A KINETIC INVESTIGATION OF THE PULMONARY METABOLISM OF DOPAMINE IN RATS SHOWS MARKED DIFFERENCES COMPARED WITH NORADRENALINE

The aim of this study was to investigate the deamination of dopamine i n the intact pulmonary circulation of isolated lungs of the rat. The f irst part of the study showed that dopamine is not converted to noradr enaline by dopamine-beta-hydroxylase (DBH) when dopamine is perfused t hrough isolated lung preparations with monoamine oxidase (MAO) and cat echol-O-methyltransferase (COMT) inhibited. Hence, it was not necessar y to inhibit DBH in subsequent experiments. The metabolite profile for deamination of dopamine in the lungs was examined by determining whet her MAO and semicarbazide-sensitive amine oxidases (SSAO) contribute t o the deamination of dopamine (and noradrenaline), and by determining the activity of MAO (k(MAO)) for the metabolism of dopamine. Lungs wer e perfused with 1 nmol/l H-3-dopamine or H-3-noradrenaline with COMT i nhibited and, in experiments to determine the contribution of SSAO to acid deamination, with MAO inhibited. Inhibition of MAO reduced the de amination of dopamine and noradrenaline by 99.8% and 98.6%, respective ly, indicating that MAO, and not SSAO, was responsible for deamination of the catecholamines in the lungs. The k(MAO) value for deamination of dopamine was 3.89 min(-1). Further experiments were carried out to determine the contributions of MAO-A and MAO-B to the deamination of d opamine in lungs perfused with 1 nmol/l(3)H-dopamine and 100 nmol/l la zabemide or 300 nmol/l Ro41-1049, respectively. The values of k(MAO-A) and k(MAO-B) were 3.05 min(-1) and 0.626 min(-1), respectively. It wa s concluded that, in rat lungs, MAO-A contributed 78-84% and MAO-B 16- 22% to the total deamination of dopamine and SSAO had no significant r ole in its pulmonary metabolism. These relative contributions of MAO-A and MAO-B to the deamination of dopamine are very similar to those th at have been determined previously for noradrenaline, but the rate con stant for deamination of dopamine is 26-fold greater than that for nor adrenaline in rat lungs.