Effects of flouxetine on ATP-induced calcium signaling in PC12 cells

Yeo Min Lee, Hee Jung Kim, Sun Hwa Hong, Myung Jun Kim, Do Sik Min, Duck Joo Rhie, Myung Suk Kim, Yang Hyeok Jo, Sang June Hahn, Shin Hee Yoon

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Abstract

Fluoxetine, a widely used anti-depressant compound, has several additional effects, including blockade of voltage-gated ion channels. We examined whether fluoxetine affects ATP-induced calcium signaling in PC12 cells by using fura-2-based digital calcium imaging and assay for [3H]-inositol phosphates (IPs). Treatment with ATP (100 μM for 2 min induced [Ca2+]i increases. The ATP-induced [Ca2+]i increases were significantly decreased by removal of extracellular Ca2+ and treatment with the inhibitor of endoplasmic reticulum Ca2+ ATPase thapsigargin (1 μM). Treatment with fluoxetine for 5 min blocked the ATP-induced [Ca2+]i increase concentration-dependently. Treatment with fluoxetine (30 μM) for 5 min blocked the ATP-induced [Ca2+]i increase following removal of extracellular Ca2+ and depletion of intracellular Ca2+ stores. While treatment with the L-type Ca2+ channel antagonist nimodipine for 10 min inhibited the ATP-induced [Ca2+]i increases significantly, treatment with fluoxetine alone blocked the ATP-induced responses. Treatment with fluoxetine also inhibited the 50 mM K+-induced [Ca2+]i increases completely. However, treatment with fluoxetine did not inhibit the ATP-induced [3H]-IPs formation. Collectively, we conclude that fluoxetine inhibits ATP-induced [Ca2+]i increases in PC12 cells by inhibiting both an influx of extracellular Ca2+ and a release of Ca2+ from intracellular stores without affecting IPs formation.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalKorean Journal of Physiology and Pharmacology
Volume8
Issue number1
Publication statusPublished - 2004 Feb 1

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology

Cite this

Lee, Y. M., Kim, H. J., Hong, S. H., Kim, M. J., Min, D. S., Rhie, D. J., Kim, M. S., Jo, Y. H., Hahn, S. J., & Yoon, S. H. (2004). Effects of flouxetine on ATP-induced calcium signaling in PC12 cells. Korean Journal of Physiology and Pharmacology, 8(1), 57-63.