Summary
The influence of inhibitors of metabolism and uptake of noradrenaline on the 3H-noradrenaline removal from the perfusion fluid by the isolated rat liver was studied. Livers were perfused with 3 nmol/l 3H-noradrenaline and 3H-noradrenaline and 3H-metabolites were determined in effluent, liver and bile. After the perfusion with 14,900 ±920 dpm · g−1 · min−1 during 90 min, cumulative removal of tritium was 323,574 ± 63,103 dpm/g. 3H-metabolites recovered from the liver after 90 min perfusion represented 71.1 ± 9.0% of total metabolite formation. Only the OMDA-fraction appeared in the perfusate; its approach to steady state of efflux was slow. The inhibition either of MAO or COMT changed neither the total removal of tritium nor the 3H-metabolites recovered from the liver. Cocaine (10 μmol/l) reduced the accumulation of 3H-noradrenaline in the liver. The uptake2 inhibitor corticosterone (30 μmol/l) diminished total removal of tritium and the 3H-metabolites recovered from the liver without changing the accumulation of 3H-noradrenaline. The hypothesis of two different compartments, one responsible for the metabolism and the other for the accumulation of the amine is discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- NA:
-
noradrenaline
- NMN:
-
normetanephrine
- OMDA:
-
O-methylated deaminated metabolites
- MAO:
-
monoamine oxidase
- COMT:
-
catechol-O-methyl transferase
References
Axelrod J (1959) Metabolism of epinephrine and other sympathomimetic amines. Physiol Rev 39:751–776
Carlsson A, Waldeck B (1963) On the role of the liver catechol-O-methyl transferase in the metabolism of circulating catecholamines. Acta Pharmacol Toxicol 20:47–55
Da Prada M, Picotti GB, Carruba MO, Haefely WE (1979) Plasma catecholamine, normetanephrine and p-octopamine levels: stress- and drug-induced changes in rat. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines: Basic and clinical frontiers, vol 1. Pergamon Press, New York, pp 915–917
Fiebig ER, Trendelenburg U (1978) 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
Garceau D, Yamaguchi N (1982) Pharmacological evidence for the existence of a neuronal amine uptake mechanism in the log liver in vivo. Can J Physiol Pharmacol 60:755–762
Graefe KH, Stefano FJE, Langer SZ (1973) Preferential metabolism of (−)-3H-norepinephrine through the deaminated glycol in the rat vas deferens. Biochem Pharmacol 22:1147–1160
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
Houslay MD, Tipton KF (1974) A kinetic evaluatin of monoamine oxidase activity in rat liver mitochondrial outer membranes. Biochem J 139:645–652
Iversen LL (1967) The uptake and storage of noradrenaline in sympathetic nerves. Cambridge University Press, Cambridge
Jarrot B (1971) Occurrence and properties of catechol-O-methyl transferase in adrenergic neurons. J Neurochem 18:17–27
Krebs HA, Henseleit K (1932) Untersuchungen über die Harnstoffbildung im Tierkörper. Hoppe-Seyler's Z Physiol Chem 210:33–66
Lightman SL, Hems DA (1973) Metabolism of adrenaline in the isolated perfused liver of the rat. Biochem Pharmacol 22:2419–2423
McCaman RE, McCaman MW, Hunt JW, Smith SM (1965) Microdetermination of monoamine oxidase and 5-hydroxytryptophan decarboxilase in nervous tissue. J Neurochem 12:15–23
Ruckebush Y, Poupet M, Grivel ML, Berard P, Bousquet G (1968) Inactivation hépatique des catécholamines apres dérivation porto-hépatique sélective chez le chien. C R Soc Biol 162:930–937
Scholz R, Hansen W, Thurman R (1973) Interaction of mixed-function oxidation with biosynthetic processes. I. Inhibition of gluconeogenesis by aminopyrine in perfused rat liver. Eur J Biochem 38:64–72
Tarizzo V, Rubio MC (1982) Pharmacological effects of ionophore A-23187 on isolated guinea-pig atria and isolated cat nictitating membrane. Gen Pharmacol 13:111–116
Tipton KF (1973) Biochemical aspects of monoamine oxidase. Br Med Bull 29:116–119
Trendelenburg U (1984) Metabolizing systems. In: Fleming WW, Langer SZ, Graefe KH, Weiner N (eds) Neuronal and extraneuronal events in autonomic pharmacology. Raven Press, New York, pp 93–109
Vane JR (1969) The release and fate of vasoactive hormone in the circulation. Br J Pharmacol 35:209–242
Yamaguchi N, Garceau D (1980) Correlation between hemodynamic parameters of the liver and norepinephrine release upon hepatic nerve stimulation in the dog. Can J Physiol Pharmacol 58:1347–1355
Author information
Authors and Affiliations
Additional information
Send offprint requests to M. C. Rubio
Rights and permissions
About this article
Cite this article
Steinberg, P., Acevedo, C., Masana, M.I. et al. Uptake and metabolism of 3H-(±)-noradrenaline in the isolated perfused rat liver. Naunyn-Schmiedeberg's Arch Pharmacol 337, 392–396 (1988). https://doi.org/10.1007/BF00169529
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169529