Studies on the metabolism and toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in cultures of embryonic rat mesencephalon.
The metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was studied in dissociated cell cultures prepared from embryonic rat mesencephalon. MPTP was added to the feeding medium and at the end of the incubation period MPTP was separated from the water-soluble metabolite by ether extraction. Our results demonstrate that, in cultures, MPTP is oxidized predominantly by monoamine oxidase B, since deprenyl but not clorgyline had an inhibitory effect on its metabolism. The metabolite of MPTP diffuses freely in the feeding medium (99% of the total) and its concentration increases with time. The concentration of the metabolite can be increased by increasing the number of cells plated into the tissue culture dish and the toxicity to dopamine neurons depends on the amount of metabolite accumulated in the feeding medium. The metabolism of MPTP is reduced by decreasing the number of glial cells present in the cultures.
Mytilineou
C
C
Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029.
Friedman
L
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D003470:Culture Media; D005467:Floxuridine / Q000494:pharmacology; D008636:Mesencephalon / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology; D011725:Pyridines / Q000378:metabolism* / Q000506:poisoning; D051381:Rats; D011919:Rats, Inbred Strains
D003470:Culture Media; D008996:Monoamine Oxidase Inhibitors; D011725:Pyridines; D005467:Floxuridine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine