A search for an 'ouabain-like' substance from the electric organ of Electrophorus electricus which led to arachidonic acid and related fatty acids.
The electric organ of Electrophorus electricus contains substances which inhibit (Na+ + K+)-ATPase activity, the specific binding of [3H]ouabain to purified (Na+ + K+)-ATPase and 86Rb+ uptake by chick cardiac cells in culture. The active organic material was extracted from microsomal membranes. Its purification was carried out by chromatography on Sep-Pak C-18 and thin-layer chromatography. Reverse-phase liquid chromatography and mass spectrometry identified the active material as a mixture of unsaturated fatty acids. Linoleic (18:2), arachidonic (20:4), linolenic (18:3) and docosahexaenoic acids (22:6) contributed to about 60% of the total activity of the active material. The other active substances could be arachidonic analogs, since they have both a lipophilic and carboxylic character. Pure unsaturated fatty acids have been shown to be active in the different biological assays used to analyze the endogenous 'ouabain-like' activity. Linolenic, arachidonic and docosahexaenoic acids were the most active, whereas saturated fatty acids and glyceryl esters or methyl esters of unsaturated fatty acids were inactive. It is possible that in pathological situations in which the level of unsaturated fatty acids increases, these molecules may then act as physiological inhibitors of the sodium pump.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D004557:Electric Organ / Q000032:analysis*; D004593:Electrophorus; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D016718:Arachidonic Acid; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase