Effect of the antidepressant desipramine on cytosolic Ca2+ movement and proliferation in human osteosarcoma cells

In human osteosarcoma MG63 cells, the effect of desipramine, an antidepressant, on intracellular Ca2+ concentration ([Ca2+](i)) was measured by using fura-2. Desipramine (>10 mumol/l) caused a rapid and sustained rise of [Ca2+](i) in a concentration-dependent manner (EC50 = 200 mumol/l). Desipramine- induced [Ca2+](i) rise was prevented by 80% by removal of extracellular Ca2+ but was not altered by voltage-gated Ca2+ channel blockers. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum (ER) Ca2+-ATPase, caused a monophasic [Ca2+](i) rise, after which the increasing effect of desipramine on [Ca2+](i) was abolished; also, pretreatment with desipramine partly reduced thapsigargin-induced [Ca2+](i) increase. U73122, an inhibitor of phospholipase C, did not affect desipramine-induced [Ca2+](i) rise. Overnight incubation with 10 mumol/l desipramine did not alter cell proliferation, but killed 32 and 89% of cells at concentrations of 100 and 200 mumol/l, respectively. These findings suggest that desipramine rapidly increases [Ca2+](i) in osteoblasts by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release, and is cytotoxic at high concentrations. Copyright (C) 2003 S. Karger AG, Basel.