A kinetic investigation of the pulmonary metabolism of dopamine in rats shows marked differences compared with noradrenaline

Scarcella D.L. and Bryan-Lluka L.J. (1995) A kinetic investigation of the pulmonary metabolism of dopamine in rats shows marked differences compared with noradrenaline. Naunyn-Schmiedeberg's Archives of Pharmacology, 351 5: 491-499. doi:10.1007/BF00171040


Author Scarcella D.L.
Bryan-Lluka L.J.
Title A kinetic investigation of the pulmonary metabolism of dopamine in rats shows marked differences compared with noradrenaline
Journal name Naunyn-Schmiedeberg's Archives of Pharmacology   Check publisher's open access policy
ISSN 0028-1298
Publication date 1995-01-01
Sub-type Article (original research)
DOI 10.1007/BF00171040
Open Access Status
Volume 351
Issue 5
Start page 491
End page 499
Total pages 9
Publisher Springer-Verlag
Subject 3004 Pharmacology
Abstract 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-β-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 I 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/1 lazabemide or 300 nmol/I Ro41-1049, respectively. The values of kMAO-A and kMAO-B were 3.05 min-1 and 0.626 min-1, respectively. It was 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 role in its pulmonary metabolism. These relative contributions of MAO-A and MAO-B to the deamination of dopamine are very similar to those that have been determined previously for noradrenaline, but the rate constant for deamination of dopamine is 26-fold greater than that for noradrenaline in rat lungs.
Keyword Dopamine
Kinetics
Monoamine oxidase-A
Monoamine oxidase-B
Rat lungs
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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