ISSN:
1432-1912
Keywords:
Adrenaline
;
Noradrenaline
;
Uptake1
;
Uptake2
;
Hepatocyte
;
Liver slice
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Isolated rat hepatocytes were incubated with 0.05 μmol/l or 0.2 μmol/l 3H-(−)-noradrenaline or 0.05 μmol/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-noradrenaline). 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-dihydroxyphenylglycol (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. In experiments with either 3H-noradrenaline or 3H-adrenaline, specific inhibitors of either uptake, or uptake2 produced discrete effects, slightly decreasing the formation of 3H-OMDA and 3H-NMN or 3H-MN, and having no effect on 3H-amine content of the cells. Additional experiments were carried Out with rat liver slices incubated for 15 min with 3H-noradrenaline 0.2 μmol/l. The pattern of metabolism of 3H-noradrenaline (3H-OMDA and 3H-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 3H-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 uptake1 or uptake2.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00173202
