Document Detail

Purinergic signaling underlies CFTR control of human airway epithelial cell volume.
MedLine Citation:
PMID:  15463893     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Loss of cystic fibrosis transmembrane conductance regulator (CFTR) function in cystic fibrosis (CF) causes dysregulation of multiple ion channels, water channels, and acid-base transporters in epithelia. As such, we hypothesized that dysregulation of many critical ion channels and transporters may cause defects in human airway epithelial cell volume regulation. METHODS: Cell volume, regulatory volume decrease, and its regulation was assessed in real-time via Coulter Counter Multisizer III-driven electronic cell sizing in non-CF, CF, and CFTR-complemented CF human airway epithelial cells. SPQ halide fluorescence assay of hypotonicity-induced chloride efflux provided indirect validation of the cell volume assays. RESULTS: CFTR, via autocrine ATP signaling, governs human airway epithelial cell volume regulation. Non-CF cells and wild-type (WT)-CFTR-transfected CF cells had normal regulatory volume decrease (RVD) responses that were attenuated by blockade of autocrine and paracrine purinergic signaling. In contrast, parental IB3-1 CF cells or IB3-1 cells expressing CFTR mutants (DeltaF508, G551D, and S1455X) failed to RVD. CF cell RVD was rescued by agonists to P2Y G protein-coupled receptors and, more robustly, by agonists to P2X purinergic receptor channels. CONCLUSIONS: Loss of CFTR and CFTR-driven autocrine ATP signaling may underlie defective cell volume regulation and dysregulated ion, water, and acid-base transport in CF airway epithelia.
Gavin M Braunstein; Akos Zsembery; Torry A Tucker; Erik M Schwiebert
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society     Volume:  3     ISSN:  1569-1993     ISO Abbreviation:  J. Cyst. Fibros.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-10-06     Completed Date:  2004-11-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  101128966     Medline TA:  J Cyst Fibros     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  99-117     Citation Subset:  IM    
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
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MeSH Terms
Adenosine Triphosphate / metabolism
Autocrine Communication / physiology
Bronchi / cytology
Calcium / metabolism
Cell Line
Chlorides / metabolism
Cystic Fibrosis / metabolism*
Cystic Fibrosis Transmembrane Conductance Regulator / genetics,  metabolism*
Epithelial Cells / cytology,  metabolism
Gene Expression
Hypotonic Solutions / pharmacology
Isotonic Solutions / pharmacology
Receptors, Purinergic P2 / metabolism*
Respiratory Mucosa / cytology,  metabolism*
Signal Transduction / physiology*
Water-Electrolyte Balance / physiology*
Grant Support
Reg. No./Substance:
0/CFTR protein, human; 0/Chlorides; 0/Hypotonic Solutions; 0/Isotonic Solutions; 0/Receptors, Purinergic P2; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium

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