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 Ca2mobilization were studied in rat glioma C6 cells. TET and HER alone di d not affect the resting cytoplasmic Ca2+ concentration ([Ca2+](i)). T ET and HER inhibited the peak and sustained elevation of [Ca2+](i) ind uced by bombesin and thapsigargin (TG), a microsomal Ca2+ ATPase inhib itor, in a dose-dependent manner. The doses of TET or HER needed to ab olish the sustained and peak increase in [Ca2+](i) induced by bombesin and TG were 30 mu M and 300 mu M, respectively. TET and HER did not i ncrease 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 intra cellular stores induced by bombesin and TG. In the absence of extracel lular 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. TE T and HER did not affect this leakage entry of Ca2+. The present resul ts suggest that TET and HER inhibit Ca2+ release from intracellular st ores as well as Ca2+ entry from extracellular medium evoked by bombesi n and TG. In addition, TET and HER inhibit IP3 accumulation induced by bombesin in rat glioma C6 cells.