The anti-anginal drug fendiline increases intracellular Ca(2+) levels in MG63 human osteosarcoma cells.
The effect of fendiline, an anti-anginal drug, on cytosolic free Ca(2+) levels ([Ca(2+)](i)) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca(2+) indicator. Fendiline at concentrations between 1 and 200 microM increased [Ca(2+)](i) in a concentration-dependent manner and the signal saturated at 100 microM. The Ca(2+) signal was inhibited by 65+/-5% by Ca(2+) removal and by 38+/-5% by 10 microM nifedipine, but was unchanged by 10 microM La(3+) or verapamil. In Ca(2+)-free medium, pre-treatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) to deplete the endoplasmic reticulum Ca(2+) store inhibited fendiline-induced intracellular Ca(2+) release. The Ca(2+) release induced by 50 microM fendiline appeared to be independent of IP(3) because the [Ca(2+)](i) increase was unaltered by inhibiting phospholipase C with 2 microM U73122. Collectively, the results suggest that in MG63 cells fendiline caused an increase in [Ca(2+)](i) by inducing Ca(2+) influx and Ca(2+) release in an IP(3)-independent manner.
Wang
J
J
Department of Physical Medicine and Rehabilitation, Kaohsiung Veterans General Hospital, 386 Ta Chung 1st Rd., 813, Kaohsiung, Taiwan.
Cheng
J
J
Chan
R
R
Tseng
L
L
Chou
K
K
Tang
K
K
Chung Lee
K
K
Lo
Y
Y
Wang
J
J
Jan
C
C
D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D005275:Fendiline / Q000494:pharmacology*; D016257:Fura-2 / Q000494:pharmacology; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D002273:Carcinogens; D002614:Chelating Agents; D019284:Thapsigargin; D014700:Verapamil; D005275:Fendiline; D002118:Calcium; D016257:Fura-2