INTRACELLULAR CALCIUM STORE & SMOOTH MUSCLE CELL CA INDEPENDNT PHOSPHOLIPOASE A2

在这里，我们提出了多条证据来证明 体内钙储备的耗尽既是必要的，也是 足以激活钙非依赖性磷脂酶A2 精氨酸加压素(AVP)介导的花生四烯酸动员 A-10细胞中的酸性物质。第一，AVP诱导的[~3H]花生四烯酸 酸的释放与细胞内钙的增加无关，但 通过药物抑制钙离子的释放而减少 从内部商店买的。第二，他西格尔金导致了戏剧性的 A-10细胞释放[2H]花生四烯酸的速率与 AVP诱导花生四烯酸释放，以及AVP诱导花生四烯酸释放 AVP或thapsigargin完全抑制花生四烯酸 作者：(E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (贝尔)。A23187和thapsigargin也能诱导花生四烯酸释放。 同位素稀释物证实的胰岛β细胞 光谱，通过BEL敏感的机制。总而言之，这些 结果确定了一种新的范式，将钙的变化联系起来 钙调素调节细胞内环境的动态平衡 细胞内钙非依赖性磷脂酶A2的耗竭 钙库。

Herein we present multiple lines of evidence which demonstrate that depletion of internal calcium stores is both necessary and sufficient for the activation of calcium-independent phospholipase A2 during arginine vasopressin (AVP)-mediated mobilization of arachidonic acid in A-10 smooth muscle cells. First, AVP-induced [3H]arachidonic acid release was independent of increases in cytosolic calcium yet was decreased by pharmacological inhibition of the release of calcium ion from internal stores. Second, thapsigargin induced the dramatic release of [2H]arachidonic acid from A-10 cells at a similar rate as the AVP-induced release of arachidonic acid, and the release of arachidonic acid by either AVP or thapsigargin was entirely inhibited by (E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (BEL). A23187 and thapsigargin also induce arachidonate release from pancreatic islet beta cells, as demonstrated by isotope dilution mass spectrometry, by a BEL-sensitive mechanism. Collectively, these results identify a novel paradigm which links alterations in calcium homeostasis to the calmodulin-mediated regulation of calcium-independent phospholipase A2 through the depletion of internal calcium stores.