Effect of Nortriptyline on Ca(superscript 2+) Handling in SIRC Rabbit Corneal Epithelial Cells

10.4077/CJP.2010.AMK044

Kai-Hsien Chang；Hung-Pin Tan；Chun-Chi Kuo；Daih-Huang Kuo；Pochuen Shieh；Fu-An Chen；Chung-Ren Jan

Ca(superscript 2+) ； corneal epithelial cells ； nortriptyline ； SIRC cells

The Chinese Journal of Physiology

53卷3期（2010 / 06 / 01）

178 - 184

英文

To explore the effect of nortriptyline, a tricyclic antidepressant, on cytosolic free Ca(superscript 2+) concentrations ([Ca(superscript 2+)](subscript i)) in corneal epithelial cells, [Ca(superscript 2+)](subscript i) levels in suspended SIRC rabbit corneal epithelial cells were measured by using fura-2 as a Ca(superscript 2+)-sensitive fluorescent dye. Nortriptyline at concentrations between 20-200 μM increased [Ca(superscript 2+)](subscript i) in a concentration-dependent manner. The Ca(superscript 2+) signal was reduced partly by removing extracellular Ca(superscript 2+). Nortriptyline-induced Ca(superscript 2+) influx was inhibited by the store-operated Ca(superscript 2+) channel blockers econazole and SK&F96365, the phospholipase A2 inhibitor aristolochic acid, and alteration of activity of protein kinase C. In Ca(superscript 2+)-free medium, 200μM nortriptyline pretreatment greatly inhibited the rise of [Ca(superscript 2+)](subscript i) induced by the endoplasmic reticulum Ca(superscript 2+) pump inhibitor thapsigargin. Conversely, pretreatment with thapsigargin or 2, 5-di-tert-butylhydroquinone (BHQ; another endoplasmic reticulum Ca(superscript 2+) pump inhibitor) nearly abolished nortriptyline-induced [Ca(superscript 2+)](subscript i) rise. Inhibition of phospholipase C with U73122 decreased nortriptyline-induced [Ca(superscript 2+)](subscript i) rise by 75%. Taken together, nortriptyline induced [Ca(superscript 2+)](subscript i) rises in SIRC cells by causing phospholipase C-dependent Ca(superscript 2+) release from the endoplasmic reticulum and Ca(superscript 2+) influx via store-operated Ca(superscript 2+) channels.

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