The relation between the subcellular distribution of [3H]reserpine and its proposed site of action

Abstract

The amount of [3H]reserpine retained after injection is greater in the heart, a tissue with a high density of adrenergic innervation than in femoral muscle. Subcellular distribution studies emphasized that 15 and 60 min after injection of [3H]reserpine it could not be shown to be uniquely associated with the noradrenaline-containing granules. The possibility existed that the large amount of reserpine bound to cellular lipids at these times might mask a more specific binding. A reduction in the dose and a lengthening of the time between drug administration and tissue measurement to 18 h revealed a small amount of [3H]reserpine to be bound more firmly to the microsomal or amine granule-containing fraction. Prior saturation of tissue binding sites by treatment with large amounts of unlabelled reserpine or tetrabenazine decreased the retention of subsequently injected [3H]reserpine. This decreased tissue retention resulted in an increase in the formation of [3H]trimethoxybenzoic acid. A model is proposed relating tissue distribution and binding to reserpine's mechanism of action.