title: Triethyltin increases cytosolic Ca(2+) levels in human osteoblasts.
abstract: In human osteosarcoma MG63 cells, effect of triethyltin, an environmental toxicant, on intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured by using fura-2. Triethyltin (1-50 μM) caused a rapid and sustained plateau rise of [Ca(2+)](i) in a concentration-dependent manner (EC(50)=10 μM). Triethyltin-induced [Ca(2+)](i) rise was prevented by 50% by removal of extracellular Ca(2+) but was not altered by voltage-gated Ca(2+) channel blockers. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum (ER) Ca(2+)-ATPase, caused a monophasic [Ca(2+)](i) rise, after which the increasing effect of triethyltin on [Ca(2+)](i) was attenuated by 60%; also, pretreatment with triethyltin abolished thapsigargin-induced [Ca(2+)](i) increase. Depletion of mitochondrial Ca(2+) with carbonylcyanide m-chlorophenylhydrazone (CCCP; 2 μM) did not affect triethyltin-induced Ca(2+) release. U73122, an inhibitor of phoispholipase C, abolished ATP (but not triethyltin)-induced [Ca(2+)](i) rise. A low concentration (1 μM) of triethyltin failed to alter ATP and bradykinin-induced [Ca(2+)](i) rises. These findings suggest that triethyltin rapidly increases [Ca(2+)](i) in osteoblasts by stimulating both extracellular Ca(2+) influx and intracellular Ca(2+) release via as yet unidentified mechanism(s).
authors.affiliation: Department of Orthopaedic Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, ROC.
authors.forename: Yih-Chau
authors.initials: YC
authors.lastname: Lu
authors.forename: Soong-Yu
authors.initials: SY
authors.lastname: Kuo
authors.forename: Bang-Ping
authors.initials: BP
authors.lastname: Jiann
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Wei-Chung
authors.initials: WC
authors.lastname: Chen
authors.forename: Jong-Khing
authors.initials: JK
authors.lastname: Huang
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan