Effect of fluoxetine on intracellular Ca2+ levels in bladder female transitional carcinoma (BFTC) cells.
The effect of the antidepressant fluoxetine on Ca2+ signaling in cultured cells was largely unknown. The effect of various concentrations of fluoxetine on [Ca 2+] i in populations of bladder female transitional cancer (BFTC) cells was evaluated by using fura-2 as a Ca2+ probe. Fluoxetine increased [Ca 2+] i concentration dependently (20-100 microM) with an EC50 value of 30 microM. The response was inhibited by 50-60% on extracellular Ca2+ removal. In Ca2+ -free medium, pretreatment with 1 microM thapsigargin (an inhibitor of the endoplasmic reticulum Ca2+ pump) abolished 50 microM fluoxetine-induced Ca2+ release; whereas pretreatment with fluoxetine did not alter the thapsigargin-induced Ca2+ response. Addition of 3 mM Ca2+ increased [Ca 2+] i after pretreatment with 50 microM fluoxetine in Ca2+ -free medium, suggestive of fluoxetine-induced capacitative Ca2+ entry. Suppression of inositol 1,4,5-trisphosphate formation by 2 microM U73122 (a phospholipase C inhibitor) did not affect 50 microM fluoxetine-induced Ca2+ release. Collectively, this study shows that fluoxetine increased [Ca 2+] i in bladder cancer cells in a concentration-dependent fashion, by releasing Ca2+ from thapsigargin-sensitive Ca2+ stores in an IP3-independent manner, and by inducing Ca2+ influx from extracellular medium.
Tang
K Y
KY
Department of Psychiatry
Lu
T
T
Chang
C H
CH
Lo
Y K
YK
Cheng
J S
JS
Wang
J L
JL
Chang
H T
HT
Jan
C R
CR
D002118:Calcium / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D002118:Calcium; D004963:Estrenes; D005473:Fluoxetine; D007202:Indicators and Reagents; D015544:Inositol 1,4,5-Trisphosphate; D011760:Pyrrolidinones; D017367:Selective Serotonin Reuptake Inhibitors; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione