A search for endogenous Na+,K+-ATPase inhibitor in acutely volume-expanded hog plasma led to lysophosphatidylcholine gamma-stearoyl.
An Na+,K+-ATPase inhibitor possessing inhibitory activity against the specific binding of ouabain to Na+,K+-ATPase has been purified from the plasma of acutely saline-infused hogs. The purification was performed by a combination of Amberlite XAD-2 adsorption chromatography and five steps of high-pressure liquid chromatography (HPLC). Fast atom bombardment mass and proton nuclear magnetic resonance (NMR) spectrometric studies identified the purified substance as lysophosphatidylcholine gamma-stearoyl (LPCS). The ouabain-displacing activity in plasma, due to this compound, increased with time during saline infusion. The maximal level reached was approximately 12 times higher than that in the pre-infusion plasma sample. Lysophosphatidylcholines (LPCs) containing myristoyl, palmitoyl and oleoyl groups were also inhibitory to Na+,K+-ATPase and ouabain-binding to the enzyme. These LPCs were effective at 100 mumol/l concentrations in attaining 50% inhibition of the enzyme activity and ouabain-binding activity of Na+,K+-ATPase. These results suggest that LPCs containing long chain fatty acids could play an important role as a Na+,K+-ATPase inhibitors under volume-expanded conditions.
D000818:Animals; D001798:Blood Proteins; D008244:Lysophosphatidylcholines / Q000097:blood / Q000302:isolation & purification*; D010042:Ouabain / Q000378:metabolism; D010953:Plasma Volume / Q000187:drug effects*; D011506:Proteins; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D012965:Sodium Chloride / Q000494:pharmacology; D013552:Swine; D000097795:ATPase Inhibitory Protein
D001798:Blood Proteins; D008244:Lysophosphatidylcholines; D010042:Ouabain; D011506:Proteins; D006180:Proton-Translocating ATPases; D012965:Sodium Chloride; D000097795:ATPase Inhibitory Protein