Effect of pretreatment with 6‐hydroxydopamine on the uptake and metabolism of catecholamines by the isolated perfused rat heart

1 Isolated rat hearts from control and 6‐hydroxydopamine pretreated animals were perfused with 3H‐noradrenaline or 3H‐dopamine, either at a low perfusion concentration (1.50 × 10−10 mol/ml 3H‐dopamine; 1.18 × 10−10 mol/ml 3H‐noradrenaline) or a high perfusion concentration (296.69 × 10−10 mol/ml 3H‐noradrenaline, 327.45 × 10−10 mol/ml 3H‐dopamine) for 8 minutes. 2 At the low perfusion concentration, the total activity, the radioactivity in the alumina eluates (sum of 3H‐dopamine, 3H‐noradrenaline and deaminated catechol metabolites) and the concentration of 3H‐dopamine, 3H‐noradrenaline and the deaminated catechol metabolites were decreased in the hearts of the pretreated rats as compared with the controls. The O‐methylated amine metabolites were increased. The deaminated O‐methylated metabolites were increased in the experiments with 3H‐noradrenaline and decreased in the 3H‐dopamine experiments. 3 Uptake of 3H‐dopamine and 3H‐noradrenaline by the hearts of 6‐hydroxydopamine pretreated rats was decreased to a much smaller extent when perfused with the high concentration than with the low concentration. 4 At the high perfusion concentration there was a significant difference between control and pretreated animals with regard to the total radioactivity and the radioactivity in the alumina eluates only. The absolute and relative amounts of metabolites were not significantly changed by pretreatment with the exception of the deaminated catechol metabolites in the 3H‐dopamine experiments. 5 It is concluded that neuronal Uptake 1 is greatly impaired in the hearts from rats pretreated with 6‐hydroxydopamine, but extraneuronal Uptake 2 remains intact.