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Extraneuronal uptake and O-methylation of 3H-adrenaline in the rabbit aorta

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Summary

The influence of uptake2 inhibitors on the Omethylation and accumulation of 3H-adrenaline by the isolated rabbit aorta was studied. Strips were incubated with 0.05 μmol/l 3H-(−)-adrenaline during 15 min. Monoamine oxidase and uptake, were inhibited and the 3H-adrenaline present in the tissue was measured as well as the metabolites found in the tissue and in the incubation fluid. In another series of experiments, monoamine oxidase, uptake1 and catechol-O-methyl transferase (COMT) were inhibited, and tritium accumulation was measured in the tissue.

When COMT was inhibited, inhibitors of uptake2 produced a maximal reduction of 3H-adrenaline accumulation that did not exceed 50%. When COMT was in tact, inhibitors of uptake2 diminished total 3H-removal and, more markedly, O-methylation and concomitantly increased the tissue content of 3H-adrenaline.

Mineralocorticoids (corticosterone and deoxycorticosterone acetate) inhibited 3H-adrenaline uptake (when COMT was inhibited) and 3H-metanephrine formation (when COMT was functional) as effectively as did sexual steroids (17-β-oestradiol, progesterone and testosterone); hydrocortisone (hemisuccinate or phosphate) had no effect (for concentrations up to 120 μmol/l).

At the end of the incubation some strips were washed out with amine-free solution. Compartmental analysis of the efflux showed that the amine had distributed into three extraneuronal compartments (compartment I, II and III, with half times of 0.4, 4 and 15 min, respectively). Corticosterone (120 μmol/l). decreased the amount of 3H-adrenaline in compartment III and simultaneously increased the amount of the amine in compartment I (extracellular space).

The extraneuronal accumulation of 3H-adrenaline in rabbit aorta can be only partially ascribed to uptake2, as already stated by other authors; our results clearly show that inhibition of uptake2 increases the amount of 3H-adrenaline in the extracellular space, i. e., uptake2 creates a concentration gradient for 3H-adrenaline in the extracellular space; elastin and collagen represent very probably the site of binding of 3H-adrenaline which is independent of uptake2.

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Abbreviations

COMT:

Catechol-O-methyltransferase

DOCA:

deoxycorticosterone acetate

DOMA:

3,4-dihydroxymandelic acid

DOPEG:

3,4-dihydroxyphenylglycol

MAO:

monoamine oxidase

OMDA:

O-methylated and deaminated metabolites

MOPEG:

methoxyhydroxyphenylglycol

VMA:

methoxyhydroxymandelic acid

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, Faculty of Medicine, P-4200, Porto, Portugal

    Fátima Martel, Isabel Azevedo & Walter Osswald

Authors
  1. Fátima Martel
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  2. Isabel Azevedo
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  3. Walter Osswald
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Additional information

A preliminary account of some of the results was presented to the 7th International Catecholamine Symposium in Amsterdam. Supported by Instituto Nacional de Investigação Cientffica (INIC, FmP1)

PhD student with a grant from JNICT (Programa Ciência)

Correspondence to F. Martel at the above address

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Martel, F., Azevedo, I. & Osswald, W. Extraneuronal uptake and O-methylation of 3H-adrenaline in the rabbit aorta. Naunyn-Schmiedeberg's Arch Pharmacol 347, 363–370 (1993). https://doi.org/10.1007/BF00165385

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  • DOI: https://doi.org/10.1007/BF00165385

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