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Cardiac Sodium, Potassium-Adenosine Triphosphatase as a Possible Site of Adriamycin-induced Cardiotoxicity¹

Department of Biochemistry, University of South Florida, College of Medicine, Tampa, Florida 33612

Adriamycin was tested as a possible inhibitor of cardiac sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase). At concentrations of 10^-4 M and lower, Adriamycin had no effect upon either ouabain-sensitive (Na-K-ATPase) or ouabain-insensitive adenosine triphosphatase activity in homogenates and microsomal fractions of cardiac tissue from several different species. Adriamycin inhibited adenosine triphosphatase activity at a concentration of 10^-3 M, but this was due to the inhibition of ouabain-insensitive adenosine triphosphatase rather than to inhibition of Na-K-ATPase. Under no condition was an inhibition of Na-K-ATPase activity by Adriamycin observed. These conditions included preincubation of the enzyme with Adriamycin, chelation of Ca²⁺, addition of reduced nicotinamide adenine dinucleotide phosphate, and variation of buffer and pH. It was concluded that Na-K-ATPase is not a likely site of Adriamycin-induced cardiotoxicity.

¹ This research was supported in part by a grant from the American Heart Association, Florida Affiliate.

² To whom requests for reprints should be addressed, at the Department of Biochemistry, University of South Florida College of Medicine, 12901 North 30th Street, Tampa, Fla. 33612.

³ Supported by an R. G. Thompson Fellowship from the American Cancer Society.

⁴ Deceased.

Received 2/ 4/80. Accepted 11/ 4/80.