The handling of five catecholamines by the extraneuronal O-methylating system of the rat heart

In a comparative study, the handling of five catecholamines by the extraneuronal O-methylating system of the rat heart was determined; all rats were pretreated with reserpine, monoamine oxidase and neuronal uptake were inhibited in all experiments. Hearts were perfused for 7 min with a tracer concentration of 3H-(+/-)-isoprenaline, either in the absence or in the presence of unlabelled catecholamines (which reduced the O-methylation of the tracer amine). IC50's were determined for unlabelled catecholamines and then converted to "half-saturating outside concentrations", i.e., to those concentrations in the perfusion fluid that half-saturate the intracellular catechol-O-methyl transferase (COMT). The values for the (-)-isomers of dobutamine, isoprenaline, adrenaline and noradrenaline and that for dopamine were low and rather similar (between 0.67 and 2.7 mumol/l). Stereoselectivity for isoprenaline probably reflected the preference of uptake2 for the (-)-isomer. The effects of (-)- and (+)-dobutamine indicated that both isomers are a) transported by uptake2 and b) good substrates of COMT. The Vmax for O-methylation determined for 3H-(+/-)-isoprenaline, 3H-(+/-)-adrenaline, 3H-(+/-)-noradrenaline and 3H-dopamine] was rather similar for all four catecholamines. It is concluded that the extraneuronal O-methylating system of the rat heart handles the five catecholamines in a similar manner, although the Km for uptake2 had been found to increase substantially in the order: dobutamine less than isoprenaline less than adrenaline less than noradrenaline less than dopamine (Grohmann and Trendelenburg 1984b).