PKA-mediated effect of MAS receptor in counteracting angiotensin II-stimulated renal Na+-ATPase
PKA-mediated effect of MAS receptor in counteracting angiotensin II-stimulated renal Na+-ATPase
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DOI：
10.1016/j.abb.2010.02.005
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发表时间：
2010-04-15
影响因子：
3.9
通讯作者：
Caruso-Neves, Celso
中科院分区：
文献类型：
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作者：
Lara, Lucienne S.;Vives, Diogo;Caruso-Neves, Celso
我们以前发现血管紧张素-(1-7)[Ang-(1-7)[通过D-Ala(7)-Ang-(1-7)(A779)敏感受体逆转血管紧张素II(Ang II)促进的近端小管Na+-ATPase的刺激。在这里，我们研究了与该受体偶联的信号通路。根据我们的数据，Ang-(1-7)通过Gs/PKA通路产生MAS介导的对Ang II刺激的Na+-ATPase的逆转作用，这是因为：(1)Ang-(1-7)的作用可被G蛋白三聚体和Gs多克隆抗体的抑制剂S逆转。(2)在Ang II存在的情况下，Ang-(1-7)使PKA活性增加10倍；(3)PKA的多肽抑制剂阻断Ang-(1-7)对Ang II刺激的Na+-ATPase的作用；(4)Ang-(1-7)逆转Ang II刺激的PKC活性；(5)cAMP模拟Ang(1-7)对Ang II刺激的Na+-ATPase的作用。我们的结果提供了对MAS受体介导的肾脏Ang-(1-7)作用的信号机制的新理解。(C)2010 Elsevier Inc.保留所有权利。
We showed previously that angiotensin-(1-7) [Ang-(1-7)[ reversed stimulation of proximal tubule Na+-ATPase promoted by angiotensin II (Ang II) through a D-ala(7)-Ang-(1-7) (A779)-sensitive receptor. Here we investigated the signaling pathway coupled to this receptor. According to our data, Ang-( 1-7) produces a MAS-mediated reversal of Ang II-stimulated Na+-ATPase by a Gs/PKA pathway because: (I) the Ang-(1-7) effect is reversed by GDP beta S, an inhibitor of trimeric G protein and Gs polyclonal antibody. Cholera toxin, an activator of Gs protein, mimicked it; (2) in the presence of Ang II, Ang-( 1-7) increased the PKA activity 10-fold; (3) the peptide inhibitor of PKA blocked the Ang-(1-7) effect on Ang II-stimulated Na+-ATPase; (4) Ang-( 1-7) reverses the Ang II-stimulated PKC activity; (5) cAMP mimicked the Ang(1-7) effect on the Ang II-stimulated Na+-ATPase. Our results provide new understanding about the signaling mechanisms coupled to MAS receptor-mediated renal Ang-(1-7) effects. (C) 2010 Elsevier Inc. All rights reserved.