Uptake and metabolism of 3H-adrenaline and 3H-noradrenaline by isolated hepatocytes and liver slices of the rat.
Isolated rat hepatocytes were incubated with 0.05 mumol/l or 0.2 mumol/l 3H-(-)-noradrenaline or 0.05 mumol/l 3H-(-)-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 3H-adrenaline and 98% of the removal of 3H-noradenaline). O-methylation predominated for 3H-adrenaline: O-methylated and deaminated metabolites (3H-OMDA) and 3H-metanephrine (3H-MN) were the most abundant metabolites, accounting for 63% and 34% of total metabolite formation, respectively. Deamination predominated for 3H-noradrenaline: 3H-OMDA and 3H-dihydroxymandelic acid (3H-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 3H-noradrenaline: kCOMT 0.70 +/- 0.15 min-1 and kMAO 2.27 +/- 0.14 min-1. In experiments with 3H-noradrenaline, inhibition of monoamine oxidase reduced the formation of 3H-OMDA and deaminated metabolites [3H-dihydroxphenylglycol (3H-DOPEG) and 3H-DOMA] and increased the formation of 3H-normetanephrine (3H-NMN). Inhibition of catechol-O-methyl transferase, on the other hand, decreased 3H-NMN and increased 3H-DOPEG formation. When both enzymes were inhibited, the formation of all metabolites was strongly reduced but surprisingly there was no accumulation of 3H-amines in the cells, as the cell: medium ratio for 3H-noradrenaline or 3H-adrenaline was about unity.(ABSTRACT TRUNCATED AT 250 WORDS)
Martel
F
F
Department of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
Azevedo
I
I
Osswald
W
W
D000818:Animals; D003080:Cold Temperature; D003891:Desipramine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D003891:Desipramine; D009638:Norepinephrine; D004837:Epinephrine