The angiotensin receptor type 1-Gq protein-phosphatidyl inositol phospholipase Cbeta-protein kinase C pathway is involved in activation of proximal tubule Na+-ATPase activity by angiotensin(1-7) in pig kidneys

• Published in: Experimental physiology 2008-05, Vol.93 (5), p.639-647
• Main Authors: Lara, Lucienne S, Correa, Juliana S, Lavelle, Anouchka B, Lopes, Anibal G, Caruso-Neves, Celso
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - metabolism; Angiotensin I - pharmacology; Animals; Blood Pressure - physiology; Cation Transport Proteins - metabolism; Diglycerides - metabolism; Enzyme Activation - drug effects; Extracellular Space - physiology; GTP-Binding Protein alpha Subunits, Gq-G11 - physiology; Hydroxylamines - pharmacology; Kidney Tubules, Proximal - enzymology; Peptide Fragments - pharmacology; Phosphatidylinositols - physiology; Phospholipase C beta - physiology; Phosphorylation; Protein Kinase C - physiology; Receptor, Angiotensin, Type 1 - physiology; Signal Transduction - physiology; Sodium - urine; Swine
• ISSN: 0958-0670
• DOI: 10.1113/expphysiol.2007.040584

In a previous study, we observed that angiotensin(1-7) (Ang(1-7)) stimulates proximal tubule Na+-ATPase activity through the angiotensin receptor type 1 (AT1R). Here we aimed to study the signalling pathways involved. Our results show that the stimulatory effect of Ang(1-7) on Na+-ATPase activity through AT1R involves a Gq protein-phosphatidyl inositol-phospholipase Cbeta (PI-PLCbeta) pathway because: (1) the effect was reversed by GDPbetaS, a non-hydrolysable GDP analogue, and by a monoclonal Gq protein antibody; (2) the effect was similar and not additive to that of GTPgammaS, a non-hydrolysable GTP analogue; (3) Ang(1-7) induced a rapid decrease (30 s) in phosphatidylinositol 4,5-bisphosphate levels, a PI-PLCbeta substrate; and (4) U73122, a specific inhibitor of PI-PLCbeta, abolished Ang(1-7)-induced stimulation of Na+-ATPase activity. Angiotensin(1-7) increased the protein kinase C (PKC) activity similarly to phorbol-12-myristate-13-acetate (PMA), an activator of PKC. This effect was reversed by losartan, a specific antagonist of AT1R. The stimulatory effects of Ang(1-7) and PMA on Na+-ATPase activity are similar, non-additive and reversed by calphostin C, a specific inhibitor of PKC. A catalytic subunit of PKC (PKC-M) increased the Na+-ATPase activity. These data show that Ang(1-7) stimulates Na+-ATPase activity through the AT1R-Gq protein-PI-PLCbeta-PKC pathway. This effect is similar to that described for angiotensin II, showing for the first time that these compounds could have similar effects in the renal system.