Journal article
Interdependency of β-adrenergic receptors and CFTR in regulation of alveolar active Na+ transport
Circulation research, Vol.96(9), pp.999-1005
2005
DOI: 10.1161/01.RES.0000164554.21993.AC
PMID: 15802612
Abstract
Beta-adrenergic receptors (betaAR) regulate active Na+ transport in the alveolar epithelium and accelerate clearance of excess airspace fluid. Accumulating data indicates that the cystic fibrosis transmembrane conductance regulator (CFTR) is important for upregulation of the active ion transport that is needed to maintain alveolar fluid homeostasis during pulmonary edema. We hypothesized that betaAR regulation of alveolar active transport may be mediated via a CFTR dependent pathway. To test this hypothesis we used a recombinant adenovirus that expresses a human CFTR cDNA (adCFTR) to increase CFTR function in the alveolar epithelium of normal rats and mice. Alveolar fluid clearance (AFC), an index of alveolar active Na+ transport, was 92% greater in CFTR overexpressing lungs than controls. Addition of the Cl- channel blockers NPPB, glibenclamide, or bumetanide and experiments using Cl- free alveolar instillate solutions indicate that the accelerated AFC in this model is due to increased Cl- channel function. Conversely, CFTR overexpression in mice with no beta1- or beta2-adrenergic receptors had no effect on AFC. Overexpression of a human beta2AR in the alveolar epithelium significantly increased AFC in normal mice but had no effect in mice with a non-functional human CFTR gene (Deltaphi508 mutation). These studies indicate that upregulation of alveolar CFTR function speeds clearance of excess fluid from the airspace and that CFTRs effect on active Na+ transport requires the betaAR. These studies reveal a previously undetected interdependency between CFTR and betaAR that is essential for upregulation of active Na+ transport and fluid clearance in the alveolus.
Details
- Title: Subtitle
- Interdependency of β-adrenergic receptors and CFTR in regulation of alveolar active Na+ transport
- Creators
- Gökhan M MUTLU - Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill, United StatesYochai ADIR - Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill, United StatesRajesh BALAGANI - Evanston Northwestern Healthcare Research Institute, Evanston Ill, United StatesGeri TRAVER - University of Iowa College of Medicine, Iowa City, Iowa, United StatesJacob I SZNAJDER - Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill, United StatesPhillip FACTOR - Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY, United StatesMohammed JAMEEL - Evanston Northwestern Healthcare Research Institute, Evanston Ill, United StatesAlexander T AKHMEDOV - Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY, United StatesLynn WELCH - Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill, United StatesVidas DUMASIUS - University of Illinois College of Medicine, Chicago, Ill, United StatesFAN JING MENG - Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY, United StatesJoseph ZABNER - University of Iowa College of Medicine, Iowa City, Iowa, United StatesCraig KOENIG - Evanston Northwestern Healthcare Research Institute, Evanston Ill, United StatesErin Rachel LEWIS - Pulmonary, Allergy, and Critical Care Medicine, Columbia University Medical Center, New York, NY, United States
- Resource Type
- Journal article
- Publication Details
- Circulation research, Vol.96(9), pp.999-1005
- DOI
- 10.1161/01.RES.0000164554.21993.AC
- PMID
- 15802612
- NLM abbreviation
- Circ Res
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Publisher
- Lippincott
- Language
- English
- Date published
- 2005
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094567802771
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