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The isotope effect of tritium in3H-noradrenaline

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Summary

In a variety of tissues of organs3H-(−)-7-,3H-(−)-7,8 and3H-(−)-2,5,6-noradrenaline were compared, partly also with unlabelled (−)-noradrenaline. The following isotope effects were found:

  1. 1.

    Neuronal uptake (vas deferens, rabbit heart): tritium reduced the neuronal uptake by a factor of 1.3 to 2.0 (reduction:3H-7-<3H-7,8-<3H-2,5,6-noradrenaline).

  2. 2.

    Extraneuronal uptake (rat heart): tritium reduced the extraneuronal uptake of noradrenaline by a factor of 1.3 to 1.8 (reduction:3H-7-<3H-7,8-<3H-2,5,6-noradrenaline).

  3. 3.

    Monoamine oxidase (MAO; homogenates of rat heart):3H-7-noradrenaline was a better substrate than was unlabelled noradrenaline, but3H-7,8- and3H-2,5,6-noradrenaline were inferior substrates.

  4. 4.

    Neuronal and extraneuronal deaminating systems: in the intact cells of the rat vas deferens (neuronal deaminating system) or of the rat heart exposed to cocaine (extraneuronal deaminating system) the low rate constant characterizing the deamination of3H-7,8- and3H-2,5,6-noradrenaline resulted in high intracellular concentrations of3H-noradrenaline; consequently, the low rate constant failed to greatly affect steady-state rates of deamination.

  5. 5.

    Catechol-O-methyl transferase (COMT): in rat heart homogenates the rate constant for the O-methylation of3H-noradrenaline was: unlabelled (−)-noradrenaline=3H-(−)-7-noradrenaline>3H-(−)-2,5,6-noradrenaline.

  6. 6.

    Extraneuronal O-methylating system (rat heart exposed to cocaine): steady-state rates of formation of3H-NMN were higher for3H-7- than for3H-7,8-noradrenaline, but an inverse relationship was found for the intracellular accumulation of labelled amine.

It is concluded that tritium has an isotope effect, the magnitude of which depends on its position in the noradrenaline molecule. However, except for the hindrance of dedamination by tritium in position 8, all isotope effects reported here were rather small.

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Abbreviations

MAO:

monoamine oxidase

COMT:

eatechol-O-methyl transferase

NMN:

normetanephrine

DOPEG:

dihydroxyphenylglycol

DOMA:

dihydroxymandelic acid

MOPEG:

methoxyhydroxyphenylglycol

VMA:

methoxyhydroxymandelic acid

OMDA:

sum of MOPEG+VMA

OM:

sum of NMN+MOPEG+VMA

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Authors and Affiliations

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

    U. Trendelenburg, F. J. E. Stefano & M. Grohmann

Authors
  1. U. Trendelenburg
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  2. F. J. E. Stefano
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  3. M. Grohmann
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Additional information

This study was supported by the Deutsche Forschungsgemeinschaft (Tr. 96)

On sabbatical leave, supported by the Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires

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Trendelenburg, U., Stefano, F.J.E. & Grohmann, M. The isotope effect of tritium in3H-noradrenaline. Naunyn-Schmiedeberg's Arch. Pharmacol. 323, 128–140 (1983). https://doi.org/10.1007/BF00634260

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  • DOI: https://doi.org/10.1007/BF00634260

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