| Autor: |
Lara, Lucienne S., Correa, Juliana S., Lavelle, Anouchka B., Lopes, Anibal G., Caruso-Neves, Celso |
| Předmět: |
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| Zdroj: |
Experimental Physiology; May2008, Vol. 93 Issue 5, p639-647, 9p, 5 Graphs |
| Abstrakt: |
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 Cβ(PI-PLCβ) pathway because: (1) the effect was reversed by GDPβS, a non-hydrolysable GDP analogue, and by a monoclonal Gq protein antibody; (2) the effect was similar and not additive to that of GTPγS, 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, 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–Gq 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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