Triethyltin increases cytosolic Ca(2+) levels in human osteoblasts

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).