title: Fendiline mobilizes intracellular Ca2+ in Chang liver cells.
abstract: 1. The effects of the antianginal drug fendiline (N-[3,3-diphenylpropyl]-alpha-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 micromol/L) increased [Ca2+](i) in a concentration-dependent manner, with an EC50 of 25 micromol/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 micromol/L)-induced release of intracellular Ca2+ was reduced by 65% following pretreatment with 1 micromol/L thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete Ca2+ stored in the endoplasmic reticulum. 5. After pretreatment with 10 micromol/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 micromol/L SKF96365, econazole, nifedipine or verapamil. 6. Fendiline (10 micromol/L)-induced release of intracellular Ca2+ was not altered by inhibition of phospholipase C with 2 micromol/L 1-(6-((17beta-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.
authors.affiliation: Department of Medicine, Kaohsiung Veterans General Hospital, 386 Ta Chung 1st Road, Kaohsiung, Taiwan 813, ROC.
authors.forename: J S
authors.initials: JS
authors.lastname: Cheng
authors.forename: K J
authors.initials: KJ
authors.lastname: Chou
authors.forename: J L
authors.initials: JL
authors.lastname: Wang
authors.forename: K C
authors.initials: KC
authors.lastname: Lee
authors.forename: L L
authors.initials: LL
authors.lastname: Tseng
authors.forename: K Y
authors.initials: KY
authors.lastname: Tang
authors.forename: J K
authors.initials: JK
authors.lastname: Huang
authors.forename: H T
authors.initials: HT
authors.lastname: Chang
authors.forename: W
authors.initials: W
authors.lastname: Su
authors.forename: Y P
authors.initials: YP
authors.lastname: Law
authors.forename: C R
authors.initials: CR
authors.lastname: Jan
mesh_terms: D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004963:Estrenes / Q000494:pharmacology; D005275:Fendiline / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D002121:Calcium Channel Blockers; D004963:Estrenes; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D005275:Fendiline; D002118:Calcium