Uptake and metabolism of catecholamines in the perfused hearts of different species

Abstract

1 The uptake of (±)-³H-noradrenaline was studied in isolated perfused hearts of rat, mouse, guinea-pig, pigeon and toad (Bufo marinus), and the IC50 (concentration causing 50% inhibition) values for inhibition of uptake of (±)-³H-noradrenaline by (–)-noradrenaline were calculated. IC50 values ranging from 0·28 μm (rat heart) to 2·34 μm (toad heart) were found. 2 In all species except the toad, (–)-noradrenaline showed a higher affinity than (–)-adrenaline for the uptake process, but the reverse was found for the toad heart. 3 Mouse and pigeon hearts contained increasing amounts of metabolites of noradrenaline with increasing perfusion concentrations of noradrenaline, but the guinea-pig and toad hearts did not. The in vitro activities of noradrenaline catabolizing enzymes in heart homogenates were measured but did not explain the differences in the pattern of catabolism of noradrenaline found in the intact hearts of the different species. 4 In all hearts except the toad, cocaine was an effective blocking agent for the uptake of (±)-³H-noradrenaline and led to an increase in ³H-normetanephrine in these hearts. In the pigeon heart, cocaine plus phenoxybenzamine in the perfusate resulted in an inhibition of both ³H-noradrenaline uptake and ³H-normetanephrine formation. 5 In guinea-pig and pigeon perfused hearts, the uptake of ³H-noradrenaline into atria and ventricles reflected the relative concentrations of endogenous catecholamines in these regions, but this was not found for rat, mouse and toad hearts. 6 It was concluded that species differences exist for both the accumulation and metabolism of catecholamines in isolated perfused hearts.