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

Department of Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan

J-L Wang

Department of Rehabilitation, School of Medicine, National Yang Ming University, Taipei, Taiwan

Y-K Lo

K-J Chou

K-C Lee

C-P Liu

Department of Medicine, School of Medicine, National Yang Ming University, Taipei, Taiwan

H-T Chang

Department of Surgery, School of Medicine, National Yang Ming University, Taipei, Taiwan

C-R Jan

Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Department of Biology and Institute of Life Sciences, National Sun Yat Sen University, Kaohsiung, Taiwan; Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta Chung 1st Road, Kaohsiung 813, Taiwan

This study investigated the effect of the anti-anginal drug, fendiline, on intracellular free Ca²⁺ levels ([Ca²⁺]_i)inHA/ 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-((17ß 3 methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H pyrrole-2,5-dione (U73122) did not alter 10 µM fendilineinducedCa²⁺ release.Severalothercalmodulinantagonists, such as phenoxybenzamine (100-200 µM), trifluoperazine (5-50 µM),andfluphenazine N-chloroethane(2-100 µM), hadno effect on[Ca²⁺]_i. Together, it wasfound 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.

Key Words: Ca2+ signaling • fendiline • fura-2 • hepatoma cells • Ca2+stores

Human & Experimental Toxicology, Vol. 20, No. 7, 359-364 (2001)
DOI: 10.1191/096032701680350523


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