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The activity of the neuronal and extraneuronal catecholamine-metabolizing enzymes of the perfused rat heart

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Summary

In a comparative study the neuronal and extraneuronal metabolism of several 3H-catecholamines (all of which were tritiated in the C-7 position of the side chain only) was determined in isolated rat hearts perfused at a concentration of the 3H-amines of 50 nmol/1. While the neuronal MAO activity was determined after inhibition of extraneuronal uptake (100 μmol/1 OMI) and COMT (10 μmol/1 U-0521), the extraneuronal MAO activity was estimated after inhibition of neuronal uptake (30 μmol/1 cocaine) and COMT. The extraneuronal COMT activity was determined under conditions of inhibition of both neuronal uptake and MAO (pretreatment with pargyline). Hearts were perfused with the 3H-catecholamines until the rate of appearance of the various 3H-metabolites in the venous effluent has reached a steady state. From these rates (v st-st) and the steady-state content of the unchanged 3H-catecholamines in the tissue (S i), the rate constants (V max/K m) for the unsaturated intracellular enzymes COMT (κCOMT) and MAO (κMAO) were calculated. The κCOMTvalues for all four catecholamines, (−)-noradrenaline, dopamine, (−)-adrenaline and (±)-isoprenaline exhibit a range from 0.24 to 0.78 min−1; the metabolism of the catecholamines by the COMT differs: (-)-noradrenaline = dopamine < (−)-adrenaline < (±)-isoprenaline. The extraneuronal MAO activity was low for all three catecholamines, (−)-adrenaline, (−)-noradrenaline and dopamine (range of κMAOfrom 0.05 to 0.28 min−1) and declined in the order: (−)-adrenaline < (−)-noradrenaline < dopamine. The neuronal MAO activity for (−)-adrenaline, (−)-noradrenaline and dopamine was slightly higher than that in the extraneuronal cells (range of kMAO from 0.08 to 0.35 min−1), but the ranking order showed the same pattern: (−)-adrenaline < (−)-noradrenaline = dopamine.

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Abbreviations

MAO:

monoamine oxidase

COMT:

catechol-Omethyltransferase

NMN:

normetanephrine

MN:

metanephrine

MT:

3-methoxytyramine

OMI:

3-O-methyl-isoprenaline

DOPEG:

dihydroxyphenylglycol

DOPET:

dihydroxyphenylethanol

DOMA:

dihydroxymandelic acid

DOPAC:

dihydroxyphenylacetic acid

U-0521:

3,4-dihydroxy-2-methyl propiophenone

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  1. Institut für Pharmakologie and Toxikologie der Universität Würzburg, Versbacher Straße 9, D-8700, Würzburg, Federal Republic of Germany

    M. Grohmann

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Grohmann, M. The activity of the neuronal and extraneuronal catecholamine-metabolizing enzymes of the perfused rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 336, 139–147 (1987). https://doi.org/10.1007/BF00165797

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  • DOI: https://doi.org/10.1007/BF00165797

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