Linked Life Data

15802612

Source:http://linkedlifedata.com/resource/pubmed/id/15802612

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-5-13
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
999-1005
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15802612-Animals, pubmed-meshheading:15802612-Biological Transport, Active, pubmed-meshheading:15802612-Cystic Fibrosis Transmembrane Conductance Regulator, pubmed-meshheading:15802612-Gene Transfer Techniques, pubmed-meshheading:15802612-Humans, pubmed-meshheading:15802612-Male, pubmed-meshheading:15802612-Mice, pubmed-meshheading:15802612-Mice, Knockout, pubmed-meshheading:15802612-Mice, Transgenic, pubmed-meshheading:15802612-Pulmonary Alveoli, pubmed-meshheading:15802612-Rats, pubmed-meshheading:15802612-Receptors, Adrenergic, beta, pubmed-meshheading:15802612-Receptors, Adrenergic, beta-1, pubmed-meshheading:15802612-Receptors, Adrenergic, beta-2, pubmed-meshheading:15802612-Sodium, pubmed-meshheading:15802612-Sodium Channels, pubmed-meshheading:15802612-Sodium-Potassium-Exchanging ATPase
pubmed:year
2005
pubmed:articleTitle
Interdependency of beta-adrenergic receptors and CFTR in regulation of alveolar active Na+ transport.
pubmed:affiliation
Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural