title: Effect of timosaponin A-III, from Anemarrhenae asphodeloides Bunge (Liliaceae), on calcium mobilization in vascular endothelial and smooth muscle cells and on vascular tension.
abstract: The effects of timosaponin A-III (TA-III), from Rhizoma Anemarrhenae, on Ca(2+) mobilization in vascular endothelial cells and smooth muscle cells and on vascular tension have been explored. TA-III increased intracellular Ca(2+) concentrations ([Ca(2+)](i)) in endothelials cells at a concentration larger than 5 microM with an EC(50) of 15 microM, and increased [Ca(2+)](i) in smooth muscle cells at a concentration larger than 1 microM with an EC(50) of 8 microM. Within 5 min, the [Ca(2+)](i) signal was composed of a gradual rise, and the speed of rising depended on the concentration of TA-III. The [Ca(2+)](i) signal was abolished by removing extracellular Ca(2+) and was recovered after reintroduction of Ca(2+). The TA-III-induced [Ca(2+)](i) increases in smooth muscle cells were partly inhibited by 10 microM nifedipine or 50 microM La(3+), but was insensitive to 10 microM verapamil and diltiazem. TA-III (10-100 microM) inhibited 0.3 microM phenylephrine-induced vascular contraction, which was abolished by pretreatment with 100 microM N(omega)-nitro-L-arginine (L-NNA) or by denuding the aorta. TA-III also increased [Ca(2+)](i) in renal tubular cells with an EC(50) of 8 microM. Collectively, the results show for the first time that TA-III causes [Ca(2+)](i) increases in the vascular system. TA-III acted by causing Ca(2+) influx without releasing intracellular Ca(2+). TA-III induced relaxation of phenylephrine-induced vascular contraction via inducing release of nitric oxide from endothelial cells.
authors.affiliation: National Research Institute of Chinese Medicine, Taipei, Taiwan.
authors.forename: Guei Jane
authors.initials: GJ
authors.lastname: Wang
authors.forename: Lie Chwen
authors.initials: LC
authors.lastname: Lin
authors.forename: Chieh Fu
authors.initials: CF
authors.lastname: Chen
authors.forename: Jin Shiung
authors.initials: JS
authors.lastname: Cheng
authors.forename: Yuk Keung
authors.initials: YK
authors.lastname: Lo
authors.forename: Kang Ju
authors.initials: KJ
authors.lastname: Chou
authors.forename: Kam Chung
authors.initials: KC
authors.lastname: Lee
authors.forename: Chun Peng
authors.initials: CP
authors.lastname: Liu
authors.forename: Yu Yuan
authors.initials: YY
authors.lastname: Wu
authors.forename: Warren
authors.initials: W
authors.lastname: Su
authors.forename: Wei Chung
authors.initials: WC
authors.lastname: Chen
authors.forename: Chung Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019668:Liliaceae / Q000737:chemistry*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology
chemical_list: D012503:Saponins; D010656:Phenylephrine; D002118:Calcium