The anti-anginal drug fendiline increases intracellular Ca2+ levels in MG63 human osteosarcoma cells

The effect of fendiline, an anti-anginal drug, on cytosolic free Ca2+ level s ([Ca2+](i)) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca2+ indicator. Fendiline at concentrations between 1 and 200 muM inc reased [Ca2+](i) in a concentration-dependent manner and the signal saturat ed at 100 muM. The Ca2+ signal was inhibited by 65 +/- 5% by Ca2+ removal a nd by 38 +/- 5% by 10 muM nifedipine, but was unchanged by 10 muM La3+ or v erapamil. In Ca2+-free medium, pre-treatment with 1 muM thapsigargin tan en doplasmic reticulum Ca2+ pump inhibitor) to deplete the endoplasmic reticul um Ca2+ store inhibited fendiline-induced intracellular Ca2+ release. The C a2+ release induced by 50 muM fendiline appeared to be independent of IP3 b ecause the [Ca2+](i) increase was unaltered by inhibiting phospholipase C w ith 2 muM U73122. Collectively, the results suggest that in MG63 cells fend iline caused an increase in [Ca2+](i) by inducing Ca2+ influx and Ca2+ rele ase in an IP3-independent manner. (C) 2001 Elsevier Science Ireland Ltd. Al l rights reserved.