Abstract (EN):
Isolated rat hepatocytes were incubated with 200 nmol/l H-3-(-)-noradrenaline or 50 nmol/l H-3-(-)-adrenaline for 15 min, in Krebs-Henseleit solution at 37 degrees C, gassed with 95% O-2 5% CO2. Monoamine oxidase and catechol-O-methyl transferase were inhibited with pargyline (500 mu mol/l) and Ro 01-2812 (3,5-dinitropyrocatechol; 2 mu mol/l), respectively. Total radioactivity present in the cells, which corresponded mostly to intact H-3-amine, was measured. The content of H-3-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 H-3-noradrenaline and H-3-adrenaline was 0.6 - 0.7. Desipramine (an inhibitor of the neuronal uptake of catecholamines - uptake(1); 1 mu mol/l) did not affect the uptake of either H-3-noradrenaline or H-3-adrenaline into hepatocytes. Corticosterone (an inhibitor of the extraneuronal uptake of catecholamines - uptake(2); 40 mu mol/l) slightly inhibited (by 28%) the uptake of H-3-adrenaline, and did not significantly reduce H-3-noradrenaline uptake. Probenecid (an inhibitor of the renal transport of organic anions; 100 mu mol/l) did not influence the amount of either H-3-noradrenaline or H-3-adrenaline in hepatocytes. Cyanine 863 (an inhibitor of the renal transport of organic cations; 10 mu mol/l) decreased by 62% the uptake of H-3-adrenaline into cells but did not significantly affect H-3-noradrenaline uptake. Bilirubin (a substrate of a hepatic transport for organic anions; 200 mu mol/l) produced a significant increase (50%) in the amount of H-3-noradrenaline and H-3-adrenaline present in the cells. When isolated hepatocytes were incubated in a sodium-free medium (sodium being replaced by choline or lithium) there was a very marked inhibition of H-3-noradrenaline and H-3-adrenaline uptake (by 85-97%). An increase in potassium content of the medium (from 6.6 to 50 mmol/l) did not affect the uptake of either H-3-amine into isolated cells. In conclusion, the uptake of catecholamines by isolated liver cells possesses characteristics that distinguish it from the classic uptake systems for catecholamines (uptake, and uptake(2)): (1) it is sodium-dependent but not affected by desipramine; (2) it is only slightly sensitive to corticosterone and not affected by potassium-induced depolarization; (3) it is partially sensitive to cyanine 863. Moreover, the increase of H-3-amine content in the cells in the presence of bilirubin suggests the possibility of catecholamines being excreted from the hepatocytes through the bilirubin transporter.
Language:
English
Type (Professor's evaluation):
Scientific
No. of pages:
6