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Effect of linoleic acid metabolites on Na(+)/K(+) pump current in N20.1 oligodendrocytes: role of membrane fluidity.
- Source :
-
Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2002 Jul 01; Vol. 182 (1), pp. 76-83. - Publication Year :
- 2002
-
Abstract
- Metabolic derivatives of linoleic acid, both monoepoxides and diols, have been reported to be toxic in humans and multiple animal tissue preparations. A previous electrophysiological study has shown these compounds produce multiple effects on the electrical activity of rat ventricular myocytes. The hydrophobic nature of these compounds suggests the possibility that these effects may be due to nonspecific lipid interactions, i.e., changes in membrane fluidity. This study investigates membrane fluidity as a possible mechanism by which linoleic acid metabolites inhibit Na(+)/K(+) pump current (I(p)). This study showed that positional isomers 9,10- and 12,13-epoxy-octadecenoic acid (EOA) and 9,10- and 12,13-dihydroxy-OA (DHOA) inhibit I(p) in a dose-dependent manner in N20.1 mouse oligodendrocytes, with greater inhibition produced by EOAs. These compounds, at 10 microM, inhibited I(p) by 4.7 +/- 1.6, 18.2 +/- 0.5, 11.7 +/- 0.5, and 25.1 +/- 0.9% for 12,13-DHOA, 9,10-DHOA, 12,13-EOA, and 9,10-EOA, respectively, in oligodendrocytes. Fluorescence recovery after photobleaching measurements showed that both DHOA isomers produced a 7-8% increase in diffusion coefficient of the probe at 10 microM, whereas the diffusion coefficient was decreased by 5 and 13% by 9,10-EOA and 12,13-EOA, respectively. There was no apparent correlation between membrane fluidity and inhibition of I(p) by these four linoleic acid metabolites. These results indicate that membrane fluidity alone cannot explain the effects of these compounds on I(p) and suggest that they have a specific interaction with the Na(+)/K(+) pump.
- Subjects :
- Animals
Fluorescent Dyes chemistry
Linoleic Acids metabolism
Linoleic Acids toxicity
Membrane Fluidity physiology
Mice
Oleic Acids metabolism
Oleic Acids toxicity
Oligodendroglia metabolism
Patch-Clamp Techniques
Sodium-Potassium-Exchanging ATPase metabolism
Spectrometry, Fluorescence
Linoleic Acid metabolism
Linoleic Acid toxicity
Membrane Fluidity drug effects
Oligodendroglia drug effects
Sodium-Potassium-Exchanging ATPase drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0041-008X
- Volume :
- 182
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Toxicology and applied pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 12127265
- Full Text :
- https://doi.org/10.1006/taap.2002.9435