Neurotoxicology. 1996 Summer; 17(2): 335-41.

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

Bickmeyer U, Hare MF, Atchison WD.

Abteilung Neurotoxikologie, Medizinisches Institut f�r Unwelthygiene an der Heinrich-Heine-Universit�t D�sseldorf, Germany.

Tetrandrine, a plant alkaloid used in Chinese traditional medicine blocks voltage-dependent Ca2+ entry in NG108-15 cells as assessed using fura-2 microfluorimetry. Cells were depolarized with 50 mM KCI for one min resulting in a transient increase in the 340/380 nm ratio of fura 2 fluorescence, indicative of an increase in [Ca2+]i. Treatment of the same cell with 100 microM 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 [Ca2+] due to release of Ca2+ from intracellular stores via activation of the inositol trisphosphate (IP3) second messenger system. After pre-treatment with 100 microM tetrandrine for seven min, the Bk (1 microM, 1 min) response was significantly reduced. Likewise, the effect of angiotensin II (AT-II), which also causes an IP3 dependent release of Ca2+ from intracellular stores, was ablated by tetrandrine. Thus, in addition to block of voltage-dependent Ca2+ channels, tetrandrine also caused disturbances in intracellular Ca2+ signalling.