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

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Summary

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 μM) and D-AP5 (IC50 value of 8.29 ± 0.63 μM), 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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Author notes

  1. J. Camarasa

    Present address: Unitat de Farmacologia i Farmacognosia, Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain

Authors and Affiliations

  1. Unitat de Farmacologia i Farmacognosia, Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain

    A. Camins, F. X. Sureda, C. Gabriel, M. Pallàs & E. Escubedo

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  1. A. Camins
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  2. F. X. Sureda
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  3. C. Gabriel
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  4. M. Pallàs
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  5. E. Escubedo
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  6. J. Camarasa
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Camins, A., Sureda, F.X., Gabriel, C. et al. Effect of 1-methyl-4-phenylpyridinium (MPP+) on mitochondrial membrane potential in cerebellar neurons: Interaction with the NMDA receptor. J. Neural Transmission 104, 569–577 (1997). https://doi.org/10.1007/BF01291876

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  • DOI: https://doi.org/10.1007/BF01291876

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