Effect of the antidepressant desipramine on cytosolic Ca(2+) movement and proliferation in human osteosarcoma cells.
In human osteosarcoma MG63 cells, the effect of desipramine, an antidepressant, on intracellular Ca(2+) concentration ([Ca(2+)](i)) was measured by using fura-2. Desipramine (>10 micromol/l) caused a rapid and sustained rise of [Ca(2+)](i) in a concentration-dependent manner (EC(50) = 200 micromol/l). Desipramine-induced [Ca(2+)](i) rise was prevented by 80% 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 desipramine on [Ca(2+)](i) was abolished; also, pretreatment with desipramine partly reduced thapsigargin-induced [Ca(2+)](i) increase. U73122, an inhibitor of phospholipase C, did not affect desipramine-induced [Ca(2+)](i) rise. Overnight incubation with 10 micromol/l desipramine did not alter cell proliferation, but killed 32 and 89% of cells at concentrations of 100 and 200 micromol/l, respectively. These findings suggest that desipramine rapidly increases [Ca(2+)](i) in osteoblasts by stimulating both extracellular Ca(2+) influx and intracellular Ca(2+) release, and is cytotoxic at high concentrations.
Jan
Chung-Ren
CR
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan/ROC.
Lu
Yih-Chau
YC
Tseng
Li-Ling
LL
Jiann
Bang-Ping
BP
Chang
Hong-Tai
HT
Wang
Jue-Long
JL
Chen
Wei-Chuan
WC
Huang
Jong-Khing
JK
D000928:Antidepressive Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D016257:Fura-2; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology*
D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D019284:Thapsigargin; D010738:Type C Phospholipases; D002118:Calcium; D003891:Desipramine; D016257:Fura-2