Uptake of 3H-catecholamines by rat liver cells occurs mainly through a system which is distinct from uptake1 or uptake2

Abstract

Isolated rat hepatocytes were incubated with 200 nmol/l 3H-(-)-noradrenaline or 50 nmol/l 3H-(-)-adrenaline for 15 min, in Krebs-Henseleit solution at 37 degrees C, gassed with 95% O2 5% CO2. Monoamine oxidase and catechol-O-methyl transferase were inhibited with pargyline (500 mumol/l) and Ro 01-2812 (3,5-dinitropyrocatechol; 2 mumol/l), respectively. Total radioactivity present in the cells, which corresponded mostly to intact 3H-amine, was measured. The content of 3H-noradrenaline increased with time of incubation, a plateau having been reached after 15 min of incubation. After 15 min of incubation, the cell: medium ratio for 3H-noradrenaline and 3H-adrenaline was 0.6-0.7. Desipramine (an inhibitor of the neuronal uptake of catecholamines-uptake1; 1 mumol/l) did not affect the uptake of either 3H-noradrenaline or 3H-adrenaline into hepatocytes. Corticosterone (an inhibitor of the extraneuronal uptake of catecholamines-uptake2; 40 mumol/l) slightly inhibited (by 28%) the uptake of 3H-adrenaline, and did not significantly reduce 3H-noradrenaline uptake. Probenecid (an inhibitor of the renal transport of organic anions; 100 mumol/l) did not influence the amount of either 3H-noradrenaline or 3H-adrenaline in hepatocytes. Cyanine 863 (an inhibitor of the renal transport of organic cations; 10 mumol/l) decreased by 62% the uptake of 3H-adrenaline into cells but did not significantly affect 3H-noradrenaline uptake. Bilirubin (a substrate of a hepatic transport for organic anions; 200 mumol/l) produced a significant increase (50%) in the amount of 3H-noradrenaline and 3H-adrenaline present in the cells.(ABSTRACT TRUNCATED AT 250 WORDS)