Effect of sertraline on Ca²âº fluxes in rabbit corneal epithelial cells.
Chin J Physiol
; 58(2): 85-94, 2015 Apr 30.
Article
em En
| MEDLINE
| ID: mdl-25858469
ABSTRACT
The effect of sertraline, a selective serotonin reuptake inhibitor (SSRI), on cytosolic free Ca²âº concentrations ([Ca²âº](i)) in a rabbit corneal epithelial cell line (SIRC) is unclear. This study explored whether sertraline changed basal [Ca²âº](i) levels in suspended SIRC cells by using fura-2 as a Ca²âº-sensitive fluorescent dye. Sertraline at concentrations between 10-100 µM increased [Ca²âº](i) in a concentration-dependent manner. The Ca²âº signal was reduced by 23% by removing extracellular Ca²âº. Sertraline induced Mn²âº influx, leading to quench of fura-2 fluorescence, suggesting Ca²âº influx. This Ca²âº influx was inhibited by phospholipase A2 inhibitor aristolochic acid, but not by store-operated Ca²âº channel blockers and protein kinase C/A modulators. In Ca²âº-free medium, pretreatment with the endoplasmic reticulum Ca²âº pump inhibitor thapsigargin, cyclopiazonic acid or 2,5-di-tert-butylhydroquinone greatly inhibited sertraline-induced Ca²âº release. Inhibition of phospholipase C with U73122 abolished sertraline-induced [Ca²âº](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 Ca²âº with BAPTA/AM. Collectively, in SIRC cells, sertraline induced [Ca²âº](i) rises by causing phospholipase C-dependent Ca²âº release from the endoplasmic reticulum and Ca²âº influx via phospholipase A2-sensitive Ca²âº channels. Sertraline-caused cytotoxicity was mediated by Ca²âº-independent pathways.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cálcio
/
Epitélio Corneano
/
Sertralina
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Sinalização do Cálcio
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Células Epiteliais
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article