The anti-anginal drug Fendiline (cas 13042-18-7) increases intracellular Ca2+ levels in MG63 human osteosarcoma cells

Add time:09/24/2019    Source:sciencedirect.com

The effect of Fendiline (cas 13042-18-7), an anti-anginal drug, on cytosolic free Ca2+ levels ([Ca2+]i) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca2+ indicator. Fendiline at concentrations between 1 and 200 μM increased [Ca2+]i in a concentration-dependent manner and the signal saturated at 100 μM. The Ca2+ signal was inhibited by 65±5% by Ca2+ removal and by 38±5% by 10 μM nifedipine, but was unchanged by 10 μM La3+ or verapamil. In Ca2+-free medium, pre-treatment with 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete the endoplasmic reticulum Ca2+ store inhibited fendiline-induced intracellular Ca2+ release. The Ca2+ release induced by 50 μM fendiline appeared to be independent of IP3 because the [Ca2+]i increase was unaltered by inhibiting phospholipase C with 2 μM U73122. Collectively, the results suggest that in MG63 cells fendiline caused an increase in [Ca2+]i by inducing Ca2+ influx and Ca2+ release in an IP3-independent manner.

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