Human neuroblastoma cell lines as models of catechol uptake.
This report compares the effect of antidepressants on the accumulation of [3H]catecholamines in two human neuroblastoma cell lines, IMR-32 and SK-N-SH, and a rat pheochromocytoma cell line, PC-12. Analysis of the catecholamine uptake system in SK-N-SH cells revealed that both [3H]dopamine and [3H]norepinephrine accumulated via a single competitive, saturable and apparently active process. Similar potencies exhibited by several inhibitors suggest that identical uptake systems exist in all 3 cell lines, with SK-N-SH cells being the most active. Although SK-N-SH and PC-12 cells have been reported to secrete dopamine in preference to other catecholamines, high intracellular concentrations of [3H]norepinephrine were measurable after incubation with [3H]dopamine. Additionally, [3H]norepinephrine/[3H]dopamine ratios increased with longer tracer incubations, in the presence of exogenous ascorbate and when including O-methylated metabolites. Moreover, accumulation of [3H]catechols was competitively inhibited by various antidepressants, with maximal inhibition to 7% of control and Kis consistent with reported noradrenergic uptake transport systems. Hence, the human neuroblastoma cell lines studied appear to serve as appropriate models of catechol reuptake processes in noradrenergic cells.
D000818:Animals; D002395:Catecholamines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009447:Neuroblastoma / Q000378:metabolism*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D010673:Pheochromocytoma / Q000378:metabolism; D051381:Rats
D002395:Catecholamines; D018492:Dopamine Antagonists; D004298:Dopamine; D009638:Norepinephrine