THE FATE OF [H-3] (-)-NORADRENALINE IN THE PERFUSED-RAT-LIVER

• Type: Article in International Scientific Journal
• Date: 1995

Authors

Martel, F (Author) FMUP; AZEVEDO, I (Author) Other

Journal

Title: Journal of Autonomic Pharmacology

Vol. 15

Pages: 309-319

ISSN: 0144-1795

Publisher: Blackwell

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 4 Citations

Other information

Authenticus ID: P-001-G7W

DOI: 10.1111/j.1474-8673.1995.tb00397.x

Abstract (EN): 1 Hepatic removal and metabolism as well as biliary excretion of noradrenaline were studied. Rat livers were perfused in situ for 60 min with Krebs-Henseleit buffer at 37 degrees C containing 2 nM [H-3]-(-)-noradrenaline. [H-3]-noradrenaline and its [H-3]-metabolites were determined in liver, venous effluent and bile. 2 Removal of [H-3]-noradrenaline by the liver, calculated as the sum of total radioactivity in the liver at the end of perfusion plus total radioactivity in the bile formed during perfusion plus [H-3]-metabolites in the venous effluent formed during perfusion, was 40.2 +/- 6.9 pmol g(-1) h(-1). This removal corresponded to about 25% of the amount of [H-3]-noradrenaline offered to the liver. 3 A proportion of the [H-3]-noradrenaline (86.8%) taken up by the Liver was metabolized, 13.2% remained unmetabolized in the liver and 0.019% was excreted unmetabolized into the bile. The most abundant metabolites were those present in the [H-3]-OMDA fraction (72.5%), followed by [H-3]-NMN (15.8%), [H-3]-DOPEG (6.1%) and [H-3]-DOMA (5.6%). Some of these metabolites (66.6%) were recovered from the venous effluent, 32.7% from the Liver and only 1.3% from the bile. The amount of [H-3]-noradrenaline present in the liver at the end of the perfusion produced a tissue:perfusion medium ratio of 2.6. 4 Simultaneous inhibition of monoamine oxidase and catechol-O-methyl transferase With pargyline (75 mg kg(-1), i.p., 3 h before) and tolcapone (1 mu M), respectively, markedly reduced the formation of [H-3]-NMN, [H-3]-DOPEG and [H-3]-DOMA, but did not affect the hepatic removal of [H-3]-noradrenaline, the content of [H-3]-noradrenaline in the liver, the formation of [H-3]-OMDA or the excretion of [H-3]-noradrenaline and its [H-3]-metabolites into the bile. 5 Treatment with an uptake(2) blocker, corticosterone (40 mu M), did not change the hepatic removal and metabolism of [H-3]-noradrenaline or the biliary excretion of [H-3]-noradrenaline and its [H-3]-metabolites. 6 These findings indicate that the perfused rat Liver efficiently removed and metabolized [H-3]-noradrenaline, both monoamine oxidase and catechol-O-methyl transferase being involved in the metabolism of this amine. The apparent lack of effect of monoamine oxidase and catechol-O-methyl transferase inhibition on the formation of [H-3]-OMDA may be due to the presence, especially in the liver, of conjugated metabolites of [H-3]-noradrenaline in the [H-3]-OMDA fraction. These results also show that uptake(2) does not seem to be involved in the hepatic uptake of [H-3]-noradrenaline, confirming previous findings. Finally, the results indicate that the rat Liver perfused with Krebs-Henseleit buffer is not a suitable experimental model for studies on the biliary excretion of catecholamines.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11