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 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.
Cheng
J S
JS
Department of Medicine, Kaohsiung Veterans General Hospital, Taiwan.
Wang
J L
JL
Lo
Y K
YK
Chou
K J
KJ
Lee
K C
KC
Liu
C P
CP
Chang
H T
HT
Jan
C R
CR
D002118:Calcium / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology; D005275:Fendiline / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D005275:Fendiline; D002118:Calcium