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  • Title: Effects of iptakalim on rotenone-induced cytotoxicity and dopamine release from PC12 cells.
    Author: Yang Y, Liu X, Ding JH, Sun J, Long Y, Wang F, Yao HH, Hu G.
    Journal: Neurosci Lett; 2004 Aug 05; 366(1):53-7. PubMed ID: 15265589.
    Abstract:
    Parkinson's disease is characterized by an extensive loss of dopaminergic neurons in the substantia nigra pars compacta. The final common pathway in the demise of these cells may involve dopamine-dependent oxidative stress. Previous studies revealed a new neuronal protective role of ATP-sensitive potassium channel openers. But the exact mechanism is still unknown. In the present study, the neuroprotective effect of iptakalim, a novel ATP-sensitive potassium channel opener, was studied against rotenone-induced cytotoxicity in rat dopaminergic PC12 cells. Rotenone decreased cell viability significantly after 48 h exposure and induced dopamine release from PC12 cells concentration-dependently. Iptakalim significantly enhanced dopamine uptake and alleviated rotenone-induced PC12 cells death and reduced dopamine release induced by rotenone or GBR-12909, a classical dopamine transporter inhibitor. These results suggest that iptakalim may open mitochondrial K(ATP) channels to modulate dopamine transporter and reduce extracellular dopamine levels, thereby it protecting PC12 cells against rotenone-induced injury.
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