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

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-ala7-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: (1) the Ang-(1–7) effect is reversed by GDPβS, 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.