title: Tetrandrine blocks voltage-dependent calcium entry and inhibits the bradykinin-induced elevation of intracellular calcium in NG108-15 cells.
abstract: 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.
authors.affiliation: Abteilung Neurotoxikologie, Medizinisches Institut für Unwelthygiene an der Heinrich-Heine-Universität Düsseldorf, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Bickmeyer
authors.forename: M F
authors.initials: MF
authors.lastname: Hare
authors.forename: W D
authors.initials: WD
authors.lastname: Atchison
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D044182:Benzylisoquinolines; D001920:Bradykinin / Q000037:antagonists & inhibitors*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D016257:Fura-2; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; C009438:tetrandrine; D009543:Nifedipine; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2