title: The effect of antiparkinsonian drugs on oxidative stress induced pathological [3H]dopamine efflux after in vitro rotenone exposure in rat striatal slices.
abstract: An in vitro model of mitochondrial dysfunction with subsequent oxidative stress was elaborated and utilized to study the effect of drugs, currently used for the treatment of Parkinson's disease, on pathological H(2)O(2)-evoked [(3)H]dopamine efflux and the formation of toxic dopamine metabolites in rat striatal slices. 60 min rotenone (0.1-10 muM) pretreatment decreased dopamine content and [(3)H]dopamine uptake, as well as ATP level and energy charge of the slices. In addition, a robust potentiation of H(2)O(2)-evoked [(3)H]dopamine efflux and the formation of dopamine quinone in the effluent was detected. l-DOPA (200 muM) markedly elevated resting but not 100 muM H(2)O(2)-evoked and electrically-induced [(3)H]dopamine efflux. Furthermore, l-DOPA promoted the formation of dopamine quinone. Ropinirole (100 nM) did not affect resting and H(2)O(2)-evoked [(3)H]dopamine efflux and inhibited the electrically evoked release only in untreated slices. l-deprenyl, at concentration of 0.01 muM potentiated, whilst between 1 and 50 muM diminished H(2)O(2)-evoked [(3)H]dopamine efflux. Rasagiline (0.01-50 muM) slightly inhibited H(2)O(2)-evoked [(3)H]dopamine efflux, and it was able to prevent the generation of dopamine quinone. Neither of the drugs was able to suppress both the pathological H(2)O(2)-evoked [(3)H]dopamine efflux and the formation of dopamine quinone with simultaneous augmentation of electrically evoked [(3)H]dopamine release what should be a future concept of antiparkinsonian drug-design.
authors.affiliation: Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Szigony u. 43, Hungary.
authors.forename: Elisaveta
authors.initials: E
authors.lastname: Milusheva
authors.forename: Mária
authors.initials: M
authors.lastname: Baranyi
authors.forename: Eszter
authors.initials: E
authors.lastname: Kormos
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hracskó
authors.forename: E
authors.initials: E
authors.lastname: Sylvester Vizi
authors.forename: Beáta
authors.initials: B
authors.lastname: Sperlágh
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000494:pharmacology*
chemical_list: D000978:Antiparkinson Agents; D012402:Rotenone; D004298:Dopamine