Inhibitory effects of tetrandrine and hernandezine on Ca2+ mobilization in rat glioma C6 cells.

The effects of tetrandrine (TET), a Ca2+ antagonist of Chinese herbal origin, and hernandezine (HER), a structural analogue of TET, on Ca2+ mobilization were studied in rat glioma C6 cells. TET and HER alone did not affect the resting cytoplasmic Ca2+ concentration ([Ca2+]i). TET and HER inhibited the peak and sustained elevation of [Ca2+]i induced by bombesin and thapsigargin (TG), a microsomal Ca2+ ATPase inhibitor, in a dose-dependent manner. The doses of TET or HER needed to abolish the sustained and peak increase in [Ca2+]i induced by bombesin and TG were 30 microM and 300 microM, respectively. TET and HER did not increase inositol 1,4,5-trisphosphate (IP3) accumulation by themselves but inhibited IP3 accumulation elevated by bombesin. In permeabilized C6 cells, the addition of IP3 and TG released Ca2+ from intracellular stores. Pretreatment with TET or HER abolished Ca2+ release from intracellular stores induced by bombesin and TG. In the absence of extracellular Ca2+, the addition of 3 mM Ca2+ to extracellular medium slightly increased [Ca2+]i, which indicated Ca2+ entry due to leakage of Ca2+ at the plasma membrane but not Ca2+ influx through Ca2+ channels. TET and HER did not affect this leakage entry of Ca2+. The present results suggest that TET and HER inhibit Ca2+ release from intracellular stores as well as Ca2+ entry from extracellular medium evoked by bombesin and TG. In addition, TET and HER inhibit IP3 accumulation induced by bombesin in rat glioma C6 cells.