期刊
NEUROPHARMACOLOGY
卷 58, 期 4-5, 页码 816-825出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2009.11.017
关键词
Rotenone; Oxidative stress; H2O2; Dopamine release; Antiparkinsonian drugs; Striatum
资金
- Hungarian National Office for Research and Development [RET1427/2004]
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 H2O2-evoked [H-3]dopamine efflux and the formation of toxic dopamine metabolites in rat striatal slices. 60 min rotenone (0.1-10 mu M) pretreatment decreased dopamine content and [H-3]dopamine uptake, as well as ATP level and energy charge of the slices. In addition, a robust potentiation of H2O2-evoked [H-3]dopamine efflux and the formation of dopamine quinone in the effluent was detected. L-DOPA (200 mu M) markedly elevated resting but not 100 mu M H2O2-evoked and electrically-induced [H-3]dopamine efflux. Furthermore, L-DOPA promoted the formation of dopamine quinone. Ropinirole (100 nM) did not affect resting and H2O2-evoked [H-3]dopamine efflux and inhibited the electrically evoked release only in untreated slices. L-deprenyl, at concentration of 0.01 mu M potentiated, whilst between 1 and 50 mu M diminished H2O2-evoked [H-3]dopamine efflux. Rasagiline (0.01-50 mu M) slightly inhibited H2O2-evoked [H-3]dopamine efflux, and it was able to prevent the generation of dopamine quinone. Neither of the drugs was able to suppress both the pathological H2O2-evoked [H-3]dopamine efflux and the formation of dopamine quinone with simultaneous augmentation of electrically evoked [H-3]dopamine release what should be a future concept of antiparkinsonian drug-design. (C) 2009 Elsevier Ltd. All rights reserved.
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