Effect of 1-methyl-4-phenylpyridinium (MPP+) on mitochondrial membrane potential in cerebellar neurons: interaction with the NMDA receptor

J Neural Transm (Vienna). 1997;104(6-7):569-77. doi: 10.1007/BF01291876.

Abstract

The effect of MPP+, a dopaminergic neurotoxin, in mitochondrial membrane potential was investigated in dissociated cerebellar granule cells using rhodamine 123 and flow cytometry. MPP+ (1 mM) decreased the mitochondrial membrane potential by 30%. Antagonists of the NMDA receptor complex, such as MK-801 (IC50 value of 20.92 +/- 0.02 nM), 5,7-dichlorokynurenic acid (IC50 value of 6.46 +/- 1.06 microM) and D-AP5 (IC50 value of 8.29 +/- 0.63 microM), inhibited the action of MPP+. Neither NBQX, nor riluzole, nor desipramine modified the action of MPP+. Dibucaine restored the basal values of mitochondrial membrane potential altered by MPP+. Since, in the presence of NMDA, MPP+ antagonized the effect of this total agonist, it can be concluded that, in this preparation, MPP+ interacts with the NMDA receptor complex as a partial agonist. This interaction could be the result of an allosteric modulation of the NMDA receptor complex by MPP+. The decrease of mitochondrial membrane potential induced by MPP+ is antagonized by dibucaine, suggesting that this effect is mediated by an activation of phospholipase A2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / pharmacology*
  • Animals
  • Cerebellum / cytology
  • Cerebellum / drug effects*
  • Dopamine Agents / pharmacology*
  • Flow Cytometry
  • Intracellular Membranes / drug effects
  • Logistic Models
  • Membrane Potentials / drug effects
  • Mitochondria / drug effects*
  • Neurons / drug effects
  • Neurotoxins / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / drug effects*

Substances

  • Dopamine Agents
  • Neurotoxins
  • Receptors, N-Methyl-D-Aspartate
  • 1-Methyl-4-phenylpyridinium