Abstract
The effect of fluoxetine on Ca2+ signaling in Madin-Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca2+ probe. Fluoxetine increased [Ca2+]i concentration-dependently between 5 microM and 200 microM with an EC50 value of 40 microM. The response was reduced by external Ca2+ removal by 30%40%. In Ca2+-free medium pretreatment with 1 microM thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+ pump, abolished 100 microM fluoxetine-induced Ca2+ release. Addition of 3 mM Ca2+ to Ca2+-free medium increased [Ca2+]i when cells were pretreated with 100 microM fluoxetine. Suppression of 1,4,5-trisphosphate (IP3) formation by 2 microM U73122 (a phospholipase C inhibitor) did not affect 100 microM fluoxetine-induced Ca2+ release. Fluoxetine (5-100 microM) also increased [Ca2+]i in neutrophils, prostate cancer cells and bladder cancer cells from human and rat glioma cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / pharmacology
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Animals
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Calcium / metabolism*
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Calcium-Transporting ATPases / antagonists & inhibitors
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Calcium-Transporting ATPases / metabolism
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Cell Line
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Dogs
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Endoplasmic Reticulum / enzymology
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Estrenes / pharmacology
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Fluoxetine / pharmacology*
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Humans
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Inositol 1,4,5-Trisphosphate / metabolism
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Kidney / cytology
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Kidney / drug effects*
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Kidney / metabolism
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Neutrophils / cytology
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Neutrophils / drug effects
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Neutrophils / metabolism
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Pyrrolidinones / pharmacology
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Selective Serotonin Reuptake Inhibitors / pharmacology*
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Thapsigargin / pharmacology
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Time Factors
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Tumor Cells, Cultured
Substances
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Estrenes
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Pyrrolidinones
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Serotonin Uptake Inhibitors
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Fluoxetine
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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Thapsigargin
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Inositol 1,4,5-Trisphosphate
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Adenosine Triphosphate
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Calcium-Transporting ATPases
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Calcium