Fatty acid-induced modulation of ouabain responsiveness of rat Na, K-ATPase isoforms.
Membrane phospholipids represent a potential influence on the enzymatic properties of the Na,K-ATPase. Little is known concerning the effects of the fatty acid environment surrounding the enzyme on the kinetic properties of the Na,K-ATPase. We used the most obvious difference among the alpha isoforms of rat, their affinities for digitalis glycosides, to examine the relationship between the lipid environment and the Na,K-ATPase. Specific membrane environments that differ in their fatty acid composition were produced by drug-induced diabetes, as well as variations in diet. The alpha1 isoforms in various tissues were then characterized by their resistance to ouabain in Na,K-ATPase-enriched membrane microsomal fractions. The Na,K-ATPase activity in nerves and hearts were altered by diabetes and partially restored in nerves after a fish oil diet. Evaluation of enzyme kinetics (dose-response curves for ouabain) in membrane preparations allowed us to correlate the ouabain affinity of alpha1 isoform with fatty acid composition. The affinity of the alpha1 isoform for ouabain was significantly increased with accretions in the total amount of fatty acids of the n-6 series (P < 0.0001). Our observations provide a partial explanation for the observed difference in isoform properties among tissues. Moreover, these results underline the interaction between membrane fatty acids and the glycoside binding site of the Na,K-ATPase alpha1 subunit.
Laboratoire de Recherche Cardiologique, Faculté de Médecine, 15 Bd Pierre Dramard 13015, Marseille, France.
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Gerbi
J M
JM
Maixent
D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004041:Dietary Fats / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology; D008297:Male; D008563:Membrane Lipids / Q000032:analysis / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D000069463:Olive Oil; D009928:Organ Specificity; D010042:Ouabain / Q000494:pharmacology*; D010938:Plant Oils / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013311:Streptozocin
D004041:Dietary Fats; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D008563:Membrane Lipids; D009419:Nerve Tissue Proteins; D000069463:Olive Oil; D010938:Plant Oils; D020033:Protein Isoforms; D004281:Docosahexaenoic Acids; D010042:Ouabain; D013311:Streptozocin; D015118:Eicosapentaenoic Acid; D000254:Sodium-Potassium-Exchanging ATPase