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

Journal of Neural Transmission
A CaminsJ Camarasa

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.

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Citations

Nov 13, 2001·Brain Research Bulletin·R A González-PoloJ M Fuentes
Dec 3, 2003·Journal of Physiology and Biochemistry·J JordánJ H M Prehn
Apr 5, 2003·Journal of Neurochemistry·Tiesong ShangCecilia J Hillard
Apr 13, 1999·Biochemical and Biophysical Research Communications·R M Chalmers-RedmanW G Tatton
Dec 22, 2017·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Catherine A OpereNajam A Sharif
Oct 1, 2014·PloS One·Linton WinderJohn M Holland
Sep 14, 2018·Frontiers in Molecular Neuroscience·Md JakariaDong-Kug Choi

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