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

1-Methyl-4-phenylpyridinium (MPP(+)), the active metabolite of 1-methy l-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) serves as a valuable tool in animal models of Parkinson's disease. Primary cell cultures of mes encephalon from C57/B16 mice were used to investigate the effects of v arious dopaminergic neurotoxins on the intracellular calcium metabolis m. 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 conce ntrations ill the presence of 1 mM extracellular calcium. When mesence phalic neurons were exposed to the compounds for 24 hours, only MPP(+) led to an increase in calcium concentration in the absence and presen ce of extracellular calcium (36%, p < 0.05 and 47%, p < 0.01 versus co ntrol group). Intracellular calcium concentrations in cortical culture s devoid of dopaminergic cells were not changed by the above neurotoxi ns. Thus MPP(+) is shown to selectively increase intracellular calcium concentrations in mesencephalic cultures.