Bollag W B, Barrett P Q, Isales C M, Rasmussen H
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Endocrinology. 1991 Jan;128(1):231-41. doi: 10.1210/endo-128-1-231.
Angiotensin-II (Ang II) not only increases aldosterone secretion from bovine adrenal glomerulosa (AG) cells, but also primes these cells to respond to a subsequent challenge with the calcium channel agonist Bay K 8644. In cultured AG cells we investigated the hypothesis that this priming effect was the result of a persistent elevation in diacylglycerol (DAG) content. Ang II elicited an increase in DAG content, which was maintained for up to 75 min after the removal of Ang II, an effect which could underlie the ability of Ang II to prime the cells to respond to Bay K 8644. We then investigated the possibility that the DAG found in bovine AG cells consists of multiple species and the potential relationship of the species to the persistent elevation. We found that [3H]arachidonate and [14C]myristate were differentially incorporated into phospholipids, with approximately 80-85% of the latter radiolabel contained in phosphatidylcholine. Ang II elicited increases in the levels of both arachidonate- and myristate-containing DAG. The subsequent addition of an Ang II antagonist resulted in a rapid decrease in [3H]arachidonate-labeled DAG levels, but a much slower decline in myristate-containing DAG. These results suggest that the species of DAG generated in response to hormonal stimulation may be important in determining the speed with which this signal is terminated. Ang II also stimulated the release of water-soluble [3H]choline metabolites, in particular choline and phosphorylcholine, from prelabeled cells. These results indicate that 1) various DAG species exhibit different turnover rates; and 2) perhaps as a result of this disparity, the increase in DAG induced by an agonist may persist for a considerable period of time after the removal of the agonist or the inhibition of its action.
血管紧张素 II（Ang II）不仅能增加牛肾上腺球状带（AG）细胞中醛固酮的分泌，还能使这些细胞对随后钙通道激动剂 Bay K 8644 的刺激产生更强反应。在培养的 AG 细胞中，我们研究了这样一种假说，即这种致敏作用是二酰甘油（DAG）含量持续升高的结果。Ang II 可使 DAG 含量增加，在去除 Ang II 后，这种增加可持续长达 75 分钟，这一效应可能是 Ang II 使细胞对 Bay K 8644 产生致敏反应的基础。然后我们研究了牛 AG 细胞中发现的 DAG 可能由多种类型组成的可能性，以及这些类型与持续升高之间的潜在关系。我们发现，[3H]花生四烯酸和[14C]肉豆蔻酸被不同程度地掺入磷脂中，后者放射性标记约 80 - 85%存在于磷脂酰胆碱中。Ang II 可使含花生四烯酸和含肉豆蔻酸的 DAG 水平均升高。随后加入 Ang II 拮抗剂会导致[3H]花生四烯酸标记的 DAG 水平迅速下降，但含肉豆蔻酸的 DAG 下降速度要慢得多。这些结果表明，激素刺激产生的 DAG 类型可能对决定该信号终止的速度很重要。Ang II 还刺激了预标记细胞中水溶性[3H]胆碱代谢产物的释放，特别是胆碱和磷酸胆碱。这些结果表明：1）各种 DAG 类型表现出不同的周转率；2）也许由于这种差异，激动剂诱导的 DAG 增加在去除激动剂或抑制其作用后可能会持续相当长一段时间。
