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Effects of 1‐Methyl‐4‐Phenyl‐1,2,5,6‐Tetrahydropyridine and Its Metabolite 1‐Methyl‐4‐Phenylpyridine on Acetylcholine Synthesis in Synaptosomes from Rat Forebrain
Author(s) -
Cheeseman Andrea J.,
Clark John B.
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb05648.x
Subject(s) - mptp , pargyline , monoamine oxidase , metabolite , chemistry , acetylcholine , biochemistry , dopaminergic , dopamine , pharmacology , biology , endocrinology , enzyme
1‐Methyl‐4‐phenyl‐1,2,5,6‐tetrahydropyridine (MPTP) and its metabolite, 1‐methyl‐4‐phenylpyridine (MPP + ), have been shown to cause a number of lesions in dopaminergic pathways of the nigro‐striatal region of the brain. However, data on the effects of these neurotoxins on other aspects of brain metabolism are scarce. The data presented here show that MPTP and MPP + inhibit glucose oxidation via the tricarboxylic acid cycle, and acetylcholine synthesis in synaptosomal preparations from rat forebrain. Monoamine oxidase B inhibitors (e.g., pargyline, MDL 72145) relieve the inhibition caused by MPTP but not MPP + . The inhibitory effects of MPP + on glucose oxidation and acetylcholine synthesis are a consequence of the decreased glucose metabolism in synaptosomes and are consistent with its role as an inhibitor of the Complex I (NADH‐CoQ reductase) of the mitochondrial respiratory chain.