Novel role for CFTR in fluid absorption from the distal airspaces of the lung.

Détails

ID Serval
serval:BIB_0061E9E828CC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Novel role for CFTR in fluid absorption from the distal airspaces of the lung.
Périodique
Journal of General Physiology
Auteur(s)
Fang X., Fukuda N., Barbry P., Sartori C., Verkman A.S., Matthay M.A.
ISSN
0022-1295
Statut éditorial
Publié
Date de publication
2002
Peer-reviewed
Oui
Volume
119
Numéro
2
Pages
199-207
Langue
anglais
Notes
Publication types: Comparative Study ; In Vitro ; Journal Article
Résumé
The active absorption of fluid from the airspaces of the lung is important for the resolution of clinical pulmonary edema. Although ENaC channels provide a major route for Na(+) absorption, the route of Cl(-) transport has been unclear. We applied a series of complementary approaches to define the role of Cl(-) transport in fluid clearance in the distal airspaces of the intact mouse lung, using wild-type and cystic fibrosis Delta F508 mice. Initial studies in wild-type mice showed marked inhibition of fluid clearance by Cl(-) channel inhibitors and Cl(-) ion substitution, providing evidence for a transcellular route for Cl(-) transport. In response to cAMP stimulation by isoproterenol, clearance was inhibited by the CFTR inhibitor glibenclamide in both wild-type mice and the normal human lung. Although isoproterenol markedly increased fluid absorption in wild-type mice, there was no effect in Delta F508 mice. Radioisotopic clearance studies done at 23 degrees C (to block active fluid absorption) showed approximately 20% clearance of (22)Na in 30 min both without and with isoproterenol. However, the clearance of (36)Cl was increased by 47% by isoproterenol in wild-type mice but was not changed in Delta F508 mice, providing independent evidence for involvement of CFTR in cAMP-stimulated Cl(-) transport. Further, CFTR played a major role in fluid clearance in a mouse model of acute volume-overload pulmonary edema. After infusion of saline (40% body weight), the lung wet-to-dry weight ratio increased by 28% in wild-type versus 64% in Delta F508 mice. These results provide direct evidence for a functionally important role for CFTR in the distal airspaces of the lung.
Mots-clé
Absorption/physiology, Animals, Bronchodilator Agents/pharmacology, Chloride Channels/antagonists &amp, inhibitors, Chloride Channels/metabolism, Cystic Fibrosis/genetics, Cystic Fibrosis/metabolism, Cystic Fibrosis Transmembrane Conductance Regulator/antagonists &amp, inhibitors, Cystic Fibrosis Transmembrane Conductance Regulator/genetics, Humans, Isotonic Solutions/pharmacokinetics, Lung/drug effects, Lung/physiology, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Pulmonary Edema/genetics, Pulmonary Edema/metabolism, Sodium Chloride/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/02/2008 16:02
Dernière modification de la notice
08/05/2019 13:38
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