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

Abstract

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.

Acute and chronic angiotensin-(1–7) restores vasodilation and reduces oxidative stress in mesenteric arteries of salt-fed rats

“…Various studies in the literature have reported that the effects of ANG-(1-7) or AVE-0991 on different physiological systems are mediated either via its unique (mas) receptor alone (6,26,34,46) or involve AT 1 (8,18,23,32,34,48,53) and/or AT 2 (8,18,34,35,48,53) receptors acting in conjunction with the mas receptor. Therefore, an important question is whether the protective action of ANG-(1-7) and AVE-0991 to restore 6; B).…”

“…Because existing studies (6,8,11,23,26,32,34,35,46,48) have reached widely varying conclusions regarding the role of AT 1 and AT 2 receptors in mediating the response of diverse physiological systems to ANG-(1-7), we also determined whether any effect of ANG-(1-7) or AVE-0991 to restore vascular relaxation and endothelial function in SpragueDawley rats fed a HS diet is mediated solely via the mas receptor or whether AT 1 or AT 2 receptors contribute to the effects of ANG-(1-7). The ability of AT 2 receptor activation to restore endothelium-dependent vasodilation in salt-fed rats was also tested by acute and chronic administration of the AT 2 receptor agonist CGP-42112.…”

The ANG-(1–7)/ACE2/mas axis in the regulation of nephron function

“…Stimulatory effect of ANG II on the Na ϩ -ATPase activity in proximal tubules is reversed, in a dose-dependent manner, by ANG-(1-7) through the mas receptor (82). Later studies from the same laboratory indicate that ANG-(1-7) stimulates Na ϩ -ATPase activity through the AT1R-Gq protein-PI-PLC ␤-PKC pathway (83). Bradykinin counteracts the stimulatory effect of ANG-(1-7) on the proximal tubule Na ϩ -ATPase activity (23).…”

The second sodium pump: from the function to the gene

“…gills [173]; freshwater mussel ( Anodonta cygnea ) gills [77]; rainbow trout ( Oncorhynchus mykiss Walbaum ) gills [174]; rabbit cardiac sarcolemma [18]; malpighian tubules from Rhodnius prolixus [24, 25]; Trypanosoma cruzi epimastigotes [21, 145]; cultured MDCK I cells [39]; Entamoeba histolytica [38]; Leshmania amazonensis [36]; and pig kidney [79]. Recently, the Na + -ATPase activity has been reported in homogenates of several rat tissues [136].…”