Angiotensin II increases vasopressin-stimulated facilitated urea permeability in rat terminal IMCDs
Angiotensin II increases vasopressin-stimulated facilitated urea permeability in rat terminal IMCDs
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DOI：
10.1152/ajprenal.2000.279.5.f835
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发表时间：
2000-11-01
影响因子：
4.2
通讯作者：
Sands, JM
中科院分区：
文献类型：
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作者：
Kato, A;Klein, JD;Sands, JM
血管紧张素II受体存在于大鼠的内髓集合管(IMCD)，尽管它们的生理作用尚不清楚。由于尿素是跨IMCD末端运输的主要溶质之一，我们测量了血管紧张素II对尿素通透性的影响。在灌流的大鼠IMCD末端，血管紧张素II对基础尿素通透性无影响，但显著增加血管加压素刺激的尿素通透性55%。血管紧张素II在没有和有血管加压素的情况下，也增加了体外暴露于这些激素的内髓组织中尿素转运体(UT)-A1中P-32的含量。因为血管紧张素II激活蛋白激酶C，所以我们测试了星形孢子素(SSP)的作用。在没有血管紧张素II的情况下，SSP对血管加压素刺激的IMCD末端的尿素通透性没有影响。然而，SSP完全可逆地阻断血管紧张素II介导的血管加压素刺激的尿素通透性增加。SSP和白屈菜红碱可减少血管紧张素II刺激的P-32掺入UT-A1。我们得出结论，血管紧张素II通过蛋白激酶C介导的信号通路增加血管加压素刺激的易化尿素通透性和P-32掺入97和117 kDa UT-A1蛋白。这些数据表明，血管紧张素II增强了加压素刺激的大鼠终末IMCD的易化尿素转运，并可能通过增强对加压素的最大反应而在尿浓缩机制中发挥生理作用。
Angiotensin II receptors are present along the rat inner medullary collecting duct (IMCD), although their physiological role is unknown. Because urea is one of the major solutes transported across the terminal IMCD, we measured angiotensin II's effect on urea permeability. In the perfused rat terminal IMCD, angiotensin II had no effect on basal urea permeability but significantly increased vasopressin-stimulated urea permeability by 55%. Angiotensin II, both without and with vasopressin, also increased the amount of P-32 incorporated into urea transporter (UT)-A1 in inner medullary tissue exposed to these hormones ex vivo. Because angiotensin II activates protein kinase C, we tested the effect of staurosporine (SSP). In the absence of angiotensin II, SSP had no effect on vasopressin-stimulated urea permeability in the perfused terminal IMCD. However, SSP completely and reversibly blocked the angiotensin II-mediated increase in vasopressin-stimulated urea permeability. SSP and chelerythrine reduced the angiotensin II-stimulated P-32 incorporation into UT-A1 in inner medullary tissue exposed ex vivo. We conclude that angiotensin II increases vasopressin-stimulated facilitated urea permeability and P-32 incorporation into the 97- and 117-kDa UT-A1 proteins via a protein kinase C-mediated signaling pathway. These data suggest that angiotensin II augments vasopressin-stimulated facilitated urea transport in the rat terminal IMCD and may play a physiological role in the urinary concentrating mechanism by augmenting the maximal response to vasopressin.