title: Effects of iptakalim on rotenone-induced cytotoxicity and dopamine release from PC12 cells.
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.
authors.affiliation: Department of Pharmacology and Neurobiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Ding
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Long
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Yao
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
mesh_terms: 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*
chemical_list: 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