Effect of desipramine on Ca²⁺ levels and growth in renal tubular cells

The in vitro effect of desipramine on renal tubular cell is unknown. In Madin-Darby canine kidney (MDCK) cells, the effect of desipramine on intracellular Ca²⁺ concentration ([Ca²⁺]_i) was measured by using fura-2. Desipramine (>25 μM) caused a rapid and sustained rise of [Ca²⁺]_i in a concentration-dependent manner (EC₅₀=50 μM). Desipramine-induced [Ca²⁺] _i rise was prevented by 40% by removal of extracellular Ca ²⁺ but was not altered by L-type Ca²⁺ channel blockers. In Ca²⁺-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca²⁺-ATPase, caused a monophasic [Ca²⁺] _i rise, after which desipramine failed to release more Ca ²⁺; in addition, pretreatment with desipramine partly decreased thapsigargin-induced [Ca²⁺]_i increase. U73122, an inhibitor of phospholipase C, did not change desipramine-induced [Ca ²⁺]_i rise. Incubation with 10-100 μM desipramine enhances or inhibits cell proliferation in a concentration- and time-dependent manner. The inhibitory effect of desipramine on proliferation was not extracellular Ca²⁺-dependent. Apoptosis appears to contribute to desipramine-induced cell death. Together, these findings suggest that desipramine increases baseline [Ca²⁺]_i in renal tubular cells by evoking both extracellular Ca²⁺ influx and intracellular Ca²⁺ release, and can cause apoptosis.