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 b y using fura-2 as a fluorescent Ca2+ dye. Fendiline (1-100 muM) increased [ Ca2+](i) with an EC50 of 25 muM. Removal of extracellular Ca2+ reduced the [Ca2+], signals by 51 +/- 5%. Fendiline (10 muM)-induced Ca2+ release was a bolished by pretreatment with 1 muM thapsigargin (an endoplasmic reticulum. Ca2+ pump inhibitor). Inhibition of phospholipase C with 2 muM 1-(6-((17 b eta -3-methoxyestra-1,3,5(10) -trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dion e (U73122) did not alter 10 muM fendiline induced Ca2+ release. Several oth er calmodulin antagonists, such as phenoxybenzamine (100-200 muM), trifluop erazine (5-50 muM), and fluphenazine-N-chloroethane [2-100 muM), had no eff ect 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 c almodulin.