Adrenochrome uptake and its subcellular distribution were examined using isolated perfused rat heart preparation. The heart was perfused for 30 min with a medium containing 1 to 50 mg/l of 14C-adrenochrome and the subcellular fractions were isolated to measure their radioactivities. A decline in contractile force, a rise in resting tension and an increase in
adrenochrome uptake by the heart were seen to depend upon the time of perfusion and the concentration of
adrenochrome in the medium. The sarcolemmal fraction had the highest uptake of
adrenochrome and this was followed by the microsomal fraction; some accumulation of
adrenochrome was also observed in the myofibrillar and mitochondrial fractions. Either 10 or 20 min reperfusion of the heart previously exposed to 25 mg/l of
adrenochrome, resulted in approximately 50 or 37% of the radioactivity remaining in the heart; this indicates irreversible binding of
adrenochrome to the tissue. Reperfusion of the heart showed restoration of the resting tension but the contractile force did not show any recovery.
Propranolol and
iproniazid, which have been shown to inhibit the
adrenochrome induced
cardiotoxicity, reduced
adrenochrome uptake by the heart, and prevented
adrenochrome-induced depression in contractile force and rise in resting tension. These results indicate that
adrenochrome is taken up by the heart and induces cardiac disturbances through its action on different subcellular organelles in the myocardium.