Role of Ca²⁺-independent phospholipase A₂ and cytochrome P-450 in store-operated calcium entry in 3T6 fibroblasts

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• 作者：Javier Martí ; nez and Juan J. Moreno
• 关键词：Calcium channels ; Capacitative calcium entry ; Epoxyeicosatrienoic acids ; Arachidonic acid ; Eicosanoids
• 刊名：Biochemical Pharmacology
• 出版年：2005
• 期刊代码：2_00062952
• 类别：pha
• 出版时间：2005
• 卷：70
• 期：5
• 页码：733-739
• 文件大小：238 K

摘要

Store-operated calcium (SOC) channels and capacitative Ca²⁺ entry play a key role in cellular functions, but their mechanism of activation remains unclear. Here, we show that thapsigargin induces [³H] arachidonic acid (AA) release, ⁴⁵Ca²⁺ influx and a subsequent enhancement of intracellular calcium concentration ([Ca²⁺]_i. Thapsigargin-induced elevation of [Ca²⁺]_i was inhibited by cytochrome P-450 inhibitors and by cytochrome P-450 epoxygenase inhibitor and was reverted by 11,12 EET addition. However, cyclooxygenase and lipoxygenase inhibitors have no effect. Moreover, we observed that four EETs were able to induce ⁴⁵Ca²⁺ influx. Finally, we reported that the effect of 11,12 EET on ⁴⁵Ca²⁺ influx was sensible to receptor-operated Ca²⁺ channel blockers (NiCl₂, LaCl₃) but not to voltage-dependent Ca²⁺ channel blocker as verapamil. Thus, AA released by Ca²⁺-independent phospholipase A₂ and AA metabolism through cytochrome P-450 pathway may be crucial molecular determinant in thapsigargin activation of SOC channels and store-operated Ca²⁺ entry pathway in 3T6 fibroblasts. Moreover, EETs, the main cytochrome P-450 epoxygenase metabolites of AA, are involved in thapsigargin-stimulated Ca²⁺ influx. In summary, our results suggest that EETs are components of calcium influx factor(s).