The effect of antiparkinsonian drugs on oxidative stress induced pathological [3H]dopamine efflux after in vitro rotenone exposure in rat striatal slices.
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.
Milusheva
Elisaveta
E
Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Szigony u. 43, Hungary.
Baranyi
Mária
M
Kormos
Eszter
E
Hracskó
Zsuzsanna
Z
Sylvester Vizi
E
E
Sperlágh
Beáta
B
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*
D000978:Antiparkinson Agents; D012402:Rotenone; D004298:Dopamine