頁籤選單縮合
題 名 | Effect of Sertraline on Ca²⁺ Fluxes in Rabbit Corneal Epithelial Cells |
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作 者 | Yeh, Jeng-hsien; Sun, Te-kung; Chou, Chiang-ting; Chen, Wei-chuan; Lee, Jenn-kuen; Yeh, Hsiao-chun; Liang, Wei-zhe; Kuo, Chun-chi; Shieh, Pochuen; Kuo, Daih-huang; Jan, Chung-ren; | 書刊名 | The Chinese Journal of Physiology |
卷 期 | 58:2 2015.04[民104.04] |
頁 次 | 頁85-94 |
分類號 | 418.214 |
關鍵詞 | Ca²⁺; Corneal; Sertraline; SIRC; |
語 文 | 英文(English) |
英文摘要 | The effect of sertraline, a selective serotonin reuptake inhibitor (SSRI), on cytosolic free Ca2+ concentrations ([Ca2+]i ) in a rabbit corneal epithelial cell line (SIRC) is unclear. This study explored whether sertraline changed basal [Ca2+]i levels in suspended SIRC cells by using fura-2 as a Ca2+-sensitive fluorescent dye. Sertraline at concentrations between 10-100 μM increased [Ca2+]i in a concentrationdependent manner. The Ca2+ signal was reduced by 23% by removing extracellular Ca2+. Sertraline induced Mn2+ influx, leading to quench of fura-2 fluorescence, suggesting Ca2+ influx. This Ca2+ influx was inhibited by phospholipase A2 inhibitor aristolochic acid, but not by store-operated Ca2+ channel blockers and protein kinase C/A modulators. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin, cyclopiazonic acid or 2,5-di-tert-butylhydroquinone greatly inhibited sertraline-induced Ca2+ release. Inhibition of phospholipase C with U73122 abolished sertralineinduced [Ca2+]i rise. At concentrations of 5-50 μM, sertraline killed cells in a concentration-dependent manner. The cytotoxic effect of 25 μM sertraline was not reversed by prechelating cytosolic Ca2+ with BAPTA/AM. Collectively, in SIRC cells, sertraline induced [Ca2+]i rises by causing phospholipase Cdependent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-sensitive Ca2+ channels. Sertraline-caused cytotoxicity was mediated by Ca2+-independent pathways. |
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