Effects of adrenochrome on rat heart sarcolemmal ATPase activities

Abstract

Effects of adrenochrome on rat heart sarcolemmal ATPase, calcium binding and adenylate cyclase activities were studied vitro. Adrenochrome (1–100 μg/ml) did not affect calcium binding activity. Significant decreases in adenylate cyclase and Ca 2+ ATPase activities were seen only at a concentration of 100 μg/ml adrenochrome. Adrenochrome depressed Na +−K + ATPase activity in a dose-dependent manner. The inhibitory effect on Na +−K + ATPase of adrenochrome was also observed in sarcolemmal membranes washed with a buffer after treatment with adrenochrome. The percentage inhibition of the enzyme activity was independent over a wide range of pH (6.6–7.8) and concentrations of NaCl/KCl (40/4–100/10,mM/mM). A study on the combined effects of adrenochrome and either ouabain or CaCl 2 showed that, unlike ouabain, calcium produced additive inhibition with adrenochrome. Depression of Na +−K + ATPase activity was also observed in sarcolemma isolated from the heart perfused with adrenochrome. Since adrenochrome has been demonstrated to produce myocardial cell damage and contractile failure in the perfused heart, the present experiments provide a possible explanation for the genesis of adrenochrome-induced cardiotoxicity.