Manganese mimics the action of 1-methyl-4-phenylpyridinium ion, a dopaminergic neurotoxin, in rat striatal tissue slices.
Manganese and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are known to induce neurological pathologies similar to that of parkinsonism. Previous studies performed in rat striatal slices have shown that MPTP and related compounds inhibit tyrosine hydroxylation, a rate-limiting step of dopamine biosynthesis. Here, we reported that manganese inhibited tyrosine hydroxylation in rat striatal slices. In addition, manganese caused increase in the levels of lactate indicating that aerobic glycolysis was inhibited in striatal slices. This inhibition was unique to manganese since other divalent cations, such as magnesium and zinc, did not increase lactate concentrations. These results suggest that the mechanisms by which manganese produces dysfunction of the nervous system are similar to those of MPTP.
Hirata
Y
Y
Laboratory for Genes of Motor Systems, Bio-Mimetic Control Research Center, RIKEN, 2271-130, Anagahora, Shimoshidami, Moriyama, 463-0003, Nagoya, Japan.yoko@bmc.riken.go.jp
Kiuchi
K
K
Nagatsu
T
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D004295:Dihydroxyphenylalanine / Q000096:biosynthesis / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D006900:Hydroxylation / Q000187:drug effects; D019344:Lactic Acid / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D020149:Manganese Poisoning / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism
D009498:Neurotoxins; D019344:Lactic Acid; D014443:Tyrosine; D008345:Manganese; D004295:Dihydroxyphenylalanine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine