ISSN:
1435-1463
Keywords:
1-methyl-4-phenylpyridinium
;
NMDA antagonists
;
mitochondrial membrane potential
;
flow cytometry
;
rhodamine 123
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01291876
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