Received October 25, 2007
Revised December 3, 2007
Accepted after revision January 29, 2008

¹ Universidade Federal do Rio de Janeiro

^* To whom correspondence should be addressed. E-mail: caruso{at}biof.ufrj.br.

	Abstract

In a previous study, we observed that angiotensin-(1-7) (Ang-(1-7)) stimulates proximal tubule Na+-ATPase activity through 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/PI-PLC pathway because: (1) the effect was reversed by GDPS, a non-hydrolysable GDP analogue, and by the monoclonal Gq 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 PIP2 levels, a PI-PLC substrate; (4) U73122, a specific inhibitor of PI-PLC abolished Ang-(1-)-stimulation of Na+-ATPase activity. Ang-(1-7) increased the PKC activity similarly to 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-PLC/PKC pathway. This effect is similar to that described for Ang II, showing for the first time that these compounds could have similar effects in the renal system.

Key Words: Angiotensin, ATPase, Proximal tubule

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