Molecular Pharmacology, Vol 10, 119-129, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

The Influence of Dichlorodiphenyltrichloroethane, Polychlorinated Biphenyls and Anionic Amphiphilic Compounds on Stabilization of Sodium- and Potassium-Activated Adenosine Triphosphatases by Acidic Phospholipids

¹ Pathologic Physiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Dichlorodiphenyltrichloroethane (DDT), extensively chlorinated biphenyls, deoxycholate, and phospholipase A inhibited beef brain and rabbit kidney (Na⁺ + K⁺)-ATPases (EC 3.6.1.3). Phosphatidylserine or phosphatidylinositol but not phosphatidylcholine or phosphatidylethanolamine prevented or reversed the inactivation of the enzymes by each of these inhibitors. Albumin protected against and reversed inactivation of (Na⁺ + K⁺)-ATPases by deoxycholate, oleate, or dodecyl sulfate; however, this protein was less effective against inactivation by the extensively chlorinated hydrocarbons. The extent of (Na⁺ + K⁺)-ATPase inactivation by anionic amphiphiles was dependent upon the temperature at which an enzyme-inhibitor mixture was incubated prior to assay, whereas inactivation by chlorinated hydrocarbons was not affected by temperature. Our experiments lead to the hypothesis that acidic phospholipids are necessary for stabilization of the enzyme and that chlorinated hydrocarbons, deoxycholate, and phospholipase A interfere with the stabilization process.

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ACKNOWLEDGMENTS We thank Drs. R. W. Albers and N. K. Wilson for several helpful discussions relevant to this investigation. Dr. P. W. Albro performed gas chromatographic analyses of the Aroclor mixtures.