1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridine (MPP+) cause rapid ATP depletion in isolated hepatocytes.
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its oxidized metabolite 1-methyl-4-phenylpyridine (MPP+) produce a rapid depletion of intracellular ATP in isolated rat hepatocytes. This effect was dose-dependent and was consistently observed before the onset of toxicity. The monoamine oxidase inhibitor pargyline provided significant protection against MPTP-induced cell death and ATP loss, but had no effect with MPP+. Thus, ATP depletion may play a critical role in MPTP toxicity, possibly via the metabolic production of MPP+.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002330:Carmustine / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010293:Pargyline / Q000494:pharmacology; D011725:Pyridines; D011726:Pyridinium Compounds; D051381:Rats; D013997:Time Factors
D011725:Pyridines; D011726:Pyridinium Compounds; D000255:Adenosine Triphosphate; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D002330:Carmustine