Effects of iptakalim on rotenone-induced cytotoxicity and dopamine release from PC12 cells.
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.
Yang
Yong
Y
Department of Pharmacology and Neurobiology, Nanjing Medical University, Nanjing 210029, China.
Liu
Xing
X
Ding
Jian-Hua
JH
Sun
Jing
J
Long
Yan
Y
Wang
Fang
F
Yao
Hong-Hong
HH
Hu
Gang
G
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors; D015640:Ion Channel Gating; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010879:Piperazines; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D012402:Rotenone / Q000633:toxicity*
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D010879:Piperazines; D015221:Potassium Channels; D012402:Rotenone; D000255:Adenosine Triphosphate; C043425:vanoxerine; D042967:Electron Transport Complex I; D004298:Dopamine