MPP+ selectively affects calcium homeostasis in mesencephalic cell cultures from embryonal C57/Bl6 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/Bl6 mice were used to investigate the effects of various dopaminergic neurotoxins on the intracellular calcium metabolism. MPP+ was compared to its precursor MPTP and a structural analogue paraquat (methylviologen). Direct addition of these neurotoxins (10 microM) to fura-2-labeled cells did not change intracellular calcium concentrations in 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.
Chen
T S
TS
Institute of Medical Chemistry, University of Veterinary Medicine, Vienna, Austria.
Koutsilieri
E
E
Rausch
W D
WD
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D006706:Homeostasis; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice / Q000196:embryology; D008810:Mice, Inbred C57BL; D010269:Paraquat / Q000494:pharmacology
D015259:Dopamine Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010269:Paraquat; D015655:1-Methyl-4-phenylpyridinium; D002118:Calcium