血管紧张素II刺激的皮质醇分泌由磷脂酶D介导。

Angiotensin II-stimulated cortisol secretion is mediated by phospholipase D.

作者信息

Rábano Miriam, Peña Ana, Brizuela Leyre, Macarulla José María, Gómez-Muñoz Antonio, Trueba Miguel

机构信息

Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain.

出版信息

Mol Cell Endocrinol. 2004 Jul 30;222(1-2):9-20. doi: 10.1016/j.mce.2004.05.006.

DOI:10.1016/j.mce.2004.05.006

PMID:15249121

Abstract

Angiotensin II (Ang-II) regulates a variety of cellular functions including cortisol secretion. In the present report, we demonstrate that Ang-II activates phospholipase D (PLD) in zona fasciculata (ZF) cells of bovine adrenal glands, and that this effect is associated to the stimulation of cortisol secretion by this hormone. PLD activation was dependent upon extracellular Ca2+, and was blocked by inhibition of protein kinase C (PKC). Using the reverse transcription-polymerase chain reaction technique, we demonstrated that ZF cells express both PLD-1 and PLD-2 isozymes. Primary alcohols, which attenuate the formation of phosphatidate (the product of PLD), and cell-permeable ceramides, which inhibit PLD potently, blocked Ang-II-stimulated cortisol secretion. Furthermore, propranolol or chlorpromazine, which are potent inhibitors of phosphatidate phosphohydrolase (PAP) (the enzyme that produces diacylglycerol from phosphatidate), also blocked cortisol secretion. These data suggest that the PLD/PAP pathway plays an important role in the regulation of cortisol secretion by Ang-II in ZF cells.

摘要

血管紧张素 II（Ang-II）调节多种细胞功能，包括皮质醇分泌。在本报告中，我们证明 Ang-II 可激活牛肾上腺束状带（ZF）细胞中的磷脂酶 D（PLD），且这种作用与该激素对皮质醇分泌的刺激有关。PLD 的激活依赖于细胞外 Ca2+，并可被蛋白激酶 C（PKC）的抑制所阻断。利用逆转录-聚合酶链反应技术，我们证明 ZF 细胞同时表达 PLD-1 和 PLD-2 同工酶。可减弱磷脂酸（PLD 的产物）形成的伯醇以及能有效抑制 PLD 的细胞可渗透神经酰胺，均可阻断 Ang-II 刺激的皮质醇分泌。此外，作为磷脂酸磷酸水解酶（PAP，一种由磷脂酸产生二酰甘油的酶）的强效抑制剂的普萘洛尔或氯丙嗪，也可阻断皮质醇分泌。这些数据表明，PLD/PAP 途径在 Ang-II 对 ZF 细胞皮质醇分泌的调节中起重要作用。