SUBCELLULAR SITES OF THE CATECHOLAMINE-DEPLETING ACTION OF RESERPINE IN THE HEART

¹ Department of Pharmacology, College of Medical Sciences, University of Minnesota, Minneapolis, Minnesota

The isolated cat heart was perfused for 30, 60 or 90 min with and without a reserpine-containing (5 µg/ml) solution. Portions of the atria and left ventricle were homogenized and separated by differential centrifugation into three fractions: a "coarse" (2,000 x for 5 min) sediment, a "particulate" (105,000 x for 60 min) sediment and a "soluble" (high speed supernatant) fraction. Homogenates and fractions were analyzed for their contents of catecholamines. During the first 30 min of perfusion, reserpine induced a significant degree of depletion of catecholamines only in the soluble fractions of both atria and left ventricle. This was accompanied by an increase in heart rate. Perfusion for 60 or 90 min with reserpine resulted in a more marked depletion of catecholamines in the particulate fractions and a relativeincrease in the level of these amines in the soluble fractions of atria and ventricle. Cocaine, at concentrations of 20 and 40 µg/ml, failed to prevent the catecholamine-depleting action of reserpine. This finding differs from previous studies in which tyramine was used as the depleting agent. It is concluded, therefore, that reserpine and tyramine exert their catecholamine-depleting effects through different mechanisms. It is suggested that reserpine has at least two actions at the subcellular level. The first of these is tyramine-like, i.e., mobilization of catecholamines from the soluble fraction. This is accompanied by sympathomimetic activity. The second is predominantly a depleting effect on the particulate fraction and only becomes apparent after the first. This action is not accompanied by sympathomimetic activity.