Kojima I, Kojima K, Rasmussen H
J Biol Chem. 1985 Aug 5;260(16):9177-84.
When angiotensin II stimulates aldosterone secretion, it causes a rapid but transient mobilization of calcium from an intracellular pool and a sustained increase in the influx of calcium in adrenal glomerulosa cells. The present studies were undertaken to determine the respective roles of the two angiotensin II-induced changes in cellular calcium metabolism in modulating events during the sustained phase of cellular response which is thought to be mediated by the C-kinase branch of the calcium messenger system. The sustained response to angiotensin II is only 50% of maximal in cells pretreated with dantrolene in a concentration sufficient to inhibit the angiotensin II-induced mobilization of intracellular calcium. Also, if A23187 is added to cells simultaneously with 1-oleoyl-2-acetylglycerol (OAG), the aldosterone secretory response is similar to that seen after angiotensin II. However, if A23187 is added first and the transient aldosterone secretory response allowed to decay, and OAG then added, the sustained aldosterone secretory response is only 45-50% of maximal. Addition of the calcium channel agonist, BAY K 8644, with OAG leads to an aldosterone secretory response which is only 50% of maximal, but if upon addition of OAG and BAY K 8644 the cells are also exposed for 5 min to media containing 8 mM K+, then the sustained secretory response is maximal. These data imply that the initial transient rise in the [Ca2+] of the cell cytosol plays a role in determining the extent to which C-kinase is shifted from its calcium-insensitive to its calcium-sensitive form. The second group of experiments examined the relationship between the sustained angiotensin II-induced increase in plasma membrane calcium influx and the sustained aldosterone secretory response. The results show that in the presence of 1 microM nitrendipine or 2 mM extracellular K+, angiotensin II causes no increase in calcium influx and only a transient rather than a sustained increase in the rate of aldosterone secretion indicating that the sustained phase of the response is dependent upon a continued high rate of Ca2+ influx which regulates the rate of turnover of the activated C-kinase.
当血管紧张素II刺激醛固酮分泌时，它会导致细胞内钙池快速但短暂地释放钙，并使肾上腺球状带细胞中的钙内流持续增加。进行本研究是为了确定血管紧张素II诱导的细胞钙代谢的两种变化在调节细胞反应持续阶段的事件中各自的作用，该阶段被认为是由钙信使系统的C激酶分支介导的。在用足以抑制血管紧张素II诱导的细胞内钙释放的浓度的丹曲林预处理的细胞中，对血管紧张素II的持续反应仅为最大值的50%。此外，如果将A23187与1-油酰基-2-乙酰甘油（OAG）同时添加到细胞中，醛固酮分泌反应与血管紧张素II作用后的反应相似。然而，如果先添加A23187并使短暂的醛固酮分泌反应衰减，然后再添加OAG，则持续的醛固酮分泌反应仅为最大值的45 - 50%。将钙通道激动剂BAY K 8644与OAG一起添加会导致醛固酮分泌反应仅为最大值的50%，但如果在添加OAG和BAY K 8644后，细胞也暴露于含有8 mM K+的培养基中5分钟，则持续分泌反应为最大值。这些数据表明，细胞胞质溶胶中[Ca2+]的初始短暂升高在确定C激酶从其钙不敏感形式转变为钙敏感形式的程度中起作用。第二组实验研究了血管紧张素II诱导的质膜钙内流持续增加与持续的醛固酮分泌反应之间的关系。结果表明，在存在1 microM尼群地平或2 mM细胞外K+的情况下，血管紧张素II不会导致钙内流增加，并且仅导致醛固酮分泌速率短暂而非持续增加，这表明反应的持续阶段依赖于持续的高钙内流速率，该速率调节活化的C激酶的周转速率。
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