Summary
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1.
Hearts were obtained from reserpine-pretreated rats and perfused with 0.95 μM 3H-(−)-noradrenaline. The rate of removal of 3H-noradrenaline from the perfusion fluid was measured (from the arterio-venous difference) as well as the rate at which the 3H-metabolites appeared in the venous effluent.
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2.
When either 30 μM cocaine or 87 μM corticosterone was added under steady-state conditions during perfusion with 3H-noradrenaline (to inhibit neuronal and extraneuronal uptake, respectively), each inhibitor reduced the removal of noradrenaline by about 50%; in the presence of both inhibitors removal was abolished.
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3.
Dihydroxymandelic acid (DOMA) was of neuronal, normetanephrine (NMN) of extraneuronal origin; dihydroxyphenylglycol (DOPEG) and the OMDA fraction (containing methoxyhydroxyphenylglycol-MOPEG-and methoxyhydroxymandelic acid-VMA) were formed both neuronally and extraneuronally.
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4.
The extraneuronal metabolism of 3H-noradrenaline was in quick equilibrium with the 3H-noradrenaline in the perfusion fluid; most of the total formation of DOPEG, MOPEG and NMN was recovered from the venous effluent.
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5.
Extraneuronally formed DOPEG, MOPEG and NMN distributed in the tissue with half times corresponding to their half time for efflux.
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6.
Inhibition of monoamine oxidase (MAO) by pargyline increased the extraneuronal formation of NMN; MAO and catechol-O-methyl transferase (COMT) appear to be contained in the same extraneuronal compartment.
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7.
The extraneuronal accumulation of 3H-noradrenaline required 30 min or more to reach a steady state; inhibition of one or both enzymes slowed this process. Inhibition of MAO increased the extraneuronal accumulation of 3H-noradrenaline; inhibition of COMT failed to do so, since the enzyme inhibitor (U-0521) was a weak inhibitor of extraneuronal uptake.
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8.
The rate constants for the efflux of the metabolites of noradrenaline decreased in the order of MOPEG>DOPEG>NMN>DOMA>VMA.
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This study was supported by the Deutsche Forschungsgemeinschaft
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Fiebig, E.R., Trendelenburg, U. The neuronal and extraneuronal uptake and metabolism of 3H-(−)-noradrenaline in the perfused rat heart. Naunyn-Schmiedeberg's Arch. Pharmacol. 303, 21–35 (1978). https://doi.org/10.1007/BF00496182
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DOI: https://doi.org/10.1007/BF00496182