cAMP-stimulated Na+ transport in H441 distal lung epithelial cells: role of PKA, phosphatidylinositol 3-kinase, and sgk1

Christie P Thomas; Jason R Campbell; Patrick J Wright; Russell F Husted

doi:10.1152/ajplung.00340.2003

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cAMP-stimulated Na+ transport in H441 distal lung epithelial cells: role of PKA, phosphatidylinositol 3-kinase, and sgk1

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cAMP-stimulated Na+ transport in H441 distal lung epithelial cells: role of PKA, phosphatidylinositol 3-kinase, and sgk1

Christie P Thomas, Jason R Campbell, Patrick J Wright and Russell F Husted

American journal of physiology. Lung cellular and molecular physiology, Vol.287(4), pp.L843-L851

10/2004

DOI: 10.1152/ajplung.00340.2003

PMID: 15208094

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Abstract

H441 cells, a bronchiolar epithelial cell line, develop a cAMP-regulated benzamil-sensitive Na+ transport pathway on permeable supports (Itani OA, Auerbach SD, Husted RF, Volk KA, Ageloff S, Knepper MA, Stokes JB, Thomas CP. Am J Physiol Lung Cell Mol Physiol 282: L631-L641, 2002). To understand the molecular basis for the stimulation of Na+ transport, we delineated the role of specific intracellular pathways and examined the effect of cAMP on alphabetagamma-epithelial Na+ channel (ENaC) and sgk1 expression. Na+ transport increases within 5 min of cAMP stimulation and is sustained for >24 h. The sustained effect of cAMP on Na+ transport is abolished by LY-294002, an inhibitor of phosphatidylinositol 3-kinase, by H89, an inhibitor of PKA, or by SB-202190, an inhibitor of p38 MAP kinase. The sustained effect of cAMP was associated with increases in alpha-ENaC mRNA and protein but without a detectable increase in betagamma-ENaC and sgk1. The early effect of cAMP on Na+ transport is brefeldin sensitive and is mediated via PKA. These results are consistent with a model where the early effect of cAMP is to increase trafficking of Na+ channels to the apical cell surface whereas the sustained effect requires the synthesis of alpha-ENaC.

Cyclic AMP-Dependent Protein Kinases - metabolism

Cell Line

Respiratory Mucosa - drug effects

Colforsin - pharmacology

Humans

Lung

Enzyme Inhibitors - pharmacology

Morpholines - pharmacology

Nuclear Proteins - metabolism

Phosphatidylinositol 3-Kinases - metabolism

Sodium Channels - physiology

Sodium - metabolism

1-Methyl-3-isobutylxanthine - pharmacology

Cyclic AMP - physiology

Immediate-Early Proteins

Epithelial Sodium Channels

Dexamethasone - pharmacology

p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors

Respiratory Mucosa - physiology

Biological Transport - drug effects

p38 Mitogen-Activated Protein Kinases - metabolism

Kinetics

Chromones - pharmacology

Protein-Serine-Threonine Kinases - metabolism

Details

Title: Subtitle: cAMP-stimulated Na+ transport in H441 distal lung epithelial cells: role of PKA, phosphatidylinositol 3-kinase, and sgk1
Creators: Christie P Thomas - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA. christie-thomas@uiowa.edu
Jason R Campbell
Patrick J Wright
Russell F Husted
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.287(4), pp.L843-L851
DOI: 10.1152/ajplung.00340.2003
PMID: 15208094
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Publisher: United States
Grant note: DK-54348 / NIDDK NIH HHS HL-71664 / NHLBI NIH HHS R01 DK054348 / NIDDK NIH HHS R01 HL071664 / NHLBI NIH HHS
Language: English
Date published: 10/2004
Academic Unit: Stead Family Department of Pediatrics; Obstetrics and Gynecology; Internal Medicine
Record Identifier: 9983985903902771

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