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

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.