Mitochondrial factors involved in Parkinson's disease by MPTP toxicity in Macaca fascicularis and drug effect.
The maximal rates (Vmax) of some mitochondrial enzyme activities related to energy transduction (citrate synthase, succinate dehydrogenase, malate dehydrogenase, NADH-cytochrome c reductase, cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase, glutamate-pyruvate- and glutamate-oxaloacetate- transaminases) were evaluated in non-synaptic ("free") and intrasynaptic "light" and "heavy" mitochondria from hippocampus of Macaca fascicularis (Cynomolgus monkey). The different mitochondrial populations were isolated from the hippocampus of monkeys treated p.o. with dihydroergocryptine at a dose of 12 mg/kg/day before and during the induction of a Parkinson's-like syndrome by MPTP administration (i.v., 0.3 mg/kg/day for 5 days). The MPTP administration modified the activity of some enzymes related to the metabolism of glutamate and the activity of succinate dehydrogenase on selected types of mitochondria. Pharmacological treatment by dihydroergocryptine promoted return to the steady-state levels of most enzymes, demonstrating a protective effect on these biochemical parameters.
Villa
R F
RF
Institute of Pharmacology, Faculty of Science, University of Pavia, Italy.
Arnaboldi
R
R
Ghigini
B
B
Gorini
A
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D004088:Dihydroergotoxine / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D020267:MPTP Poisoning; D008252:Macaca fascicularis; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D013574:Synaptosomes / Q000201:enzymology
D000596:Amino Acids; D004088:Dihydroergotoxine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine