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

Shu Shong Hsu, Wei Chung Chen, Bang Ping Jiann, Jin Shyr Chen, Jong Khing Huang, Hong Tai Chang, He Hsiung Cheng, Yuk Keung Lo, Chin Man Ho, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

3 Scopus citations

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 languageEnglish
Pages (from-to)453-459
Number of pages7
JournalArchives of Toxicology
Volume78
Issue number8
DOIs
StatePublished - 08 2004
Externally publishedYes

Keywords

  • Ca stores
  • Fura-2
  • MDCK cells
  • Maprotiline
  • Renal tubular cells

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