Summary
The handling of five amines by the extraneuronal deaminating system was studied in perfused hearts of rats (pretreated with reserpine; COMT and neuronal uptake inhibited). Hearts were perfused with 50 nmol/l 3H-noradrenaline for 30 min, in the presence of increasing concentrations of unlabelled (−)-adrenaline, (−)-noradrenaline, dopamine, tyramine and 5-HT. IC50's were determined as those concentrations of unlabelled amines which halved the steady-state rate of deamination of 3H-noradrenaline. After correction for changes in the tissue/medium ratio for 3H-noradrenaline, “half-saturating outside concentrations” were obtained. They increased in the order (−)-adrenaline (15 μmol/l) — tyramine — dopamine — noradrenaline —5-HT (53 μmol/l). The V max for extraneuronal deamination was determined for 3H-(−)-adrenaline, 3H-(−)-noradrenaline and 3H-dopamine, as well as (by HPLC and electrochemical detection) for tyramine and 5-HT. It was low for (−)-adrenaline, intermediate for (−)-noradrenaline, dopamine and 5-HT, high for tyramine. For the three catecholamines the half-saturating outside concentrations of the extraneuronal deaminating system clearly exceeded those for the extraneuronal O-methylating system of the same organ (see Grohmann and Trendelenburg 1985), although the two enzymes appear to co-exist in the same cells, so that the same transport system is involved.
Similar content being viewed by others
Abbreviations
- COMT:
-
catechol-O-methyl transferase
- DOMA:
-
dihydroxymandelic acid
- DOPEG:
-
dihydroxyphenylglycol
- 5-HT:
-
5-hydroxytryptamine
- MAO:
-
monoamine oxidase
References
Bönisch H (1980) The rate constants for the efflux of deaminated metabolites of 3H-dopamine from the perfused rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 314:231–235
Documenta Geigy (1969) Wissenschaftliche Tabellen, 7th edn. JR Geigy AG, Pharma, Basel
Fiebig ER, Trendelenburg U (1978a) The neuronal and extraneuronal uptake and metabolism of 3H-(−)-noradrenaline in the perfused rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 303:21–35
Fiebig ER, Trendelenburg U (1978b) The kinetic constants for the extraneuronal uptake and metabolism of 3H-(−)-noradrenaline in the perfused rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 303:37–45
Fowler CJ, Callingham BA, Mantle TJ, Tipton KF (1978) Monoamine oxidase A and B: a useful concept? Biochem Pharmacol 27:97–101
Gillespie JS, Preuner J (1976) Influence of iproniazid and 3′,4′-dihydroxy-2-methyl-propiophenone (U-0521) on uptake and metabolism of norepinephrine by rabbit colon. Naunyn-Schmiedeberg's Arch Pharmacol 293:R3
Grohmann M (1987) The activity of the neuronal and extraneuronal catecholamine-metabolizing enzymes of the perfused rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 336:139–147
Grohmann M, Trendelenburg U (1984) The substrate specificity of uptake2 in the rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 328:164–173
Grohmann M, Trendelenburg U (1985) The handling of five catecholamines by the extraneuronal O-methylating system of the rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 329: 264–270
Iversen LL (1965) The uptake of catechol amines at high perfusion concentrations in the rat isolated heart: A novel catechol amine uptake process. Brit J Pharmacol 25:18–33
Snedecor GW, Cochran WG (1980) Statistical methods, 7th edn. Iowa State University Press, Ames, USA
Trendelenburg U (1984a) The influence of inhibition of catechol-O-methyl transferase or of monoamine oxidase on the extraneuronal metabolism of 3H-(−)-noradrenaline in the rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 327:285–292
Trendelenburg U (1984b) Metabolizing systems. In: Fleming WW, Graefe KH, Weiner N (eds) Neuronal and extraneuronal events in autonomic pharmacology. Raven Press, New York, pp 93–109
Author information
Authors and Affiliations
Additional information
Supported by the Deutsche Forschungsgemeinschaft (SFB 176)
Send offprint requests to U. Trendelenburg
Rights and permissions
About this article
Cite this article
Grohmann, M., Trendelenburg, U. The handling of five amines by the extraneuronal deaminating system of the rat heart. Naunyn-Schmiedeberg's Arch Pharmacol 337, 159–163 (1988). https://doi.org/10.1007/BF00169243
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169243