title: Effect of sertraline on Ca²⁺ fluxes in rabbit corneal epithelial cells.
abstract: 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 concentration-dependent 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 sertraline-induced [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 C-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ influx via phospholipase A₂-sensitive Ca²⁺ channels. Sertraline-caused cytotoxicity was mediated by Ca²⁺-independent pathways.
authors: Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan, Republic of China.|Department of Biological Science and Technology, Chung Hwa College of Medical Technology, Tainan 71703, Taiwan, Republic of China.
authors: Jeng-Hsien
authors: JH
authors: Yeh
authors: Divisions of Pediatrics, St. Joseph Hospital, Kaohsiung 80288, Taiwan, Republic of China.
authors: Te-Kung
authors: TK
authors: Sun
authors: Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan, Republic of China.|Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Chia-Yi 61363, Taiwan, Republic of China.
authors: Chiang-Ting
authors: CT
authors: Chou
authors: Divisions of Urology, St. Joseph Hospital, Kaohsiung 80288, Taiwan, Republic of China.
authors: Wei-Chuan
authors: WC
authors: Chen
authors: Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital Kaohsiung 81362, Taiwan, Republic of China.
authors: Jenn-Kuen
authors: JK
authors: Lee
authors: Department of Nursing, Meiho University, Pingtung 91202, Taiwan, Republic of China.
authors: Hsiao-Chun
authors: HC
authors: Yeh
authors: Department of Medical Education and Research, Kaohsiung Veterans General Hospital Kaohsiung 81362, Taiwan, Republic of China.
authors: Wei-Zhe
authors: WZ
authors: Liang
authors: Department of Nursing, Tzu Hui Institute of Technology, Pingtung 92641, Taiwan, Republic of China.
authors: Chun-Chi
authors: CC
authors: Kuo
authors: Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China.
authors: Pochuen
authors: P
authors: Shieh
authors: Department of Pharmacy, Tajen University, Pingtung 90741, Taiwan, Republic of China.
authors: Daih-Huang
authors: DH
authors: Kuo
authors: Department of Medical Education and Research, Kaohsiung Veterans General Hospital Kaohsiung 81362, Taiwan, Republic of China.
authors: Chung-Ren
authors: CR
authors: Jan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage; D020280:Sertraline / Q000008:administration & dosage*
chemical_list: D002118:Calcium; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline