Abstract
In Madin-Darby canine kidney (MDCK) cells, the effect of maprotiline, an antidepressant, on intracellular Ca2+ concentration ([Ca 2+]i) was measured using fura-2. Maprotiline (> 2.5 μM) caused a rapid rise of [Ca2+]i in a concentration-dependent manner (EC50 200 μM). 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 Mn 2+ 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 μM maprotiline enhanced cell viability, but 20-50 μM maprotiline decreased it. These findings suggest that maprotiline rapidly increases [Ca2+] i in renal tubular cells by stimulating both extracellular Ca 2+ influx and intracellular Ca2+ release, and may modulate cell proliferation in a concentration-dependent manner.
Original language | English |
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Pages (from-to) | 453-459 |
Number of pages | 7 |
Journal | Archives of Toxicology |
Volume | 78 |
Issue number | 8 |
DOIs | |
State | Published - 08 2004 |
Externally published | Yes |
Keywords
- Ca stores
- Fura-2
- MDCK cells
- Maprotiline
- Renal tubular cells