Effect of 1-methyl-4-phenylpyridinium (MPP+) on mitochondrial membrane potential in cerebellar neurons: interaction with the NMDA receptor
Effect of 1-methyl-4-phenylpyridinium (MPP+) on mitochondrial membrane potential in cerebellar neurons: interaction with the NMDA receptor
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DOI:
10.1007/bf01291876
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发表时间:
1997-01-01
影响因子:
3.3
通讯作者:
Camarasa, J
中科院分区:
文献类型:
--
作者:
Camins, A;Sureda, FX;Camarasa, J
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 mu M) and D-AP5 (IC50 value of 8.29 +/- 0.63 mu M), 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 A(2).