Selective MPP+ uptake into synaptic dopamine vesicles: possible involvement in MPTP neurotoxicity

Br J Pharmacol. 1993 Jun;109(2):411-4. doi: 10.1111/j.1476-5381.1993.tb13584.x.

Abstract

1. In the present study we provide evidence for a saturable, Mg2+/ATP- and temperature-dependent, tetrabenazine-, dopamine-, and amphetamine-sensitive uptake of 1-methyl-4-phenylpyridinium ion (MPP+) in synaptic vesicles from mouse striatum. 2. Similarity in the properties of the vesicular uptake suggests that in the striatum dopamine and MPP+ share the vesicular carrier. 3. The presence of MPP+ vesicular uptake in dopamine-rich regions such as striatum, olfactory, tubercles and hypothalamus, as well as its absence in cerebellum, cortex and pons-medulla, suggest that monoamine vesicular carriers differ between highly and poorly dopamine-innervated regions. 4. The restriction of active MPP+ uptake to the dopaminergic regions, which reflects the previously shown distribution of [3H]-MPP+ binding sites in mouse brain membranes, indicates MPP+ as a marker of the vesicular carrier for dopamine in dopaminergic neurones. 5. A role in MPP+ neurotoxicity is suggested for this region-specific, vesicular storage of the toxin.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / analogs & derivatives*
  • Amphetamine / pharmacology
  • Animals
  • Biomarkers
  • Brain / drug effects
  • Brain / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine / pharmacology
  • Dopamine / physiology*
  • Dopamine Agents / toxicity*
  • In Vitro Techniques
  • MPTP Poisoning
  • Male
  • Mice
  • Microscopy, Electron
  • Nervous System Diseases / chemically induced*
  • Nervous System Diseases / metabolism
  • Pyridinium Compounds / metabolism*
  • Synaptic Vesicles / metabolism*
  • Tetrabenazine / pharmacology

Substances

  • Biomarkers
  • Dopamine Agents
  • Pyridinium Compounds
  • 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine
  • 1-(4-methoxyphenyl)pyridinium
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Amphetamine
  • Dopamine
  • Tetrabenazine