PKA-mediated effect of MAS receptor in counteracting angiotensin II-stimulated renal Na +-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
• Subjects: Angiotensin II; Angiotensin II - administration & dosage; Angiotensin-(1–7); Animals; Cells, Cultured; Cyclic AMP-Dependent Protein Kinases - metabolism; Kidney Tubules, Proximal - metabolism; MAS receptor signaling; Proto-Oncogene Proteins - metabolism; Receptors, G-Protein-Coupled - metabolism; Renal sodium excretion; Second sodium pump; Signal Transduction - physiology; Sodium - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism; Swine
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2010.02.005

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: (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.