Effect of nortriptyline on Ca 2+ handling in SIRC rabbit corneal epithelial cells

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

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

9 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)178-184
Number of pages7
JournalChinese Journal of Physiology
Volume53
Issue number3
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • Corneal epithelial cells
  • Nortriptyline
  • SIRC cells

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