Effect of N-Methyl-4-Phenylpyridinium Ion on Monoamine Oxidase in a Clonal Rat Pheochromocytoma Cell Line, PC 12h

The effects of the neurotoxin N-methyl-4-phenylpyridinium ion (MPP+) on the enzymes involved in synthesis and catabolism of catecholamines were examined using a clonal rat pheochromocytoma cell line, PC12h, as a model of dopaminergic neurons. MPP+ added in the culture medium was found to be accumulated in PC12h cells after 30-min incubation. Monoamine oxidase (MAO) activity in PC12h cells was inhibited by MPP+ in a dose-dependent way from 10 nM to 10 microM, but concentrations of MPP+ higher than 100 microM were found to increase the MAO activity. At the lower concentrations MPP+ inhibited MAO noncompetitively with respect to the substrate, kynuramine, and at the higher concentrations it increased both the Km and the Vmax values of MAO toward the substrate. On the other hand, tyrosine hydroxylase activity and the dopamine concentrations in PC12 cells were not changed by incubation with MPP+ for 30 min, 60 min, or 24 h.