Conversion of the neurotoxic precursor 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine into its pyridinium metabolite by human platelet monoamine oxidase type B.
MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) causes selective and irreversible degeneration of the substantia nigra of human and non-human primates. In the central nervous system, the oxidative metabolism of MPTP to 1-methyl-4-phenyl-pyridinium (MPP+) by monoamine oxidase type B (MAO-B) seems to be a critical feature in the neurotoxic process. We now report that [3H]MPTP is rapidly converted in vitro into [3H]MPP+ by human platelet MAO-B. The formation of [3H]MPP+ in human platelets is prevented by specific MAO-B but not by MAO-A or by 5-hydroxytryptamine uptake inhibitors.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000097:blood*; D008995:Monoamine Oxidase / Q000097:blood*; D010084:Oxidation-Reduction; D011725:Pyridines / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000096:biosynthesis*; D012701:Serotonin / Q000378:metabolism
D007527:Isoenzymes; D011725:Pyridines; D011726:Pyridinium Compounds; D012701:Serotonin; C026560:1-(4-methoxyphenyl)pyridinium; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase