Efffects of Fluoxetine on ATP-induced Calcium Signaling in PC12 Cells.
- Author:
Yeo Min LEE
1
;
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
Author Information
1. Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea. s-hyoon@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
ATP;
Fluoxetine;
Inositol phosphates;
Non-selective cation channels;
PC12 cells;
Voltage- gated Ca2+ channels
- MeSH:
Adenosine Triphosphate;
Animals;
Calcium Signaling*;
Calcium*;
Calcium-Transporting ATPases;
Endoplasmic Reticulum;
Fluoxetine*;
Inositol Phosphates;
Ion Channels;
Nimodipine;
PC12 Cells*;
Phosphates;
Thapsigargin
- From:The Korean Journal of Physiology and Pharmacology
2004;8(1):57-63
- CountryRepublic of Korea
- Language:English
-
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 (100microM) 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 (1microM). Treatment with fluoxetine for 5 min blocked the ATP-induced [Ca2+]i increase concentration-dependently. Treatment with fluoxetine (30microM) 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.
