Parkinson-like disease by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in Macaca fascicularis: synaptosomal metabolism and action of dihydroergocriptine.
The maximal rates (Vmax) of some enzyme activities related to synaptosomal energy metabolism were studied in different types of synaptosomes from cerebellar cortex of Macaca Fascicularis (Cynomolgus monkey). Different synaptosomal populations, namely "large" and "small" synaptosomes, were isolated from the anterior lobule of the cerebellar cortex of monkeys treated p.o. with dihydroergocriptine at the 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 enzymes were chosen according to their regulatory role and as markers of the following metabolic pathways: (a) glycolysis ((hexokinase, phosphofructokinase, lactate dehydrogenase), (b) Krebs' (TCA) cycle (citrate synthase, malate dehydrogenase), (c) amino acid, glutamate metabolism (glutamate dehydrogenase, glutamate-pyruvate- and glutamate-oxaloacetate-transaminases), (d) acetylcholine catabolism (acetylcholinesterase) and (e) ATPases, i.e. Na(+)-K(+)-ATPase, Mg(2+)-ATP synthetase, Mg(2+)-ATPase, Ca(2+)-Mg(2+)-ATPase and Ca(2+)-ATPase Low and High affinity for Ca2+. The MPTP administration modified the activities of citrate synthase, malate dehydrogenase, Na(+)-K(+)-ATPase, acetylcholinesterase and glutamate-oxaloacetate transaminase only on selected types of synaptosomes. Pharmacological treatment by dihydroergocriptine was able to recovery at the steady-state levels the activities of these enzymes, thus demonstrating a partial 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
D000109:Acetylcholine / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002525:Cerebellar Cortex / Q000378:metabolism*; D002952:Citric Acid Cycle; D004088:Dihydroergotoxine / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D006019:Glycolysis; D020267:MPTP Poisoning; D008252:Macaca fascicularis; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000596:Amino Acids; D004088:Dihydroergotoxine; D000251:Adenosine Triphosphatases; D000109:Acetylcholine