Uptake of 1-methyl-4-phenylpyridinium and dopamine in the mouse brain cell nuclei.

The neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes, via its metabolite 1-methyl-4-phenylpyridinium (MPP+), parkinsonism in humans, monkeys, and mice but not in rats. When incubated with mouse brain homogenates, [3H]-MPP+ is recovered in relatively large concentrations in the brain cell nucleus. Although isolated cell nuclei from rat and mouse brain contain uptake systems for dopamine (DA), only brain cell nuclei from mice avidly take up [3H]MPP+. This nuclear uptake is ATP dependent and can be blocked by ouabain and N-ethylmaleimide. It is not, however, affected by neuronal and vesicular blockers such as benztropine, mazindol, and reserpine. Selective uptake of MPP+ into brain cell nuclei may provide a new avenue for future investigation into the complex modes of action of the neurotoxin MPTP.