UPTAKE OF 1-METHYL-4-PHENYLPYRIDINIUM AND DOPAMINE IN THE MOUSE-BRAINCELL-NUCLEI

The neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) cau ses, via its metabolite 1-methyl-4-phenylpyridinium (MPP+), parkinsoni sm in humans, monkeys, and mice but not in rats. When incubated with m ouse brain homogenates, [H-3]-MPP+ is recovered in relatively large co ncentrations in the brain cell nucleus. Although isolated cell nuclei from rat and mouse brain contain uptake systems for dopamine (DA), onl y brain cell nuclei from mice avidly take up [H-3]MPP+. This nuclear u ptake is ATP dependent and can be blocked by ouabain and N-ethylmaleim ide. It is not, however, affected by neuronal and vesicular blockers s uch as benztropine, mazindol, and reserpine. Selective uptake of MPPinto brain Gell nuclei may provide a new avenue for future investigati on into the complex modes of action of the neurotoxin MPTP.