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 c ells was largely unknown. The effect of various concentrations of fluoxetin e on [Ca2+](i) in populations of bladder female transitional cancer (BFTC) cells was evaluated by using fura-2 as a Ca2+ probe. Fluoxetine increased [ Ca2+]i concentration dependently (20-100 muM) with an EC50 value of 30 muM. The response was inhibited by 50-60% on extracellular Ca2+ removal. In Ca2 +-free medium, pretreatment with 1 muM thapsigargin tan inhibitor of the en doplasmic reticulum Ca2+ pump) abolished 50 muM fluoxetine-induced Ca2+ rel ease: whereas pretreatment with fluoxetine did not alter the thapsigargin-i nduced Ca2+ response. Addition of 3 mM Ca2+ increased [Ca2+](i) after pretr eatment with 50 muM fluoxetine in Ca2+-free medium, suggestive of fluoxetin e-induced capacitative Ca2+ entry. Suppression of inositol 1,4,5-trisphosph ate formation by 2 muM U73122 (a phospholipase C inhibitor) did not affect 50 muM fluoxetine-induced Ca2+ release. Collectively, this study shows that fluoxetine increased [Ca2+](i) in bladder cancer cells in a concentration- dependent fashion, by releasing Ca2+ from thapsigargin-sensitive Ca2+ store s in an IP3-independent manner, and by inducing Ca2+ influx from extracellu lar medium. (C) 2001 Academic Press.