Serotonergic conversion of MPTP and dopaminergic accumulation of MPP+

FEBS Lett. 1985 Sep 23;189(2):225-30. doi: 10.1016/0014-5793(85)81028-0.

Abstract

[3H]MPP+ had lower Km and higher Vmax values for its accumulation in rat brain synaptosomes than did [3H]MPTP. The kinetic parameters favored the uptake of [3H]MPP+ in the striatum to that in hypothalamus, whereas they were equally favorable for the uptake of [3H]MPTP in both regions. Hypothalamic uptake of [3H]MPTP and [3H]MPP+ was inhibited by desipramine, imipramine, norepinephrine, and serotonin. Striatal uptake of [3H]MPP+ and [3H]MPTP was blocked by nomifensine and dopamine. These results support the concept that MPTP accumulates in serotonergic neurons where it is oxidized by monoamine oxidase B to MPP+, which is released and then is selectively accumulated in dopaminergic neurons via the dopamine uptake system.

Publication types

  • Research Support, Non-U.S. Gov't
  • 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
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Hypothalamus
  • Kinetics
  • Norepinephrine / metabolism
  • Pyridines / metabolism*
  • Pyridinium Compounds / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Serotonin / metabolism*
  • Synaptosomes / metabolism

Substances

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