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Activation of CFTR trafficking and gating by vasoactive intestinal peptide in human bronchial epithelial cells.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2011 Mar; Vol. 112 (3), pp. 902-8. - Publication Year :
- 2011
-
Abstract
- Cystic fibrosis transmembrane conductance regulator (CFTR) is an apical membrane chloride channel critical to the regulation of fluid, chloride, and bicarbonate transport in epithelia and other cell types. The most common cause of cystic fibrosis (CF) is the abnormal trafficking of CFTR mutants. Therefore, understanding the cellular machineries that transit CFTR from the endoplasmic reticulum to the cell surface is important. Vasoactive intestinal polypeptide (VIP) plays an important role in CFTR-dependent chloride transport. The present study was designed to observe the affection of VIP on the trafficking of CFTR, and channel gating in human bronchial epithelium cells (HBEC). Confocal microscopy revealed CFTR immunofluorescence extending from the apical membrane deeply into the cell cytoplasm. After VIP treatment, apical extension of CFTR immunofluorescence into the cell was reduced and the peak intensity of CFTR fluorescence shifted towards the apical membrane. Western blot showed VIP increased cell surface and total CFTR. Compared with the augmented level of total CFTR, the surface CFTR increased more markedly. Immunoprecipitation founded that the mature form of CFTR had a marked increase in HBEC treated with VIP. VIP led to a threefold increase in Cl(-) efflux in HBEC. Glibenclamide-sensitive and DIDS-insensitive CFTR Cl(-) currents were consistently observed after stimulation with VIP (10(-8) mol/L). The augmentation of CFTR Cl(-) currents enhanced by VIP (10(-8) mol/L) was reversed, at least in part, by the protein kinase A (PKA) inhibitor, H-89 and the protein kinase C (PKC) inhibitor, H-7, suggesting PKA and PKC participate in the VIP-promoted CFTR Cl(-) currents.<br /> (Copyright © 2010 Wiley-Liss, Inc.)
- Subjects :
- Cell Line
Chlorides metabolism
Colforsin pharmacology
Humans
Ion Channel Gating
Membrane Potentials drug effects
Ozone pharmacology
Patch-Clamp Techniques
Protein Kinase Inhibitors pharmacology
Protein Transport
Vasoactive Intestinal Peptide pharmacology
Bronchi cytology
Cell Membrane metabolism
Cystic Fibrosis Transmembrane Conductance Regulator metabolism
Epithelial Cells metabolism
Vasoactive Intestinal Peptide physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4644
- Volume :
- 112
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 21328463
- Full Text :
- https://doi.org/10.1002/jcb.22999