Effects of 8-cpt-cAMP on the epithelial sodium channel expressed in Xenopus oocytes

Details

Serval ID
serval:BIB_4119CB65AFD2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Effects of 8-cpt-cAMP on the epithelial sodium channel expressed in Xenopus oocytes
Journal
Journal of Membrane Biology
Author(s)
Chraibi  A., Schnizler  M., Clauss  W., Horisberger  J. D.
ISSN
0022-2631 (Print)
Publication state
Published
Issued date
09/2001
Volume
183
Number
1
Pages
15-23
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep 1
Abstract
Vasopressin stimulates the activity of the epithelial Na channel (ENaC) through the cAMP/PKA pathway in the cortical collecting tubule, or in similar amphibian epithelia, but the mechanism of this regulation is not yet understood. This stimulation by cAMP could not be reproduced with the rat or Xenopus ENaC expressed in Xenopus oocyte. Recently, it was shown that the alpha-subunit cloned from the guinea-pig colon (alpha gp) could confer the ability to be activated by the membrane-permeant cAMP analogue 8-chlorophenyl-thio-cAMP (cpt-cAMP) to channels produced by expression of alpha gp, beta rat and gamma rat ENaC subunits. In this study we investigate the mechanism of this activation. Forskolin treatment, endogenous production of cAMP by activation of coexpressed beta adrenergic receptors, or intracellular perfusion with cAMP did not increase the amiloride-sensitive Na current, even though these maneuvers stimulated CFTR (cystic fibrosis transmembrane conductance regulator)-mediated Cl currents. In contrast, extracellular 8-cpt-cAMP increased alpha gp, beta rat and gamma rat ENaC activity but had no effect on CFTR. Swapping intracellular domains between the cpt-cAMP-sensitive alpha gp and the cpt-cAMP-resistant alpha rat-subunit showed that neither the N-terminal nor the C-terminal of alpha ENaC was responsible for the effect of cpt-cAMP. The mechanisms of activation of ENaC by cpt-cAMP and of CFTR by the cAMP/PKA pathway are clearly different. cpt-cAMP seems to increase the activity of ENaC formed by alpha gp and beta gamma rat by interacting with the extracellular part of the protein.
Keywords
Amiloride/pharmacology Animals Carrier Proteins/pharmacology Cyclic AMP/*analogs & derivatives/metabolism/*pharmacology Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors Cystic Fibrosis Transmembrane Conductance Regulator/genetics/metabolism Electrophysiology Enzyme Inhibitors/pharmacology Epithelial Sodium Channel Gene Expression Guinea Pigs Humans Intracellular Fluid/metabolism *Intracellular Signaling Peptides and Proteins Oocytes/drug effects/metabolism Peptide Fragments/pharmacology Rats Sodium Channels/*drug effects/genetics/metabolism/physiology Thionucleotides/metabolism/*pharmacology Xenopus
Pubmed
Web of science
Create date
24/01/2008 12:38
Last modification date
20/08/2019 13:40
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