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. 1969 Nov;37(3):638–649. doi: 10.1111/j.1476-5381.1969.tb08502.x

The role of Uptake2 in the extraneuronal metabolism of catecholamines in the isolated rat heart

S L Lightman, L L Iversen
PMCID: PMC1703732  PMID: 5348467

Abstract

1. (±)-3H-NA and labelled metabolites of NA were estimated in rat hearts after perfusion with various concentrations of NA in the range 0·01-50·0 μg/ml. Labelled metabolites of NA accounted for only a small proportion of the total uptake of radioactivity at low perfusion concentrations, but accounted for 50% of the total uptake at 1 μg NA/ml., thereafter declining to progressively smaller proportions at higher perfusion concentrations.

2. If the formation of labelled metabolites of 3H-NA was blocked by a combination of monoamine oxidase and catechol-O-methyl transferase inhibitors, the accumulation of unchanged 3H-NA was doubled when hearts were perfused with 1 μg NA/ml.

3. In hearts perfused with 0·5 μg NA/ml., an accumulation of unchanged 3H-NA was demonstrated in the presence of a combination of metabolic inhibitors and metaraminol. This appeared to be due to Uptake2, since the accumulation of NA under these conditions could be prevented by a low concentration of normetanephrine.

4. Phenoxybenzamine prevented extraneuronal uptake (Uptake2) and metabolism of 3H-NA with an estimated ID50 of 2·5 μM. The inhibition of Uptake2 by phenoxybenzamine (2·0 μM) was diminished at very high NA concentrations, suggesting that the drug may act competitively with NA.

5. It was concluded that Uptake2 operates at all catecholamine concentrations in the rat heart, but that in the lower range (less than 2·5 μg/ml. for NA and less than 0·75 μg/ml. for adrenaline) any catecholamine taken up by this process is rapidly metabolized. Thus the accumulation of unchanged amine is seen only at high perfusion concentrations.

6. The relevance of these results to an understanding of the possible physiological and pharmacological importance of Uptake2 is discussed.

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Selected References

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