EFFECT OF 1-METHYL-4-PHENYLPYRIDINIUM (MPP-MEMBRANE POTENTIAL IN CEREBELLAR NEURONS - INTERACTION WITH THE NMDA RECEPTOR() ON MITOCHONDRIAL)

The effect of MPP+, a dopaminergic neurotoxin, in mitochondrial membra ne potential was investigated in dissociated cerebellar granule cells using rhodamine 123 and flow cytometry. MPP+ (1 mM) decreased the mito chondrial membrane potential by 30%. Antagonists of the NMDA receptor complex, such as MK-801 (IC50 value of 20.92 +/- 0.02 nM), 5,7-dichlor okynurenic acid (IC50 value of 6.46 +/- 1.06 mu M) and D-AP5 (IC50 val ue 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 o f this total agonist, it can be concluded that, in this preparation, M PP+ interacts with the NMDA receptor complex as a partial agonist. Thi s interaction could be the result of an allosteric modulation of the N MDA receptor complex by MPP+ The decrease of mitochondrial membrane po tential induced by MPP+ is antagonized by dibucaine, suggesting that t his effect is mediated by an activation of phospholipase A(2).