1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolism and 1-methyl-4-phenylpyridinium uptake in dissociated cell cultures from the embryonic mesencephalon

摘要: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a contaminant found in synthetic illicit drug, can elicit humans and monkeys severe extrapyramidal syndrome similar to Parkinson's disease. It also induces alterations of the dopamine (DA) pathways rodents. MPTP neurotoxicity requires its enzymatic transformation into 1-methyl-4-phenylpyridinium (MPP+) by monoamine oxidase followed concentration target cells, DA neurons. Here, we show that mesencephalic glial cells from mouse embryo take up vitro, transform it MPP+, release culture medium. is not taken neurons either mesencephalon or striatum vitro (8 days serum-free conditions). However, revealed high-affinity uptake mechanism for metabolite DA. The affinity (Km) fivefold higher than MPP+ (0.2 1.1 microM, respectively), whereas number sites double (Vmax = 25 55 pmol/mg protein/min respectively). Mazindol, inhibitor, blocks equally well under these conditions. Moreover, competition experiments, two molecules appear use same carrier(s) enter Small concentrations are striatal vitro. amount represented less 10% Depolarization induced veratridine released comparable proportions labeled cultures.(ABSTRACT TRUNCATED AT 250 WORDS)