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This Article Full Text Full Text (PDF) All Versions of this Article: 93/5/639    most recent expphysiol.2007.040584v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lara, L. S. Articles by Caruso-Neves, C. Search for Related Content PubMed PubMed Citation Articles by Lara, L. S. Articles by Caruso-Neves, C. Related Collections Themed Issue papers Renal

¹ Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas² Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

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 G_q protein–phosphatidyl inositol-phospholipase Cβ (PI-PLCβ) pathway because: (1) the effect was reversed by GDPβS, a non-hydrolysable GDP analogue, and by a monoclonal G_q protein antibody; (2) the effect was similar and not additive to that of GTPS, a non-hydrolysable GTP analogue; (3) Ang(1–7) induced a rapid decrease (30 s) in phosphatidylinositol 4,5-bisphosphate levels, a PI-PLCβ substrate; and (4) U73122 [GenBank] , a specific inhibitor of PI-PLCβ, 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–G_q protein–PI-PLCβ–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.

(Received 25 October 2007; accepted after revision 29 January 2008; first published online 1 February 2008)
Corresponding author C. C. Neves: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS-bloco G, 21941-902, Rio de Janeiro, RJ, Brazil. Email: caruso{at}biof.ufrj.br