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

• 영문명: Efffects of Fluoxetine on ATP-induced Calcium Signaling in PC12 Cells
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Yeo-Min Lee Hee Jung Kim Sun Hwa Hong Myung-Jun Kim Do Sik Min Duck-Joo
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제8권 제1호, 57~63쪽, 전체 7쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2004.01.01

영문 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 (100μM) 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 (1μM). Treatment with fluoxetine for 5 min blocked the ATP-induced [Ca^2⁢]_i increase concentration-dependently. Treatment with fluoxetine (30μM) 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-induced [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

ATP Fluoxetine Inositol phosphates Non-selective cation channels PC12 cells,