Effect of nordihydroguaiaretic acid on intracellular Ca2+ concentrations in C6 glioma cells

The effect of nordihydroguaiaretic acid (NDGA) on Ca2+ signaling in C6 glioma cells has been investigated. NDGA (5-100 muM) increased [Ca2+](i) concentration-dependently. The [Ca2+](i) increase comprised an initial rise and an elevated phase over a time period of 4 min. Removal of extracellular Ca2+ reduced NDGA-induced [Ca2+](i) signals by 52 +/- 2%. After incubation of cells with NDGA in Ca2+-free medium for 4 min, addition of 3 mM CaCl2 induced a concentration-dependent increase in [Ca2+](i). NDGA (100 muM)-induced [Ca2+](i) increases in Ca2+-containing medium was not changed by pretreatment with 10 muM nifedipine or verapamil. In Ca2+-free medium. pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (1 muM) abolished 100 muM NDGA-induced [Ca2+](i) increases. Inhibition of phospholipase C with 2 muM U73122 had little effect on 100 muM NDGA-induced Ca2+ release. Several other lipoxygenase inhibitors had no effect on basal [Ca2+](i). Collectively, the results suggest that NDGA increased [Ca2+](i) in glioma cells in a lipoxygenase-independent manner, by releasing Ca2+ from the endoplasmic reticulum in a manner independent of phospholipase C activity and by causing Ca2+ influx. (C) 2002 Elsevier Science Ltd. All rights reserved.