Interactions among lithium, calcium, diacylglycerides, and phorbol esters in the regulation of adrenocorticotropin hormone release from AtT-20 cells.
Interactions among lithium, calcium, diacylglycerides, and phorbol esters in the regulation of adrenocorticotropin hormone release from AtT-20 cells.
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锂、钙、二酰基甘油酯和佛波酯之间的相互作用在调节 AtT-20 细胞促肾上腺皮质激素释放中的作用。
DOI：
10.1111/j.1471-4159.1987.tb00976.x
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发表时间：
1987
影响因子：
4.7
通讯作者：
Zatz,M
中科院分区：
文献类型：
--
作者：
Reisine,T;Zatz,M
在垂体前叶肿瘤细胞系 (AtT-20) 中检查了锂、钙和佛波酯在调节促肾上腺皮质激素 (ACTH) 释放中的相互作用。锂可以阻断将磷酸肌醇 (IP) 转化为肌醇的磷酸酶，从而增加这些细胞中 IP 的水平并刺激 ACTH 的释放。这种离子增强了钙（磷脂酶 C 的激活剂）的能力，提高这些细胞中 IP 的水平并刺激 ACTH 分泌。用钙预处理 AtT-20 细胞特异性地消除了对锂或钙的 ACTH 释放反应，这一结果表明这些促分泌剂可能通过一种共同的机制来诱导激素分泌。 AtT-20 细胞事先接触锂或钙也会减弱佛波酯（蛋白激酶 C 的激活剂）诱导的 ACTH 释放。为了检查锂、钙、磷脂酰肌醇 (PI) 周转和佛波酯诱发的 ACTH 分泌之间的联系，用 1-油酰基-2-乙酰酰基-ns-3-甘油 (OAG)（OAG 的类似物）处理 AtT-20 细胞。二酰基甘油，在 PI 代谢过程中由磷脂酶 C 形成，也激活蛋白激酶 C。OAG 本身不会改变 AtT-20 细胞中 ACTH 的释放或 IP 的水平。然而，用 OAG 预处理 AtT-20 细胞会选择性地阻断对锂、钙或佛波酯的 ACTH 释放反应。此外，这种预处理降低了锂提高IPs水平的能力。结果表明，锂的一种作用机制是选择性地增强钙的作用，可能是刺激磷脂酶 C 的活性。此外，二酰基甘油是磷脂酶 C 活性的产物，可反馈抑制对锂、钙和佛波酯的分泌反应。
Interactions among lithium, calcium, and phorbolesters in the regulation of adrenocorticotropin hormone (ACTH) release were examined in a tumor cell line (AtT‐ 20) of the anterior pituitary. Lithium, which blocks the phosphatase that converts inositol phosphates (IPs) to inositol, increases the levels of IPs in these cells and stimulates ACTH release. This ion potentiates the ability of calcium, an activator of phospholipase C, to raise levels of IPs in these cells and to stimulate ACTH secretion. Pretreatment of AtT‐20 cells with calcium specifically abolishes the ACTH release response to lithium or calcium, a result suggesting that these secretagogues may act through a common mechanism to induce hormone secretion. Prior exposure of AtT‐ 20 cells to either lithium or calcium also attenuates the ACTH release induced by phorbol ester, an activator of protein kinase C. To examine the link among lithium, calcium, phosphatidylinositol (PI) turnover, and phorbol esterevoked ACTH secretion, AtT‐20 cells were treated with 1‐oleoyl‐2‐acetoyl‐ns‐3‐glycerol (OAG), an analogue of the diacylgylcerols that are formed by phospholipase C during PI metabolism and that also activate protein kinase C. OAG itself does not alter ACTH release or the levels of IPs in AtT‐ 20 cells. Pretreatment of AtT‐20 cells with OAG, however, selectively blocks the ACTH release response to lithium, calcium, or phorbol ester. Furthermore, such pretreatment reduced the ability of lithium to increase levels of IPs. The results suggest that one mechanism of action of lithium is to potentiate selectively an action of calcium, possibly the stimulation of phospholipase C activity. In addition, diacylglycerol, a product of phospholipase C activity, acts to feedback inhibit the secretory response to lithium, calcium, and phorbol esters.