Active uptake of MPP+, a metabolite of MPTP, by brain synaptosomes

Biochem Biophys Res Commun. 1985 May 16;128(3):1228-32. doi: 10.1016/0006-291x(85)91071-x.

Abstract

Mouse brain synaptosomal preparations were used to study uptake of N-methyl-4-phenylpyridine (MPP+), a metabolite of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). The uptake of [3H]-MPP+ by striatal synaptosomes was approximately 25 X greater than that of [3H]-MPTP, with a KM of 0.48 microM and a Vmax of 5.3 nmoles/g tissue/min. Uptake was Na+ dependent and inhibited by ouabain, cocaine and dopamine (Ki 0.12 microM). Synaptosomes prepared from the corpus striatum accumulated [3H]-MPP+ at a rate 5-10 times higher than preparations from other brain regions. This selective uptake of MPP+ may contribute to the specificity of the toxic effects of MPTP on nigrostriatal dopaminergic neurons.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium
  • Animals
  • Biological Transport, Active
  • Brain / metabolism*
  • Dopamine / metabolism
  • In Vitro Techniques
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism
  • Pyridines / metabolism*
  • Pyridinium Compounds / metabolism*
  • Synaptosomes / metabolism*

Substances

  • Pyridines
  • Pyridinium Compounds
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium
  • Dopamine