Woolcott Orison O, Gustafsson Amanda J, Dzabic Mensur, Pierro Cristina, Tedeschi Patrizia, Sandgren Johanna, Bari M Rizuanul, Nguyen K Hoa, Bianchi Marta, Rakonjac Marija, Rådmark Olof, Ostenson Claes-Göran, Islam Md Shahidul
Karolinska Institutet, Södersjukhuset, Department of Internal Medicine, Research Center, SE-118 83 Stockholm, Sweden.
Cell Calcium. 2006 Jun;39(6):529-37. doi: 10.1016/j.ceca.2006.02.003. Epub 2006 Apr 18.
Pancreatic beta-cells have ryanodine receptors but little is known about their physiological regulation. Previous studies have shown that arachidonic acid releases Ca(2+) from intracellular stores in beta-cells but the identity of the channels involved in the Ca(2+) release has not been elucidated. We studied the mechanism by which arachidonic acid induces Ca(2+) concentration changes in pancreatic beta-cells. Cytosolic free Ca(2+) concentration was measured in fura-2-loaded INS-1E cells and in primary beta-cells from Wistar rats. The increase of cytosolic Ca(2+) concentration induced by arachidonic acid (150microM) was due to both Ca(2+) release from intracellular stores and influx of Ca(2+) from extracellular medium. 5,8,11,14-Eicosatetraynoic acid, a non-metabolizable analogue of arachidonic acid, mimicked the effect of arachidonic acid, indicating that arachidonic acid itself mediated Ca(2+) increase. The Ca(2+) release induced by arachidonic acid was from the endoplasmic reticulum since it was blocked by thapsigargin. 2-Aminoethyl diphenylborinate (50microM), which is known to inhibit 1,4,5-inositol-triphosphate-receptors, did not block Ca(2+) release by arachidonic acid. However, ryanodine (100microM), a blocker of ryanodine receptors, abolished the effect of arachidonic acid on Ca(2+) release in both types of cells. These observations indicate that arachidonic acid is a physiological activator of ryanodine receptors in beta-cells.
胰腺β细胞具有ryanodine受体，但对其生理调节知之甚少。先前的研究表明，花生四烯酸可从β细胞的细胞内储存库释放Ca(2+)，但参与Ca(2+)释放的通道的身份尚未阐明。我们研究了花生四烯酸诱导胰腺β细胞中Ca(2+)浓度变化的机制。在装载fura-2的INS-1E细胞和来自Wistar大鼠的原代β细胞中测量细胞溶质游离Ca(2+)浓度。花生四烯酸（150μM）诱导的细胞溶质Ca(2+)浓度增加是由于细胞内储存库释放Ca(2+)以及细胞外介质中Ca(2+)的流入。5,8,11,14-二十碳四烯酸，一种花生四烯酸的不可代谢类似物，模拟了花生四烯酸的作用，表明花生四烯酸本身介导了Ca(2+)的增加。花生四烯酸诱导的Ca(2+)释放来自内质网，因为它被毒胡萝卜素阻断。已知可抑制1,4,5-肌醇三磷酸受体的2-氨基乙基二苯基硼酸酯（50μM）并未阻断花生四烯酸引起的Ca(2+)释放。然而，ryanodine受体的阻断剂ryanodine（100μM）消除了花生四烯酸对两种类型细胞中Ca(2+)释放的影响。这些观察结果表明，花生四烯酸是β细胞中ryanodine受体的生理激活剂。
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