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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Kinetic Interactions of Dopamine and Dobutamine with Human Catechol-O-methyltransferase and Monoamine Oxidase in Vitro

Maohe Yan, Leslie T. Webster Jr. and Jeffrey L. Blumer
Journal of Pharmacology and Experimental Therapeutics April 2002, 301 (1) 315-321; DOI: https://doi.org/10.1124/jpet.301.1.315
Maohe Yan
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Leslie T. Webster Jr.
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Jeffrey L. Blumer
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Abstract

Dopamine and dobutamine are often infused together into acutely ill patients requiring temporary support of cardiac and renal function, but whether these catecholamines affect the metabolic clearance of each other is not established. We determined the kinetics of dopamine and dobutamine as substrates and inhibitors of each other, i.e., apparentVmax, Km, andKi, with crude preparations of human blood mononuclear cell catechol-O-methyltransferase (COMT) and platelet monoamine oxidase (MAO) at pH 7.4 and 37°C. Values of Vmax for dopamine and dobutamine as substrates for COMT were 0.45 and 0.59 nmol of 3-O-methyl product formed per milligram of protein per minute, whereas those for Km were 0.44 and 0.05 mM, respectively. Dopamine and dobutamine were competitive inhibitors of each other in this reaction. TheKi for dopamine as an inhibitor of dobutamine methylation was 1.5 mM, whereas that for dobutamine as an inhibitor of dopamine methylation was 0.015 mM. Dopamine but not dobutamine was a substrate for MAO. TheVmax for dihydroxyphenylacetaldehyde formation from dopamine was 0.29 nmol/mg protein/min and theKm for dopamine was 0.38 mM. Dobutamine was a noncompetitive inhibitor of dopamine oxidation in this reaction (Ki ≅ 1.19 mM). The high apparent Km andKi values derived for dopamine and dobutamine when tested with these two human enzymes in vitro suggest that these catecholamines do not interfere with the metabolism of each other when both are infused together at therapeutic concentrations.

Footnotes

  • Supported in part by Grant 1 V10 HD 31313 (Network of Pediatric Pharmacology Research Units, to J.L.B.) from the National Institute of Child Health and Human Development, Bethesda, MD.

  • Abbreviations:
    COMT
    catechol-O-methyltransferase
    MAO
    monoamine oxidase
    DOPAL
    3,4-dihydroxyphenylacetaldehyde
    3-MT
    3-methoxytyramine
    HPLC
    high-performance liquid chromatography
    EC
    electrochemical detection
    3-O-MD
    3-O-methyldobutamine
    SAM
    S-adenosylmethionine
    S-COMT
    soluble catechol-O-methyltransferase
    M-COMT
    membrane-bound catechol-O-methyltransferase
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 301 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 301, Issue 1
1 Apr 2002
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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Kinetic Interactions of Dopamine and Dobutamine with Human Catechol-O-methyltransferase and Monoamine Oxidase in Vitro

Maohe Yan, Leslie T. Webster and Jeffrey L. Blumer
Journal of Pharmacology and Experimental Therapeutics April 1, 2002, 301 (1) 315-321; DOI: https://doi.org/10.1124/jpet.301.1.315

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Research ArticleABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Kinetic Interactions of Dopamine and Dobutamine with Human Catechol-O-methyltransferase and Monoamine Oxidase in Vitro

Maohe Yan, Leslie T. Webster and Jeffrey L. Blumer
Journal of Pharmacology and Experimental Therapeutics April 1, 2002, 301 (1) 315-321; DOI: https://doi.org/10.1124/jpet.301.1.315
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