Ascorbic acid and striatal transport of [3H] 1-methyl-4-phenylpyridine (MPP+) and [3H] dopamine

Life Sci. 1988;42(25):2553-9. doi: 10.1016/0024-3205(88)90323-2.

Abstract

The inhibition of uptake of [3H] dopamine and [3H] 1-methyl-4-phenylpyridine (MPP+) was examined in mouse striatal synaptosomal preparations. Kinetic analysis indicated that ascorbic acid is a noncompetitive inhibitor of [3H] MPP+ uptake. No inhibition of [3H] dopamine uptake is observed. The dopamine uptake blockers, GBR-12909, cocaine, and mazindol strongly inhibit (IC50 less than 1 uM) both [3H] dopamine and [3H] MPP+ transport. Nicotine, its metabolites, and other tobacco alkaloids are weak inhibitors (IC50 greater than 1 mM) except 4-phenylpyridine and lobeline, which are moderate inhibitors (IC50 = 3 to 40 uM) of both [3H] dopamine and [3H] MPP+ uptake. These similarities in potencies are in agreement with the suggestion that [3H] MPP+ and [3H] dopamine are transported by the same carrier. The differences observed in the alteration of dopaminergic transport and mazindol binding by ascorbic acid suggest that ascorbic acid's effects on [3H] MPP+ transport are related to translocation and/or dissociation processes occurring subsequent to the initial binding event.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Ascorbic Acid / pharmacology*
  • Biological Transport
  • Cocaine / pharmacology
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Kinetics
  • Mazindol / pharmacology
  • Mice
  • Nicotine / pharmacology
  • Piperazines / pharmacology
  • Pyridines / metabolism*
  • Synaptosomes / metabolism

Substances

  • Piperazines
  • Pyridines
  • Nicotine
  • vanoxerine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Mazindol
  • Cocaine
  • Ascorbic Acid
  • Dopamine