Effect of desipramine on Ca²⁺ levels and growth in renal tubular cells

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• 作者：Ho ; Chin-Man ; Kuo ; Soong-Yu ; Chen ; Ching-Hsein ; Huang ; Jong-Khing ; Jan ; Chung-Ren
• 关键词：Ca²⁺ signaling ; Desipramine ; Fura-2 ; MDCK cells ; Renal tubular ; Thapsigargin
• 刊名：Cellular Signalling
• 出版年：2005
• 出版时间：July, 2005
• 年：2005
• 卷：17
• 期：7
• 页码：837-845
• 全文大小：440 K

文摘

The in vitro effect of desipramine on renal tubular cell is unknown. In Madin–Darby canine kidney (MDCK) cells, the effect of desipramine on intracellular Ca²⁺ concentration ([Ca²⁺]_i) was measured by using fura-2. Desipramine (>25 μM) caused a rapid and sustained rise of [Ca²⁺]_i in a concentration-dependent manner (EC₅₀=50 μM). Desipramine-induced [Ca²⁺]_i rise was prevented by 40 % by removal of extracellular Ca²⁺ but was not altered by L-type Ca²⁺ channel blockers. In Ca²⁺-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca²⁺-ATPase, caused a monophasic [Ca²⁺]_i rise, after which desipramine failed to release more Ca²⁺; in addition, pretreatment with desipramine partly decreased thapsigargin-induced [Ca²⁺]_i increase. U73122, an inhibitor of phospholipase C, did not change desipramine-induced [Ca²⁺]_i rise. Incubation with 10–100 μM desipramine enhances or inhibits cell proliferation in a concentration- and time-dependent manner. The inhibitory effect of desipramine on proliferation was not extracellular Ca²⁺-dependent. Apoptosis appears to contribute to desipramine-induced cell death. Together, these findings suggest that desipramine increases baseline [Ca²⁺]_i in renal tubular cells by evoking both extracellular Ca²⁺ influx and intracellular Ca²⁺ release, and can cause apoptosis.