Indapamide induces apoptosis of GH3 pituitary cells independently of its inhibition of voltage-dependent K⁺ currents

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• 作者：De-Li Dong ; Qing-Hui Wang ; Peng Yue ; Jun-Dong Jiao ; Rui-Min Gu and Bao-Feng Yang
• 关键词：Indapamide ; Pituitary cell ; Voltage-dependent K⁺ current ; Apoptosis
• 刊名：European Journal of Pharmacology
• 出版年：2006
• 出版时间：24 April 2006
• 年：2006
• 卷：536
• 期：1-2
• 页码：78-84
• 全文大小：852 K

文摘

Indapamide blocks multiple voltage-dependent K⁺ currents (K_v) in the heart and K_v have an important role in cell proliferation and apoptosis, so the aim of this work was to study the effects of indapamide on K_v and the viability of GH3 cells. Indapamide inhibited K_v of GH3 cells and the inhibition was irreversible after a 10-min washout when more than 250 μM indapamide was used. Indapamide reduced the viability of GH3 cells in a concentration-dependent manner. The decreased cell viability was because indapamide induced cell apoptosis, or even necrosis at higher concentrations. HepG2 cells, which express no apparent K_v, were used to determine the association between inhibition of K_v and the apoptotic action of indapamide. Indapamide had a similar action on cell viability and apoptosis of HepG2 cells. 4-Aminopyridine, the voltage-dependent K⁺ channel blocker, inhibited K_v of GH3 cells but did not induce the cell apoptosis. We concluded that while indapamide inhibited K_v and induced apoptosis of GH3 cells, the apoptotic action of indapamide was not associated with its inhibition of K_v.