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

• Published in: Archives of toxicology 2004-08, Vol.78 (8), p.453-459
• Main Authors: HSU, Shu-Shong, CHEN, Wei-Chung, JIANN, Bang-Ping, CHEN, Jin-Shyr, HUANG, Jong-Khing, CHANG, Hong-Tai, CHENG, He-Hsiung, LO, Yuk-Keung, HO, Chin-Man, JAN, Chung-Ren
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive Agents, Second-Generation - pharmacology; Biological and medical sciences; Calcium - metabolism; Calcium Signaling - drug effects; Cell Line; Cell Survival - drug effects; Dogs; Drug toxicity and drugs side effects treatment; Enzyme Inhibitors - pharmacology; Estrenes - pharmacology; Fluorescent Dyes; Fura-2; Kidney Tubules - cytology; Kidney Tubules - drug effects; Kidney Tubules - metabolism; Maprotiline - pharmacology; Medical sciences; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - pharmacology; Proteins; Pyrrolidinones - pharmacology; Thapsigargin - pharmacology; Toxicity: urogenital system; Type C Phospholipases - antagonists & inhibitors; Type C Phospholipases - metabolism
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-004-0564-1

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.