Effect of the antidepressant maprotiline on calcium movement and the viability of renal tubular cells

In Madin-Darby canine kidney (MDCK) cells, the effect of maprotiline, an antidepressant, on intracellular Ca2+ concentration ([Ca2+](i)) was measured using fura-2. Maprotiline (>2.5 muM) caused a rapid rise of [Ca2+](i) in a concentration-dependent manner (EC50 200 muM). Maprotiline-induced [Ca2+](i) rise was reduced by removal of extracellular Ca2+ or by addition of La3+, but was not altered by voltage-gated Ca2+-channel blockers. Maprotiline-induced Mn2+ influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca2+ influx. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-ATPase, caused a monophasic [Ca2+](i) rise, after which the increasing effect of maprotiline on [Ca2+](i) was nearly abolished; also, pretreatment with maprotiline reduced a portion of thapsigargin-induced [Ca2+](i) rise. U73122, an inhibitor of phospholipase C, abolished [Ca2+](i) rise induced by ATP (but not by maprotiline). Overnight incubation with 1-10 muM maprotiline enhanced cell viability, but 20-50 muM maprotiline decreased it. These findings suggest that maprotiline rapidly increases [Ca2+](i) in renal tubular cells by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release, and may modulate cell proliferation in a concentration-dependent manner.