Regulation of the renal Na-HCO3 cotransporter: IV. Mechanisms of the stimulatory effect of angiotensin II.
Angiotensin II stimulates proximal tubule acidification by activating both the Na-H antiporter and the Na-HCO3 cotransporter. The mechanism whereby angiotensin II stimulates the Na-HCO3 cotransporter was investigated in renal cortical basolateral membrane vesicles of the rabbit by measuring 22Na uptake in the presence of HCO3 and gluconate. Na-HCO3 cotransporter activity (expressed in nanomoles per milligram of protein per 3 s) was taken as the difference in 22Na uptake in the presence of HCO3 and gluconate. Angiotensin II stimulated Na-HCO3 cotransporter activity significantly (control, 1.5 +/- 0.4; angiotensin II, 3.3 +/- 0.6; P < 0.05), and this stimulation was prevented by the angiotensin II receptor antagonist DuP 753. Angiotensin II has been shown to stimulate both pertussis toxin-sensitive Gi protein and pertussis toxin-insensitive Gq protein. In the presence of pertussis toxin, angiotensin II (10(-11) M) failed to stimulate the Na-HCO3 cotransporter, suggesting a role of Gi protein in mediating this effect. In the presence of a polyclonal antibody against Gi protein, angiotensin II failed to stimulate the Na-HCO3 cotransporter (control, 1.6 +/- 0.4; angiotensin II, 3.9 +/- 0.9; angiotensin II + Gi, 1.2 +/- 0.7). Angiotensin II stimulated inositol triphosphate release, and this effect could be blocked by the phospholipase C inhibitor U73122, suggesting a role of phospholipase C or A2 in this effect of angiotensin II. In the presence of the protein kinase C inhibitor calphostin C (50 nM), angiotensin II also failed to stimulate the Na-HCO3 cotransporter. These results demonstrate that angiotensin II stimulates the renal Na-HCO3 cotransporter by interacting with a specific angiotensin II receptor and that this stimulation is mediated by the activation of Gi and Gq proteins.
Ruiz
O S
OS
Section of Nephrology, University of Illinois at Chicago, USA.
Qiu
Y Y
YY
Wang
L J
LJ
Arruda
J A
JA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology; D010741:Phospholipases A / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011817:Rabbits; D027982:Sodium-Bicarbonate Symporters; D010738:Type C Phospholipases / Q000502:physiology
D001639:Bicarbonates; D002352:Carrier Proteins; D027982:Sodium-Bicarbonate Symporters; D000804:Angiotensin II; D011493:Protein Kinase C; D010741:Phospholipases A; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins