Comparison of intra- and extrasynaptosomal monoamine oxidase-A and -B activities in the striatum and frontal cortex of two mice strains with different sensitivities to the neurotoxic actions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
Conditions for the assay of the intra- and extrasynaptosomal rates of deamination of dopamine and noradrenaline by the two forms of monoamine oxidase (MAO) have been determined in striatal and frontal cortical homogenates, respectively, from C57 BL/6 mice. The activities obtained were compared with the corresponding activities found for NMRI mice, a strain less sensitive to the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) than the C57 BL/6 strain. In both strains, the intra- and extrasynaptosomal deamination of dopamine in the striatal homogenates was brought about predominantly by MAO-A. No significant differences between the two strains were found for the intra- or extrasynaptosomal MAO-A or -B activities towards dopamine in striatal homogenates. On the other hand, the striatal dopamine concentrations were higher in the C57 BL/6 mice than in the NMRI mice. The concentrations of the dopamine metabolites DOPAC and HVA were similarly higher, suggesting that the rate of turnover of dopamine is the same for the two strains. In frontal cortical homogenates, MAO-A predominated in the deamination of noradrenaline both intra- and extrasynaptosomally. The extrasynaptosomal rates of deamination of noradrenaline were similar in the two mice strains, whereas the intrasynaptosomal MAO-A activity was significantly higher for the C57 BL/6 mice. These results concur with and extend to the noradrenergic system the conclusion previously made by Jossan et al. (1987) for the dopaminergic system that although MAO-B activity is necessary for expression of MPTP neurotoxicity, it is not the rate-limiting step for the development of the neurotoxic effects.
Stenström
A
A
Department of Pharmacology, University of Umeå, Sweden.
Sundström
E
E
Fowler
C J
CJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology*; D003010:Clorgyline / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology*; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011725:Pyridines / Q000633:toxicity*; D013045:Species Specificity; D013574:Synaptosomes / Q000201:enzymology*
D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D003010:Clorgyline; D004298:Dopamine; D009638:Norepinephrine