Document Detail


Inhibition of cystic fibrosis transmembrane conductance regulator chloride channel currents by arachidonic acid.
MedLine Citation:
PMID:  10914639     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chloride permeation through the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel is inhibited by a number of different classes of organic anions which are able to enter and block the channel pore from its cytoplasmic end. Here I show, using patch clamp recording from CFTR-transfected baby hamster kidney cell lines, that the cis-unsaturated fatty acid arachidonic acid also inhibits CFTR Cl- currents when applied to the cytoplasmic face of excised membrane patches. This inhibition was of a relatively high affinity compared with other known CFTR inhibitors, with an apparent Kd of 6.5 +/- 0.9 microM. However, in contrast with known CFTR pore blockers, inhibition by arachidonic acid was only very weakly voltage dependent, and was insensitive to the extracellular Cl- concentration. Arachidonic acid-mediated inhibition of CFTR Cl- currents was not abrogated by inhibitors of lipoxygenases, cyclooxygenases or cytochrome P450, suggesting that arachidonic acid itself, rather than some metabolite, directly affects CFTR. Similar inhibition of CFTR Cl- currents was seen with other fatty acids, with the rank order of potency linoleic > or = arachidonic > or = oleic > elaidic > or = palmitic > or = myristic. These results identify fatty acids as novel high affinity modulators of the CFTR Cl- channel.
Authors:
P Linsdell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  78     ISSN:  0008-4212     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-11-21     Completed Date:  2000-11-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  CANADA    
Other Details:
Languages:  eng     Pagination:  490-9     Citation Subset:  IM    
Affiliation:
Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada. paul.linsdell@dal.ca
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MeSH Terms
Descriptor/Qualifier:
Animals
Arachidonic Acid / pharmacology*
Cell Line
Clotrimazole / pharmacology
Cricetinae
Cyclooxygenase Inhibitors / pharmacology
Cystic Fibrosis Transmembrane Conductance Regulator / drug effects*,  physiology
Fatty Acids / pharmacology*
Growth Inhibitors / pharmacology
Indomethacin / pharmacology
Kidney / cytology,  drug effects*,  physiology
Membrane Potentials / drug effects,  physiology
Nordihydroguaiaretic Acid / pharmacology
Chemical
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Fatty Acids; 0/Growth Inhibitors; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; 23593-75-1/Clotrimazole; 500-38-9/Nordihydroguaiaretic Acid; 506-32-1/Arachidonic Acid; 53-86-1/Indomethacin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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