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N ‐Methyl‐4‐phenylpyridine (MMP + together with 6‐hydroxydopamine or dopamine stimulates Ca 2+ release from mitochondria
Author(s) -
Frei Balz,
Richter Christoph
Publication year - 1986
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(86)81192-9
Subject(s) - hydroxydopamine , dopamine , chemistry , mitochondrion , biochemistry , endocrinology , biology , dopaminergic
The nigrostriatal neurotoxin N ‐methyl‐1,2,3,6‐tetrahydropyridine (MPTP) causes Parkinsonism in humans and laboratory animals. MPTP neurotoxicity is dependent on its oxidation to N ‐methyl‐4‐phenylpyridine (MPP + ). The mechanism by which MPP + causes destruction of dopamine‐containing nigrostriatal cells is unknown. Here we show that MPP + but not MPTP is taken up by energized mitochondria. MPP + in the presence of dopamine and particularly of 6‐hydroxydopamine stimulates Ca 2+ release from mitochondria. Ca 2+ release is accompanied by hydrolysis of intramitochondrial pyridine nucleotides. Our findings suggest that the MPTP‐induced model of Parkinson's disease may be due to a disturbed Ca 2+ homeostasis in dopamine neurons.