Ausiello D A, Zusman R M
Biochem J. 1984 May 15;220(1):139-45. doi: 10.1042/bj2200139.
The role of Ca2+ in the stimulation of prostaglandin (PG) biosynthesis by vasopressin was investigated in rabbit renal-medullary interstitial cells in tissue culture. A decrease in extracellular Ca2+ to less than 25 microM did not affect basal PGE2 production, but inhibited PGE2 synthesis stimulated by vasopressin, angiotensin and the Ca2+ ionophore A23187 by 55, 65 and 95% respectively. The study of vasopressin-stimulated PGE2 synthesis in the absence of extracellular Ca2+ demonstrated that: (a) hormone-sensitive phospholipase activity was inhibited as measured by [3H]arachidonic acid release; (b) the maximal rate of vasopressin-stimulated activity was decreased without a change in the vasopressin concentration that evoked half-maximal stimulation of PGE2 synthesis; and (c) the Ca2+-channel blocker verapamil and the Ca2+-calmodulin antagonist trifluoperazine mimicked the inhibitory effects of removing extracellular Ca2+. These agents had no effect in the absence of Ca2+. In contrast with their effects on vasopressin action, neither the removal of extracellular Ca2+ nor the addition of verapamil altered the ability of hyperosmotic mannitol to increase PGE2 synthesis. These data are consistent with the hypothesis that a component of vasopressin-stimulated PGE2 biosynthesis involves the influx of extracellular Ca2+, followed by the activation of Ca2+-calmodulin-stimulated phospholipase(s).
通过组织培养的兔肾髓质间质细胞，研究了钙离子在血管加压素刺激前列腺素（PG）生物合成中的作用。细胞外钙离子浓度降至低于25微摩尔/升时，不影响基础前列腺素E2的产生，但分别抑制血管加压素、血管紧张素和钙离子载体A23187刺激的前列腺素E2合成55%、65%和95%。在无细胞外钙离子的情况下对血管加压素刺激的前列腺素E2合成进行研究，结果表明：（a）通过[3H]花生四烯酸释放测定，激素敏感的磷脂酶活性受到抑制；（b）血管加压素刺激活性的最大速率降低，而引起前列腺素E2合成半最大刺激的血管加压素浓度未发生变化；（c）钙离子通道阻滞剂维拉帕米和钙离子-钙调蛋白拮抗剂三氟拉嗪模拟了去除细胞外钙离子的抑制作用。在无钙离子的情况下，这些药物无作用。与它们对血管加压素作用的影响相反，去除细胞外钙离子或添加维拉帕米均未改变高渗甘露醇增加前列腺素E2合成的能力。这些数据与以下假设一致，即血管加压素刺激的前列腺素E2生物合成的一个组成部分涉及细胞外钙离子的内流，随后是钙离子-钙调蛋白刺激的磷脂酶的激活。
