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Dopamine and adrenaline, but not isoprenaline, are substrates for uptake and metabolism in isolated perfused lungs of rats

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Summary

The uptake and subsequent metabolism by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) of dopamine, adrenaline, isoprenaline and noradrenaline in isolated perfused lungs of rats has been examined. In lung preparations in which COMT and MAO were inhibited, the uptake of 3H-labelled dopamine, (−)-adrenaline and (−)-noradrenaline, but not (±)-isoprenaline, was reduced by cocaine (10 or 100 μmol/l) The rank order of the Km values of the amines that were substrates for uptake in the lungs were: dopamine (0.246 μmol/l) < noradrenaline (0.967 μmol/l) < adrenaline (3.32 μmol/l). These results are consistent with transport of catecholamines in rat lungs by Uptake1.

In lung preparations with COMT and MAO intact, dopamine and noradrenaline were removed from the circulation (50% and 32%, respectively) and mainly metabolized. There was very little (3.0%) removal of isoprenaline by the lungs and adrenaline was not included in this part of the study. In lung preparations in which only MAO was inhibited, the rank order of COMT activity for O-methylation of the amines was dopamine ≪ noradrenaline ≥ adrenaline (kCOMT values: 4.98 min−1, 0.357 min−1, and 0.234 min−1, respectively).

If dopamine or adrenaline are perfused through the pulmonary circulation in isolated lungs of the rat, they are taken up and then metabolized by COMT and MAO, as also occurs for noradrenaline. Isoprenaline is not a substrate for uptake in the lungs. There was less uptake of adrenaline than noradrenaline, indicating that uptake and metabolism in the lungs may not be a significant removal process for adrenaline in the circulation of rats in vivo. The more marked uptake of dopamine (than of noradrenaline) indicates that uptake and metabolism by the lungs, at least in the rat, may play an important role in the removal of dopamine from the circulation in vivo.

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Abbreviations

COMT:

catechol-O-methyltransferase

DOMA:

3,4-dihydroxymandelic acid

DOPAC:

3,4-dihydroxyphenylacetic acid

DOPEG:

3,4-dihydroxyphenylglycol

DOPET:

3,4-dihydroxyphenyl ethanol

MAO:

monoamine oxidase

MN:

metanephrine

MTA:

3-methoxytyramine

NMN:

normetanephrine

OMDA:

O-methylated deaminated metabolites

OMI:

3-O-methylisoprenaline

U-0521:

3,4-dihydroxy-2-methylpropiophenone

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, The University of Queensland, 4072, Brisbane, Queensland, Australia

    Lesley J. Bryan-Lluka & Stella R. O'Donnell

Authors
  1. Lesley J. Bryan-Lluka
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  2. Stella R. O'Donnell
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Additional information

Some of the results of this study were presented to the Australasian Society of Clinical and Experimental Pharmacologists (Bryan and O'Donnell 1987, 1988; Bryan et al. 1989; Bryan-Lluka 1990)

Send offprint requests to L.J. Bryan-Lluka at the above address

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Bryan-Lluka, L.J., O'Donnell, S.R. Dopamine and adrenaline, but not isoprenaline, are substrates for uptake and metabolism in isolated perfused lungs of rats. Naunyn-Schmiedeberg's Arch Pharmacol 346, 20–26 (1992). https://doi.org/10.1007/BF00167565

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  • DOI: https://doi.org/10.1007/BF00167565

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