Effect of adrenochrome on calcium accumulation by heart mitochondria

Abstract

The effects of adrenochrome (1–100 μg/ml or 5.6 × 10 −6 to 5.6 × 10 −4 M) on calcium binding, calcium uptake, and ATPase activities of rat heart mitochondria were investigated. Depression, by adrenochrome, of mitochondrial calcium binding and uptake was observed under in vitro conditions, whereas mitochondrial ATPase activity was not altered appreciably. The inhibitory effect of adrenochrome on calcium uptake activity was independent of the pH of the incubation medium, but it was dependent upon the dose of drug and the time of incubation. High concentrations of calcium in the incubation medium antagonized the adrenochrome-induced depression. The inhibition of mitochondrial calcium uptake by adrenochrome was of a mixed type. Furthermore, the depressed calcium uptake activity was observed after washing adrenochrome-treated mitochondria with buffer. Significant decreases in calcium accumulating activities were also seen in mitochondria isolated from hearts perfused with various concentrations of adrenochrome (5–50 μg/ml) for 10 min, or with 50 μg/ml adrenochrome for various time periods. Contractile force of the perfused rat heart with various concentrations of adrenochrome (5–50, μg/ml) decreased in a dose-dependent manner. It is suggested that the cardiac contractile failure and myocardial cell necrosis induced by adrenochrome may partly be due to its inhibitory effect on the calcium accumulating ability of mitochondria.