequences for airways hydration and the innate defence mechanisms of the lungs.
Citation
Turner, M., Saint-Crib, V., Patel, W., Ibrahim, S., Verdon, B., Ward, C., …Gray, M. (2016). Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator-dependent anion and fluid secretion in airway epithelia. The Journal of Physiology, 594(6), 1643-1661. https://doi.org/10.1113/jp271309
Journal Article Type | Article |
---|---|
Acceptance Date | Nov 5, 2015 |
Online Publication Date | Dec 20, 2015 |
Publication Date | Mar 15, 2016 |
Deposit Date | Nov 23, 2015 |
Publicly Available Date | Dec 20, 2016 |
Journal | Journal of Physiology |
Print ISSN | 0022-3751 |
Electronic ISSN | 1469-7793 |
Publisher | Wiley |
Peer Reviewed | Peer Reviewed |
Volume | 594 |
Issue | 6 |
Pages | 1643-1661 |
DOI | https://doi.org/10.1113/jp271309 |
Files
Accepted Journal Article
(964 Kb)
PDF
Copyright Statement
© 2015 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Published Journal Article
(987 Kb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
You might also like
Near atmospheric carbon dioxide activates plant ubiquitin cross-linking
(2023)
Journal Article
Allophycocyanin A is a carbon dioxide receptor in the cyanobacterial phycobilisome
(2022)
Journal Article
Carbon Dioxide and the Carbamate Post-Translational Modification
(2022)
Journal Article
Ubiquitin is a carbon dioxide-binding protein
(2021)
Journal Article
Downloadable Citations
About Durham Research Online (DRO)
Administrator e-mail: dro.admin@durham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search