PKA-mediated effect of MAS receptor in counteracting angiotensin II-stimulated renal Na super(+)-ATPase

• Published in: Archives of biochemistry and biophysics 2010-04, Vol.496 (2), p.117-122
• Main Authors: Lara, Lucienne S, Vives, Diogo, Correa, Juliana S, Cardozo, Flavia P, Marques-Fernades, Maria Fernanda, Lopes, Anibal G, Caruso-Neves, Celso
• Format: Article
• Language: English
• ISSN: 0003-9861
• DOI: 10.1016/j.abb.2010.02.005

We showed previously that angiotensin-(1-7) [Ang-(1-7)] reversed stimulation of proximal tubule Na super(+)-ATPase promoted by angiotensin II (Ang II) through a d-ala super(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 super(+)-ATPase by a Gs/PKA pathway because: (1) the Ang-(1-7) effect is reversed by GDPbS, 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, 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 super(+)-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 super(+)-ATPase. Our results provide new understanding about the signaling mechanisms coupled to MAS receptor-mediated renal Ang-(1-7) effects.