UPTAKE AND METABOLISM OF H-3 ADRENALINE AND H-3 NORADRENALINE BY ISOLATED HEPATOCYTES AND LIVER SLICES OF THE RAT

• Type: Article in International Scientific Journal
• Date: 1993

Authors

Martel, F (Author) Other; AZEVEDO, I (Author) Other; OSSWALD, W (Author) Other

Journal

Title: Naunyn-Schmiedeberg's Archives of Pharmacology

Vol. 348

Pages: 450-457

ISSN: 0028-1298

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 6 Citations

Scopus - 13 Citations

Other information

Authenticus ID: P-001-MHD

DOI: 10.1007/bf00173202

Abstract (EN): Isolated rat hepatocytes were incubated with 0.05 mumol/l or 0.2 mumol/l H-3-(-)-noradrenaline or 0.05 mumol/l H-3-(-)-adrenaline for 15 min and the content of amines as well as the formation of metabolites was measured. The removal of both amines from the incubation medium was quantitatively similar, and mainly due to metabolism (which represented 96% of the removal of H-3-adrenaline and 98% of the removal of H-3-noradrenaline). O-methylation predominated for H-3-adrenaline: O-methylated and deaminated metabolites (H-3-OMDA) and H-3-metanephrine (H-3-MN) were the most abundant metabolites, accounting for 63% and 34% of total metabolite formation, respectively. Deamination predominated for H-3-noradrenaline: H-3-OMDA and H-3-dihydroxymandelic acid (H-3-DOMA) were the most abundant metabolites, representing respectively 56% and 36% of total metabolite formation. The following activities of monoamine oxidase and catechol-O-methyl transferase were determined for H-3-noradrenaline: k(COMT) 0.70 +/- 0.15 min-1 and k(MAO) 2.27 +/- 0.14 min-1. In experiments with H-3-noradrenaline, inhibition of monoamine oxidase reduced the formation of H-3-OMDA and deaminated metabolites [H-3]-dihydroxyphenylglycol (H-3-DOPEG) and H-3-DOMA] and increased the formation of H-3-normetanephrine (H-3-NMN). Inhibition of catechol-O-methyl transferase, on the other hand, decreased H-3-NMN and increased H-3-DOPEG formation. When both enzymes were inhibited, the formation of all metabolites was strongly reduced but surprisingly there was no accumulation of H-3-amines in the cells, as the cell: medium ratio for H-3-noradrenaline or H-3-adrenaline was about unity. In experiments with either H-3-noradrenaline or H-3-adrenaline, specific inhibitors of either uptake1 or uptake2 produced discrete effects, slightly decreasing the formation of H-3-OMDA and H-3-NMN or H-3-MN, and having no effect on H-3-amine content of the cells. Additional experiments were carried out with mt liver slices incubated for 15 min with H-3-noradrenaline 0.2 mumol/l. The pattern of metabolism of H-3-noradrenaline (H-3-OMDA and H-3-DOMA were the most abundant metabolites) as well as the degree of metabolism of the amine removed from the incubation medium (91% of the removal) were similar to those of the isolated cells. Likewise, there was no accumulation of intact H-3-noradrenaline in the tissue. Moreover, the results obtained with enzyme inhibitors as wells as with uptake inhibitors were similar to those obtained with hepatocytes. In conclusion, isolated hepatocytes remove and metabolize catecholamines very efficiently, being one of the most active systems studied in this respect. Uptake1 and uptake2 are responsible for part of the removal of catecholamines by hepatocytes; the system(s) involved in the remaining removal seem(s) to be active, but possess(es) characteristics that do not allow us to characterize it (them) either as uptake, or uptake2.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8