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

Abstract

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 microM) increased [Ca2+]i with an EC50 of 25 microM. Removal of extracellular Ca2+ reduced the [Ca2+]i signals by 51 +/- 5%. Fendiline (10 microM)-induced Ca2+ release was abolished by pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Inhibition of phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122) did not alter 10 microM fendiline-induced Ca2+ release. Several other calmodulin antagonists, such as phenoxybenzamine (100-200 microM), trifluoperazine (5-50 microM), and fluphenazine-N-chloroethane (2-100 microM), 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.

• Authors: J S Cheng, J L Wang, Y K Lo, K J Chou, K C Lee, C P Liu, H T Chang, C R Jan
• Journal: Human & experimental toxicology (Hum Exp Toxicol) Vol. 20 Issue 7 Pg. 359-64 (Jul 2001) ISSN: 0960-3271 [Print] England
• PMID: 11530834 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium Channel Blockers
• Fendiline
• Calcium

Topics

• Calcium (pharmacokinetics)
• Calcium Channel Blockers (pharmacology)
• Carcinoma, Hepatocellular (pathology)
• Endoplasmic Reticulum (drug effects, physiology)
• Fendiline (pharmacology)
• Humans
• Liver Neoplasms (pathology)
• Signal Transduction
• Tumor Cells, Cultured