Fatty acids inhibit apical membrane chloride channels in airway epithelia

Michael P Anderson; Michael J Welsh

doi:10.1073/pnas.87.18.7334

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Fatty acids inhibit apical membrane chloride channels in airway epithelia

Journal article

Open access

Peer reviewed

Fatty acids inhibit apical membrane chloride channels in airway epithelia

Michael P Anderson and Michael J Welsh

Proceedings of the National Academy of Sciences - PNAS, Vol.87(18), pp.7334-7338

09/1990

DOI: 10.1073/pnas.87.18.7334

PMCID: PMC54738

PMID: 1698296

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https://doi.org/10.1073/pnas.87.18.7334View

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Abstract

Apical membrane Cl- channels control the rate of transepithelial Cl- secretion in airway epithelia. cAMP-dependent protein kinase and protein kinase C regulate Cl- channels by phosphorylation; in cystic fibrosis cells, phosphorylation-dependent activation of Cl- channels is defective. Another important signaling system involves arachidonic acid, which is released from cell membranes during receptor-mediated stimulation. Here we report that arachidonic acid reversibly inhibited apical membrane Cl- channels in cell-free patches of membrane. Arachidonic acid itself inhibited the channel and not a cyclooxygenase or lipoxygenase metabolite because (i) inhibitors of these enzymes did not block the response, (ii) fatty acids that are not substrates for the enzymes had the same effect as arachidonic acid, and (iii) metabolites of arachidonic acid did not inhibit the channel. Inhibition occurred only when fatty acids were added to the cytosolic surface of the membrane patch. Unsaturated fatty acids were more potent than saturated fatty acids. Arachidonic acid inhibited Cl- channels from both normal and cystic fibrosis cells. These results suggest that fatty acids directly inhibit apical membrane Cl- channels in airway epithelial cells.

Membrane Potentials - drug effects

Cystic Fibrosis - physiopathology

Humans

Cells, Cultured

Fatty Acids, Unsaturated - pharmacology

Ion Channels - drug effects

Reference Values

Electric Conductivity

Ion Channels - physiology

Fatty Acids, Nonesterified - pharmacology

Arachidonic Acids - pharmacology

Respiratory Physiological Phenomena

Animals

Chloride Channels

Membrane Proteins - physiology

Dogs

Respiratory System - physiopathology

Epithelium - physiology

Kinetics

Arachidonic Acid

Details

Title: Subtitle: Fatty acids inhibit apical membrane chloride channels in airway epithelia
Creators: Michael P Anderson - Howard Hughes Medical Institute, Department of Internal Medicine and Physiology and Biophysics, University of Iowa College of Medicine, Iowa City 52242
Michael J Welsh
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.87(18), pp.7334-7338
DOI: 10.1073/pnas.87.18.7334
PMID: 1698296
PMCID: PMC54738
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences; United States
Grant note: HL 29851 / NHLBI NIH HHS HL 42385 / NHLBI NIH HHS
Language: English
Date published: 09/1990
Academic Unit: Neurology; Molecular Physiology and Biophysics; Neurosurgery; Internal Medicine
Record Identifier: 9984020713802771

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