Prostaglandin synthesis by rat glomerular mesangial cells in culture. Effects of angiotensin II and arginine vasopressin.
Prostaglandin synthesis by rat glomerular mesangial cells in culture. Effects of angiotensin II and arginine vasopressin.
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DOI：
10.1172/jci110931
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发表时间：
1983-06
期刊：
影响因子：
--
通讯作者：
L. Scharschmidt;M. Dunn
中科院分区：
文献类型：
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作者：
L. Scharschmidt;M. Dunn
精氨酸加压素（AVP）和血管紧张素II（ANG II）降低肾小球滤过率和超滤系数。血管扩张性前列腺素（PG）可以拮抗这些作用。 AVP 和 ANG II 也会引起系膜细胞收缩。因此，在培养的大鼠肾小球系膜细胞中研究了这些肽和两种加压素类似物可能对 PG 的刺激作用。还研究了改变钙利用率对 PG 产生的影响。将75-100g Sprague-Dawley大鼠的肾小球在补充营养培养基中培养28天，并在第一次传代时进行实验。通过电子显微镜证实系膜细胞形态。当与二价阳离子离子载体、A23187 或花生四烯酸 (C20:4) 一起孵育时，细胞产生的 PGE2 远大于 PGF2 α，大于 6-酮基-PGF1 α，大于血栓素 B2。 ANG II 和 AVP 在阈值浓度为 10 nM ANG II 和 100 pM AVP 时选择性刺激 PGE2。研究了抗利尿剂类似物 1-脱氨基-8-D-精氨酸加压素 (dDAVP) 和抗升压药类似物 [1-(β-巯基-β-环戊亚甲基丙酸)-4-缬氨酸，8-D-精氨酸]-加压素 (d[CH2]5VDAVP) 的作用。两种化合物均不会刺激 PGE2，并且与 d(CH2)5VDAVP 预孵育会被取消，并且 dDAVP 会减弱 AVP 增强的 PGE2 产生。在维拉帕米、硝苯地平或零钙培养基中孵育可阻断肽刺激的 PGE2 产生。增加细胞外钙或添加 A23187 会增加 PGE2 合成。系膜细胞中 ANG II 或 AVP 对 PGE2 的选择性刺激表明激素敏感的磷脂酶和偶联的环氧合酶只能合成 PGE2。由于加压素类似物均不刺激 PGE2，但均阻断 AVP 增强的 PGE2 产生，因此我们得出结论，这些细胞对 AVP 的升压活性有反应。这是一个依赖钙的过程。 ANG II 和 AVP 对 PGE2 的选择性刺激可能会调节它们对肾小球的收缩作用。
Arginine vasopressin (AVP) and angiotensin II (ANG II) reduce the glomerular filtration rate and ultrafiltration coefficient. Vasodilatory prostaglandins (PG) antagonize these effects. AVP and ANG II also cause mesangial cell contraction. Therefore, possible PG stimulation by these peptides and two vasopressin analogues was studied in cultured rat glomerular mesangial cells. The effect of altered calcium availability on PG production was also studied. Glomeruli from 75-100-g Sprague-Dawley rats were cultured in supplemented nutrient media for 28 d and experiments were performed on the first passage. Mesangial cell morphology was confirmed by electron microscopy. Cells produced PGE2 much greater than PGF2 alpha greater than 6-keto-PGF1 alpha greater than thromboxane B2 when incubated with the divalent cation ionophore, A23187, or arachidonic acid (C20:4). ANG II and AVP selectively stimulated PGE2 at threshold concentrations of 10 nM ANG II and 100 pM of AVP. The effects of the antidiuretic analogue 1-desamino-8-D-arginine vasopressin (dDAVP) and the antipressor analogue [1-(beta-mercapto-beta beta-cyclopentamethylene propionic acid)-4-valine, 8-D-arginine]-vasopressin (d[CH2]5VDAVP), were studied. Neither compound stimulated PGE2 and preincubation with d(CH2)5VDAVP abolished, and dDAVP blunted, AVP-enhanced PGE2 production. Incubation in verapamil, nifedipine, or zero calcium media blocked peptide-stimulated PGE2 production. Increasing extracellular calcium or adding A23187 increased PGE2 synthesis. Selective stimulation of PGE2 by ANG II or AVP in mesangial cells suggests a hormone-sensitive phospholipase and a coupled cyclooxygenase capable of synthesizing only PGE2. Since neither vasopressin analogue stimulated PGE2, but both blocked AVP-enhanced PGE2 production, we conclude that these cells respond to the pressor activity of AVP. This is a calcium-dependent process. Selective stimulation of PGE2 by ANG II and AVP may modulate their contractile effects on the glomerulus.