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  • Title: 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: Cheeseman AJ, Clark JB.
    Journal: J Neurochem; 1987 Apr; 48(4):1209-14. PubMed ID: 3102694.
    Abstract:
    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.
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