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Effect of sertraline on Ca²⁺ fluxes in rabbit corneal epithelial cells.
- Source :
-
The Chinese journal of physiology [Chin J Physiol] 2015 Apr 30; Vol. 58 (2), pp. 85-94. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Calcium Signaling drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Epithelial Cells drug effects
Epithelium, Corneal drug effects
Rabbits
Selective Serotonin Reuptake Inhibitors administration & dosage
Calcium metabolism
Calcium Signaling physiology
Epithelial Cells metabolism
Epithelium, Corneal cytology
Epithelium, Corneal metabolism
Sertraline administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 0304-4920
- Volume :
- 58
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Chinese journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 25858469
- Full Text :
- https://doi.org/10.4077/CJP.2015.BAC255