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.
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.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000109:Acetylcholine / Q000096:biosynthesis*; D000499:Allylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002952:Citric Acid Cycle / Q000187:drug effects; D004027:Diencephalon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D016660:NAD(P)H Dehydrogenase (Quinone); D010293:Pargyline / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D011808:Quinone Reductases / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000378:metabolism*; D013687:Telencephalon / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D011725:Pyridines; D011726:Pyridinium Compounds; D000499:Allylamine; C040051:2-(3,4-dimethoxyphenyl)-3-fluoroallylamine; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D005947:Glucose; D000109:Acetylcholine; D015655:1-Methyl-4-phenylpyridinium