Calmidazolium-induced rises in cytosolic calcium concentrations in Madin Darby canine kidney cells

Chung Ren Jan*, Ching Jiunn Tseng

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

27 Scopus citations

Abstract

The effect of calmidazolium on Ca2+ signaling in Madin Darby canine kidney (MDCK) cells was investigated using fura-2 as a Ca2+ probe. Calmidazolium at 2-5 μM increased [Ca2+](i) concentration dependently. The [Ca2+](i) rise induced by 2-5 μM calmidazolium comprised an immediate rise and a slow decay. External Ca2+ removal partly inhibited the Ca2+ signals, suggesting that calmidazolium activated external Ca2+ influx and internal Ca2+ release. In Ca2+-free medium, pretreatment with 3 μM calmidazolium abolished the Ca2+ release induced by 1 μM thapsigargin, an endoplasmic reticulum Ca2+ pump inhibitor, and, vice versa, pretreatment with thapsigargin inhibited calmidazolium-induced Ca2+ release. This indicates that thapsigargin-sensitive Ca2+ store was the source of calmidazolium-induced Ca2+ release. Calmidazolium (3 μM) induced Mn2+ quench of fura-2 fluorescence at 360 nm excitation wavelength, which was suppressed by 0.1 mM La3+. Addition of 3 mM Ca2+ increased [Ca2+](i) after pretreatment with 3-5 μM calmidazolium in Ca2+-free medium. This implies that calmidazolium activated concentration-dependent capacitative Ca2+ entry. Calmidazolium (3 μM) augmented the capacitative Ca2+ entry induced by 1 μM thapsigargin or 0.1 mM ATP by 38%. Calmidazolium (3 μM)- induced Ca2+ release was blocked by pretreatment with 40 μM aristolochic acid and 2 μM U73122 (2 μM) to inhibit phospholipase A2 and phospholipase, respectively, but pretreatment with 0.1 mM propranolol to inhibit phospholipase D had no effect. This suggests that calmidazolium induced internal Ca2+ release in a manner dependent on phospholipases C- and A2- coupled events. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)142-150
Number of pages9
JournalToxicology and Applied Pharmacology
Volume162
Issue number2
DOIs
StatePublished - 15 01 2000
Externally publishedYes

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