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.