Tetrandrine blocks voltage-dependent calcium entry and inhibits the bradykinin-induced elevation of intracellular calcium in NG108-15 cells

Tetrandrine, a plant alkaloid used in Chinese traditional medicine blocks voltage-dependent Ca 2+ entry in NG108-15 cells as assessed using fura-2 microfluorimetry. Cells were depolarized with 50 mM KCl for one min resulting in a transient increase in the 340/380 nm ratio of fura-2 fluorescence, indicative of an increase in (ca 2+ ) i . Treatment of the same cell with 100 μM tetrandrine for seven min followed by an identical K + depolarization blocked the increase in 340/380 nm fluorescence ratio. Washing with tetrandrine-free solutions for 20 min partially reversed this effect. Bradykinin (Bk) induces transient and repetitive increases in [Ca 2+ ] i due to release of ca 2+ from intracellular stores via activation ofthe inositol trisphosphate (IP 3 ) second messenger system. After pre-treatment with 100μM tetrandrine for seven min, the Bk (1 μM, 1 min) response was significantly reduced. Likewise, the effect of angiotensin II (AT- II), which also causes an IP 3 -dependent release of Ca 2+ from intracellular stores, was ablated by tetrandrine. Thus, in addition to block of voltage-dependent Ca 2+ channels, tetrandrine also caused disturbances in intracellular Ca 2+ signalling.