The biogenic trace amine tyramine induces a pronounced hydroxyl radical production via a monoamine oxidase dependent mechanism: an in vivo microdialysis study in mouse striatum.
Tyramine is a biogenic trace amine that releases monoamines and is a good substrate for monoamine oxidase (MAO)-A/B. Here we investigated whether tyramine affects hydroxyl radical formation in the intact and lesioned dopaminergic system. Male C57bl/6 mice received systemic and local tyramine administrations. Hydroxyl radical formation and dopamine (DA) overflow were determined in the striatum using in vivo microdialysis in combination with the salicylate hydroxylation assay. Systemic injection of tyramine neither enhanced extracellular dopamine nor induced hydroxyl radical formation. In contrast, when tyramine was incorporated into the dialysate fluid, hydroxyl radical formation and extracellular dopamine levels were significantly enhanced. Systemic pretreatment with the MAO-A/B inhibitor tranylcypromine or with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) significantly diminished the tyramine-induced hydroxyl radical formation by 73.1% and 80.6%, respectively. We conclude that the mechanism of tyramine-induced hydroxyl free radical formation involves MAO metabolism and requires an intact dopaminergic system. Pharmacological intervention on the MAO-mediated formation of hydroxyl free radicals seems to be a promising strategy to prevent oxidative damage in the nigrostriatal dopaminergic system.
Schmidt
Nicole
N
Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Ketzerbach 63, D-35032 Marburg, Germany.
Ferger
Boris
B
D000818:Animals; D005609:Free Radicals / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D051379:Mice; D017551:Microdialysis / Q000379:methods*; D008995:Monoamine Oxidase / Q000096:biosynthesis*; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D014191:Tranylcypromine / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology*
D005609:Free Radicals; D017665:Hydroxyl Radical; D014191:Tranylcypromine; D008995:Monoamine Oxidase; D014439:Tyramine