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 in the intact pulmonary circulation of isolated lungs of the rat. The first part of the study showed that dopamine is not converted to noradrenaline by dopamine-beta-hydroxylase (DBH) when dopamine is perfused through isolated lung preparations with monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited. Hence, it was not necessary to inhibit DBH in subsequent experiments. The metabolite profile for deamination of dopamine in the lungs was examined by determining whether MAO and semicarbazide-sensitive amine oxidases (SSAO) contribute to the deamination of dopamine (and noradrenaline), and by determining the activity of MAO (kMAO) for the metabolism of dopamine. Lungs were perfused with 1 nmol/l 3H-dopamine or 3H-noradrenaline with COMT inhibited and, in experiments to determine the contribution of SSAO to deamination, with MAO inhibited. Inhibition of MAO reduced the deamination of dopamine and noradrenaline by 99.8% and 98.6%, respectively, indicating that MAO, and not SSAO, was responsible for deamination of the catecholamines in the lungs. The kMAO 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 dopamine in lungs perfused with 1 nmol/l 3H-dopamine and 100 nmol/l lazabemide or 300 nmol/l Ro41-1049, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Scarcella
D L
DL
Department of Physiology and Pharmacoloogy, University of Queensland, Brisbane, Australia.
Bryan-Lluka
L J
LJ
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010293:Pargyline / Q000494:pharmacology; D011652:Pulmonary Circulation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D010293:Pargyline; D004298:Dopamine; D009638:Norepinephrine