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 Ca(2+) concentration ([Ca(2+)](i)) was measured using fura-2. Maprotiline (> 2.5 microM) caused a rapid rise of [Ca(2+)](i) in a concentration-dependent manner (EC(50) 200 microM). Maprotiline-induced [Ca(2+)](i) rise was reduced by removal of extracellular Ca(2+) or by addition of La(3+), but was not altered by voltage-gated Ca(2+)-channel blockers. Maprotiline-induced Mn(2+) influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca(2+) influx. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic [Ca(2+)](i) rise, after which the increasing effect of maprotiline on [Ca(2+)](i) was nearly abolished; also, pretreatment with maprotiline reduced a portion of thapsigargin-induced [Ca(2+)](i) rise. U73122, an inhibitor of phospholipase C, abolished [Ca(2+)](i) rise induced by ATP (but not by maprotiline). Overnight incubation with 1-10 microM maprotiline enhanced cell viability, but 20-50 microM maprotiline decreased it. These findings suggest that maprotiline rapidly increases [Ca(2+)](i) in renal tubular cells by stimulating both extracellular Ca(2+) influx and intracellular Ca(2+) release, and may modulate cell proliferation in a concentration-dependent manner.
Hsu
Shu-Shong
SS
Department of Surgery, Kaohsiung Veterans General Hospital, 813 Kaohsiung, Taiwan.
Chen
Wei-Chung
WC
Jiann
Bang-Ping
BP
Chen
Jin-Shyr
JS
Huang
Jong-Khing
JK
Chang
Hong-Tai
HT
Cheng
He-Hsiung
HH
Lo
Yuk-Keung
YK
Ho
Chin-Man
CM
Jan
Chung-Ren
CR
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008376:Maprotiline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D018687:Antidepressive Agents, Second-Generation; D004791:Enzyme Inhibitors; D004963:Estrenes; D005456:Fluorescent Dyes; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D008376:Maprotiline; D019284:Thapsigargin; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2