cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine
Summary: A controversial hypothesis pertaining to cystic fibrosis (CF) lung disease is that the CF transmembrane conductance regulator (CFTR) channel fails to inhibit the epithelial Na+ channel (ENaC), yielding increased Na+ reabsorption and airway dehydration. We use a non-invasive self-referencing...
Main Authors: | , , , , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Elsevier
2021-10-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721012559 |
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author | Xiaojie Luan Yen Le Santosh Jagadeeshan Brendan Murray James L. Carmalt Tanya Duke Shannon Beazley Masako Fujiyama Kurtis Swekla Bridget Gray Monique Burmester Veronica A. Campanucci Alan Shipley Terry E. Machen Julian S. Tam Juan P. Ianowski |
author_facet | Xiaojie Luan Yen Le Santosh Jagadeeshan Brendan Murray James L. Carmalt Tanya Duke Shannon Beazley Masako Fujiyama Kurtis Swekla Bridget Gray Monique Burmester Veronica A. Campanucci Alan Shipley Terry E. Machen Julian S. Tam Juan P. Ianowski |
author_sort | Xiaojie Luan |
collection | DOAJ |
description | Summary: A controversial hypothesis pertaining to cystic fibrosis (CF) lung disease is that the CF transmembrane conductance regulator (CFTR) channel fails to inhibit the epithelial Na+ channel (ENaC), yielding increased Na+ reabsorption and airway dehydration. We use a non-invasive self-referencing Na+-selective microelectrode technique to measure Na+ transport across individual folds of distal airway surface epithelium preparations from CFTR−/− (CF) and wild-type (WT) swine. We show that, under unstimulated control conditions, WT and CF epithelia exhibit similar, low rates of Na+ transport that are unaffected by the ENaC blocker amiloride. However, in the presence of the cyclic AMP (cAMP)-elevating agents forskolin+IBMX (isobutylmethylxanthine), folds of WT tissues secrete large amounts of Na+, while CFTR−/− tissues absorb small, but potentially important, amounts of Na+. In cAMP-stimulated conditions, amiloride inhibits Na+ absorption in CFTR−/− tissues but does not affect secretion in WT tissues. Our results are consistent with the hypothesis that ENaC-mediated Na+ absorption may contribute to dehydration of CF distal airways. |
first_indexed | 2024-12-18T01:02:58Z |
format | Article |
id | doaj.art-92d4289f20614c0caea8785b60305bdb |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-12-18T01:02:58Z |
publishDate | 2021-10-01 |
publisher | Elsevier |
record_format | Article |
series | Cell Reports |
spelling | doaj.art-92d4289f20614c0caea8785b60305bdb2022-12-21T21:26:18ZengElsevierCell Reports2211-12472021-10-01371109795cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swineXiaojie Luan0Yen Le1Santosh Jagadeeshan2Brendan Murray3James L. Carmalt4Tanya Duke5Shannon Beazley6Masako Fujiyama7Kurtis Swekla8Bridget Gray9Monique Burmester10Veronica A. Campanucci11Alan Shipley12Terry E. Machen13Julian S. Tam14Juan P. Ianowski15Department of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Large Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Small Animal Clinical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaAnimal Care and Research Support, Research Excellence and Innovation, University of Saskatchewan, Saskatoon, SK, CanadaAnimal Care and Research Support, Research Excellence and Innovation, University of Saskatchewan, Saskatoon, SK, CanadaAnimal Care Unit, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada; Respiratory Research Centre, University of Saskatchewan, Saskatoon, SK, CanadaApplicable Electronics, LLC, New Haven, CT, USADepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USADepartment of Medicine, Division of Respirology, Critical Care, and Sleep Medicine, Royal University Hospital, University of Saskatchewan, Saskatoon, SK, Canada; Respiratory Research Centre, University of Saskatchewan, Saskatoon, SK, CanadaDepartment of Anatomy Physiology and Pharmacology, University of Saskatchewan, Saskatoon, SK, Canada; Respiratory Research Centre, University of Saskatchewan, Saskatoon, SK, Canada; Corresponding authorSummary: A controversial hypothesis pertaining to cystic fibrosis (CF) lung disease is that the CF transmembrane conductance regulator (CFTR) channel fails to inhibit the epithelial Na+ channel (ENaC), yielding increased Na+ reabsorption and airway dehydration. We use a non-invasive self-referencing Na+-selective microelectrode technique to measure Na+ transport across individual folds of distal airway surface epithelium preparations from CFTR−/− (CF) and wild-type (WT) swine. We show that, under unstimulated control conditions, WT and CF epithelia exhibit similar, low rates of Na+ transport that are unaffected by the ENaC blocker amiloride. However, in the presence of the cyclic AMP (cAMP)-elevating agents forskolin+IBMX (isobutylmethylxanthine), folds of WT tissues secrete large amounts of Na+, while CFTR−/− tissues absorb small, but potentially important, amounts of Na+. In cAMP-stimulated conditions, amiloride inhibits Na+ absorption in CFTR−/− tissues but does not affect secretion in WT tissues. Our results are consistent with the hypothesis that ENaC-mediated Na+ absorption may contribute to dehydration of CF distal airways.http://www.sciencedirect.com/science/article/pii/S2211124721012559ENaCCFTRcystic fibrosisCFairway dehydrationdistal airways |
spellingShingle | Xiaojie Luan Yen Le Santosh Jagadeeshan Brendan Murray James L. Carmalt Tanya Duke Shannon Beazley Masako Fujiyama Kurtis Swekla Bridget Gray Monique Burmester Veronica A. Campanucci Alan Shipley Terry E. Machen Julian S. Tam Juan P. Ianowski cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine Cell Reports ENaC CFTR cystic fibrosis CF airway dehydration distal airways |
title | cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine |
title_full | cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine |
title_fullStr | cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine |
title_full_unstemmed | cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine |
title_short | cAMP triggers Na+ absorption by distal airway surface epithelium in cystic fibrosis swine |
title_sort | camp triggers na absorption by distal airway surface epithelium in cystic fibrosis swine |
topic | ENaC CFTR cystic fibrosis CF airway dehydration distal airways |
url | http://www.sciencedirect.com/science/article/pii/S2211124721012559 |
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