The effect of emetine on myocardial catecholamine metabolism

Abstract

Abstract The effects of emetine on the uptake and release of noradrenaline from the isolated, perfused, rat heart and on the in vivo myocardial retention of noradrenaline have been studied. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min−1. The effect of emetine on the uptake of noradrenaline was determined by perfusing hearts for a period of 6 min with perfusate containing various concentrations of emetine and 100 ng ml−1 of [14C]noradrenaline (14C-NA). After 6 min, the emetine-treated hearts contained less (±)−14C-NA than control hearts. The degree of reduction increased with increasing concentrations of emetine. The release of noradrenaline was determined after first perfusing hearts with 14C-NA followed by perfusion with solution containing emetine (0–01 mg ml−1) but free of labelled noradrenaline for periods of 10, 20 and 60 min. It was found that by 60 min emetine significantly decreased myocardial 14C-NA. In the intact animal myocardial concentrations of 14C-NA were reduced 90 min after intravenous 14C-NA, followed immediately by intraperitoneal emetine (1 mg kg−1). These results suggest that the cardiac arrhythmia and irritability seen after emetine treatment in man may be partly due to alterations in catecholamine metabolism.