Effects of Fluoxetine on ATP-induced Calcium Signaling in PC12 Cells

  • Lee, Yeo-Min (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Kim, Hee-Jung (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Hong, Sun-Hwa (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Kim, Myung-Jun (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Min, Do-Sik (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Rhie, Duck-Joo (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Kim, Myung-Suk (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Jo, Yang-Hyeok (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Hahn, Sang-June (Department of Physiology, College of Medicine, The Catholic University of Korea) ;
  • Yoon, Shin-Hee (Department of Physiology, College of Medicine, The Catholic University of Korea)
  • 발행 : 2004.02.21

초록

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 $(100\;{\mu}M)$ for 2 min induced $[Ca^{2+}]_i$ increases. The ATP-induced $[Ca^{2+}]_i$ increases were significantly decreased by removal of extracellular $Ca^{2+}$ and treatment with the inhibitor of endoplasmic reticulum $Ca^{2+}$ ATPase thapsigargin $(1\;{\mu}M)$. Treatment with fluoxetine for 5 min blocked the ATP-induced $[Ca^{2+}]_i$ increase concentration-dependently. Treatment with fluoxetine $(30\;{\mu}M)$ for 5 min blocked the ATP-induced $[Ca^{2+}]_i$ increase following removal of extracellular $Ca^{2+}$ and depletion of intracellular $Ca^{2+}$ stores. While treatment with the L-type $Ca^{2+}$ channel antagonist nimodipine for 10 min inhibited the ATP-induced $[Ca^{2+}]_i$ increases significantly, treatment with fluoxetine alone blocked the ATP-induced responses. Treatment with fluoxetine also inhibited the 50 mM $K^+-induced$ $[Ca^{2+}]_i$ increases completely. However, treatment with fluoxetine did not inhibit the ATP-induced $[^3H]-IPs$ formation. Collectively, we conclude that fluoxetine inhibits ATP-indueed $[Ca^{2+}]_i$ increases in PC12 cells by inhibiting both an influx of extracellular $Ca^{2+}$ and a release of $Ca^{2+}$ from intracellular stores without affecting IPs formation.

키워드

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