Cardiac sodium, potassium-adenosine triphosphatase as a possible site of adriamycin-induced cardiotoxicity.
Adriamycin ws 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.
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000818:Animals; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology* / Q000633:toxicity; D008274:Magnesium; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D010042:Ouabain; D004317:Doxorubicin; D000251:Adenosine Triphosphatases; D000254:Sodium-Potassium-Exchanging ATPase; D008274:Magnesium