MPP(+) SELECTIVELY AFFECTS CALCIUM HOMEOSTASIS IN MESENCEPHALIC CELL-CULTURES FROM EMBRYONAL C57/B16 MICE

1-Methyl-4-phenylpyridinium (MPP(+)), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) serves as a valuable tool in animal models of Parkinson's disease. Primary cell cultures of mesencephalon from C57/B16 mice were used to investigate the effects of various dopaminergic neurotoxins on the intracellular calcium metabolism. MPP(+) ws compared to its precursor MPTP and a structural analogue paraquat (methylviologen). Direct addition of these neurotoxins (10 mu M) to fura-2-labeled cells did not change intracellular calcium concentrations ill the presence of 1 mM extracellular calcium. When mesencephalic neurons were exposed to the compounds for 24 hours, only MPP(+) led to an increase in calcium concentration in the absence and presence of extracellular calcium (36%, p < 0.05 and 47%, p < 0.01 versus control group). Intracellular calcium concentrations in cortical cultures devoid of dopaminergic cells were not changed by the above neurotoxins. Thus MPP(+) is shown to selectively increase intracellular calcium concentrations in mesencephalic cultures.