Fendiline Mobilizes Intracellular Ca2+ In Chang Liver Cells

• Published in: Clinical and experimental pharmacology & physiology 2001-09, Vol.28 (9), p.729-733
• Main Authors: Cheng, Jin-Shiung, Chou, Kang-Ju, Wang, Jue-Long, Lee, Kam-Chung, Tseng, Li-Ling, Tang, Kwong-Yui, Huang, Jong-Khing, Chang, Hong-Tai, Su, Warren, Law, Yee-Ping, Jan, Chung-Ren
• Format: Article
• Language: English
• Subjects: Ca2+ signalling; Calcium - metabolism; Calcium - pharmacology; Calcium Channel Blockers - pharmacology; Carbonyl Cyanide m-Chlorophenyl Hydrazone - pharmacology; Cell Line; Chang liver; Dose-Response Relationship, Drug; Estrenes - pharmacology; fendiline; Fendiline - pharmacology; hepatocytes; Humans; Imidazoles - pharmacology; Inositol 1,4,5-Trisphosphate - metabolism; intracellular Ca2; Liver - cytology; Liver - drug effects; Liver - metabolism; Phosphodiesterase Inhibitors - pharmacology; Pyrrolidinones - pharmacology; Thapsigargin - pharmacology; Time Factors; Type C Phospholipases - antagonists & inhibitors
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1046/j.1440-1681.2001.03510.x

SUMMARY 1. The effects of the antianginal drug fendiline (N‐[3,3‐diphenylpropyl]‐α‐methyl‐benzylamine) on intracellular free Ca2+ levels ([Ca2+]i) in Chang liver cells were evaluated using fura‐2 as a fluorescent Ca2+ indicator. 2. Fendiline (1–100 μmol/L) increased [Ca2+]i in a concentration‐dependent manner, with an EC50 of 25 μmol/L. 3. The [Ca2+]i response was composed of an initial rise and a slow decay to a sustained phase. Removal of extracellular Ca2+ partly reduced the [Ca2+]i signals. 4. Fendiline (10 μmol/L)‐induced release of intracellular Ca2+ was reduced by 65% following pretreatment with 1 μmol/L thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete Ca2+ stored in the endoplasmic reticulum. 5. After pretreatment with 10 μmol/L fendiline in Ca2+‐free medium for several minutes, addition of 3 mmol/L Ca2+ induced an increase in [Ca2+]i of a magnitude four‐fold greater than control. This increase in [Ca2+]i was not reduced by 10 μmol/L SKF96365, econazole, nifedipine or verapamil. 6. Fendiline (10 μmol/L)‐induced release of intracellular Ca2+ was not altered by inhibition of phospholipase C with 2 μmol/L 1‐(6‐((17β‐3‐methoxyestra‐1,3,5(10)‐trien‐17‐yl)amino) hexyl)‐1H‐pyrrole‐2,5‐dione (U73122). 7. The results of the present study show that fendiline induces an increase in [Ca2+]i in Chang liver cells by releasing stored Ca2+ in an inositol 1,4,5‐trisphosphate‐independent manner and by causing extracellular Ca2+ influx.