Effects of the antianginal drug fendiline on Ca²⁺ movement in hepatoma cells

This study investigated the effect of the anti-anginal drug, fendiline, on intracellular free Ca²⁺ levels ([Ca²⁺]_i) in HA/22 human hepatoma cells by using fura-2 as a fluorescent Ca²⁺ dye. Fendiline (1-100 μM) increased [Ca²⁺]_i with an EC₅₀ of 25 μM. Removal of extracellular Ca²⁺ reduced the [Ca²⁺]_i signals by 51 ± 5%. Fendiline (10 μM)-induced Ca²⁺ release was abolished by pretreatment with 1 μM thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor). Inhibition of 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) did not alter 10 μM fendiline-induced Ca²⁺ release. Several other calmodulin antagonists, such as phenoxybenzamine (100-200 μM), trifluoperazine (5-50 μM), and fluphenazine-N-chloroethane (2-100 μM), had no effect on [Ca²⁺]_i. Together, it was found that fendiline increased [Ca²⁺]_i in human hepatoma cells by discharging Ca²⁺ from the endoplasmic reticulum in an inositol 1,4,5-trisphosphate-independent manner and by inducing Ca²⁺ entry. This effect of fendiline does not appear to be via antagonism of calmodulin.