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Uptake kinetics and metabolism of 7–3H‐dopamine in the isolated perfused rat heart

1 The isolated, perfused rat heart accumulates dopamine by two distinct uptake mechanisms characterized by different kinetic constants and different patterns of metabolite production (Uptake 1: Km 0.69 × 10−6M and Vmax (1.45 × 10−9 mol/g)/min; Uptake 2: Km 5.9 × 10−4M and Vmax (0.14 × 10−6 mol/g)/min). 2 The metabolic fate of dopamine taken up by the isolated, perfused rat heart depends on the concentration of dopamine in the perfusion medium. At a very low perfusion concentration (0.047 × 10−10 mol/ml) most of the radioactivity is stored as unchanged dopamine and the main metabolite is noradrenaline. With increasing perfusion concentrations deamination becomes the main metabolic pathway, deaminated metabolites accounting for more than 50% of the total radioactivity after perfusion with 2,614.4 × 10−10 mol/ml for 16 minutes. The O‐methylated, and the O‐methylated deaminated metabolites are of minor importance at all perfusion concentrations. 3 The resistance to wash out of the dopamine taken up by the isolated, perfused rat heart is dependent on the perfusion concentration used. At a concentration of 66.9 × 10−10 mol/ml, 50% of the total activity is washed out during an 8 min wash period. Within the same time interval there is no wash out when a perfusion concentration of 0.042 × 10−10 mol/ml is used. 4 It is concluded that the metabolic fate of dopamine taken up at various perfusion concentrations reflects the distribution of dopamine within intra‐ and extraneuronal compartments in the hearts.