Effect of NPC-14686 (FMOC-L-HOMOPHENYLALANINE (cas 132684-59-4)) on intracellular Ca2+ levels in human hepatoma cells

Add time:08/24/2019    Source:sciencedirect.com

The effect of NPC-14686, a potential anti-inflammatory drug, on cytosolic free Ca2+ levels ([Ca2+]i) in HA22/VGH human hepatoma cells was explored by using fura-2 as a fluorescent Ca2+ indicator. NPC-14686 at concentrations above 10 μM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 100 μM. The Ca2+ signal was reduced by removing extracellular Ca2+ or by 10 μM nifedipine and was not changed by verapamil or diltiazem. Pretreatment with 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) to deplete the endoplasmic reticulum Ca2+ abolished 200 μM NPC-14686-induced Ca2+ release; and conversely pretreatment with NPC-14686 abolished thapsigargin-induced Ca2+ release. The Ca2+ release induced by 200 μM NPC-14686 was not changed by inhibiting phospholipase C with 2 μM U73122. Together, the results suggest that in human hepatoma cells, NPC-14686 induced a [Ca2+]i increase by causing store Ca2+ release from the endoplasmic reticulum in an phospholipase C-independent manner, and by inducing nifedipine-sensitive Ca2+ influx.

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