Pinet F, Mizrahi J, Laboulandine I, Menard J, Corvol P
J Clin Invest. 1987 Sep;80(3):724-31. doi: 10.1172/JCI113127.
The regulation of renin secretion was studied in continuous culture of human juxtaglomerular cells (JGC), which provided a permanent source of human renin production (Pinet, F., M. T. Corvol, F. Dench, J. Bourguignon, J. Feunteun, J. Ménard, and P. Corvol, 1985, Proc. Natl. Acad. Sci. USA, 82:8503-8507). 95% of the renin species secreted was prorenin, and therefore this study concerned primarily prorenin secretion. Renin production was stable, since the cells had been maintained in culture for more than two years. In culture, these human cells formed colonies of smooth musclelike cells, and electron microscopy showed the presence of cytoskeleton structures including myofibrils and attachment bodies. This human model was used to investigate the control of prorenin secretion in vitro at cellular level. Various pharmacological agents known to stimulate or inhibit renin secretion were tested in the cell cultures. The variations in prorenin secretion were measured in the supernatant. Forskolin, an independent receptor activator of adenylate cyclase, stimulated prorenin secretion in a dose-dependent manner and this stimulation was mediated by 3',5' cyclic-AMP (cAMP). Angiotensin II (AII) was found to inhibit prorenin secretion directly in a dose-dependent manner and atrial natriuretic factor (ANF), whose effects on human JGC were characterized for the first time, was also shown to exert such inhibition. When the effects of this inhibition by AII and ANF were tested on forskolin-mediated stimulation of prorenin secretion, the latter was inhibited and no change occurred in cAMP release. When JGC were treated with histamine, bradykinin, or one or two bradykinin analogues, the responses suggested that in these cells, H2-histamine receptors and kinin receptors are dependent on adenylate cyclase. One peptide, substance P, had an inhibitory effect on prorenin secretion but it was less important than AII and ANF. The present results demonstrate that the adenylate cyclase system of human JGC remains intact during culture and supports the hypothesis that cAMP is the second messenger and Cai2+, the final messenger involved in renin secretion. The cell system used here permits the evaluation of cellular responses and intracellular events in granulated cells in a human model.
在人球旁细胞（JGC）的连续培养中研究了肾素分泌的调节，该细胞系提供了一个永久性的人肾素产生来源（Pinet, F., M. T. Corvol, F. Dench, J. Bourguignon, J. Feunteun, J. Ménard, and P. Corvol, 1985, Proc. Natl. Acad. Sci. USA, 82:8503 - 8507）。分泌的肾素种类中95%是前肾素，因此本研究主要关注前肾素的分泌。肾素产生稳定，因为这些细胞已在培养中维持了两年多。在培养中，这些人细胞形成了平滑肌样细胞集落，电子显微镜显示存在包括肌原纤维和附着体在内的细胞骨架结构。这个人体模型用于在细胞水平体外研究前肾素分泌的调控。在细胞培养中测试了各种已知能刺激或抑制肾素分泌的药物制剂。在前体肾素分泌的变化测量上清液。福斯可林，一种腺苷酸环化酶的独立受体激活剂，以剂量依赖方式刺激前体肾素分泌，这种刺激由3',5' - 环磷酸腺苷（cAMP）介导。发现血管紧张素II（AII）以剂量依赖方式直接抑制前体肾素分泌，心房利钠因子（ANF），其对人JGC的作用首次得到表征，也显示出这种抑制作用。当测试AII和ANF的这种抑制作用对福斯可林介导的前体肾素分泌刺激的影响时，后者受到抑制，cAMP释放没有变化。当用组胺、缓激肽或一种或两种缓激肽类似物处理JGC时，反应表明在这些细胞中，H2组胺受体和激肽受体依赖于腺苷酸环化酶。一种肽，P物质，对前体肾素分泌有抑制作用，但不如AII和ANF重要。目前的结果表明，人JGC的腺苷酸环化酶系统在培养过程中保持完整，并支持cAMP是第二信使且Ca2 +是参与肾素分泌的最终信使这一假设。这里使用的细胞系统允许在人体模型中评估颗粒细胞中的细胞反应和细胞内事件。
