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-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 GDPbetaS, 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.
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, CCS-bloco J, 21941-590 Rio de Janeiro, RJ, Brazil.
Lucienne S
LS
Lara
Diogo
D
Vives
Juliana S
JS
Correa
Flavia P
FP
Cardozo
Maria Fernanda
MF
Marques-Fernades
Anibal G
AG
Lopes
Celso
C
Caruso-Neves
D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine
D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D012964:Sodium; D017868:Cyclic AMP-Dependent Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase