Add time:09/10/2019         Source:sciencedirect.com

The effect of the anti-anginal drug Fendiline (cas 13042-18-7) on intracellular free Ca2+ levels ([Ca2+]i) in a rabbit corneal epithelial cell line (SIRC) was explored using fura-2 as a fluorescent Ca2+ indicator. At a concentration above 1 μM, fendiline increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 7 μM. The [Ca2+]i response consisted of an immediate rise and an elevated phase. Extracellular Ca2+ removal decreased half of the [Ca2+]i signal. Fendiline induced quench of fura-2 fluorescence by Mn2+ (50 μM), suggesting the presence of Ca2+ influx across the plasma membrane. This Ca2+ influx was abolished by La3+ (50 μM), but was insensitive to dihydropyridines, verapamil and diltiazem. Fendiline (10 μM)-induced store Ca2+ release was largely reduced by pretreatment with thapsigargin (1 μM) (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete the endoplasmic reticulum Ca2+. Conversely, pretreatment with 10 μM fendiline abolished thapsigargin-induced Ca2+ release. Fendiline (10 μM)-induced Ca2+ release was not altered by inhibiting phospholipase C with 2 μM 1-(6-((17β-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). Cumulatively, this study shows that fendiline induced concentration-dependent [Ca2+]i increases in corneal epithelial cells by releasing the endoplasmic reticulum Ca2+ in a phospholipase C-independent manner, and by causing Ca2+ influx.

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