| The fate of [3H]-(-)-noradrenaline in the perfused rat liver. | |
| | |
MedLine Citation:
|
PMID: 8744971 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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 [3H]-(-)-noradrenaline. [3H]-noradrenaline and its [3H]-metabolites were determined in liver, venous effluent and bile. 2. Removal of [3H]-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 [3H]-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 [3H]-noradrenaline offered to the liver. 3. A proportion of the [3H]-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 [3H]-OMDA fraction (72.5%), followed by [3H]-NMN (15.8%), [3H]-DOPEG (6.1%) and [3H]-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 [3H]-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 microM), respectively, markedly reduced the formation of [3H]-NMN, [3H]-DOPEG and [3H]-DOMA, but did not affect the hepatic removal of [3H]-noradrenaline, the content of [3H]-noradrenaline in the liver, the formation of [3H]-OMDA or the excretion of [3H]-noradrenaline and its [3H]-metabolites into the bile. 5. Treatment with an uptake2 blocker, corticosterone (40 microM), did not change the hepatic removal and metabolism of [3H]-noradrenaline or the biliary excretion of [3H]-noradrenaline and its [3H]-metabolites. 6. These findings indicate that the perfused rat liver efficiently removed and metabolized [3H]-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 [3H]-OMDA may be due to the presence, especially in the liver, of conjugated metabolites of [3H]-noradrenaline in the [3H]-OMDA fraction. These results also show that uptake2 does not seem to be involved in the hepatic uptake of [3H]-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. |
| | |
Authors:
|
F Martel; I Azevedo |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Journal of autonomic pharmacology Volume: 15 ISSN: 0144-1795 ISO Abbreviation: J Auton Pharmacol Publication Date: 1995 Oct |
Date Detail:
|
Created Date: 1996-10-16 Completed Date: 1996-10-16 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 8106455 Medline TA: J Auton Pharmacol Country: ENGLAND |
Other Details:
|
Languages: eng Pagination: 309-19 Citation Subset: IM |
Affiliation:
|
Faculty of Medicine, Institute of Pharmacology and Therapeutics, Porto, Portugal. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adrenergic Uptake Inhibitors
/
pharmacology Animals Benzophenones / pharmacology Catechol O-Methyltransferase / antagonists & inhibitors Corticosterone / pharmacology Liver / metabolism* Male Monoamine Oxidase Inhibitors / pharmacology Nitrophenols Norepinephrine / metabolism* Pargyline / pharmacology Rats Rats, Wistar Tritium |
| Chemical | |
Reg. No./Substance:
|
0/Adrenergic Uptake Inhibitors; 0/Benzophenones; 0/Monoamine Oxidase Inhibitors; 0/Nitrophenols; 10028-17-8/Tritium; 134308-13-7/tolcapone; 50-22-6/Corticosterone; 51-41-2/Norepinephrine; 555-57-7/Pargyline; EC 2.1.1.6/Catechol O-Methyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Sequential effects in lexical decision: tests of compound-cue retrieval theory.
Next Document: Age-related changes in contractile responses to noradrenaline in isolated blood vessels from rat and...