Angiotensin II stimulates vesicular H+-ATPase in rat proximal tubular cells.
Two mechanisms of H+ ion secretion in the proximal tubule that mediate bicarbonate reabsorption have been identified: the brush border Na/H exchanger and electrogenic H+ ion secretion. Angiotensin II (AII) has been shown to be a regulator of the luminal Na+/H+ exchanger and the basolateral Na+/HCO3- cotransporter. In the present study, we examined the effects of AII on H+-ATPase activity in isolated proximal tubule fragments. H+-ATPase activity was assessed by monitoring intracellular pH after Na+ removal from the bath. In addition, we investigated the effects on pH recovery of the proton pump inhibitor bafilomycin A1, removal of Cl-, and of colchicine. pH was continuously measured with the pH-sensitive fluorescent dye 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Recovery of cell pH was observed in the absence of external Na+ and was significantly accelerated by AII. The AII-stimulated pH recovery was completely abolished by bafilomycin A1, by removal of Cl-, by NPPB [5-nitro-2-(3-phenylpropylamino)-benzoate; a potent Cl- channel blocker], and by colchicine. We conclude from these studies that AII stimulates proton extrusion via H+-ATPase by a Cl--dependent process involving brush border insertion of vesicles. This process may contribute to up-regulation of HCO3- reabsorption along the proximal tubule when tubules are exposed to AII.
Wagner
C A
CA
Institute of Physiology I, University of Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany.
Giebisch
G
G
Lang
F
F
Geibel
J P
JP
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004789:Enzyme Activation; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism
D000804:Angiotensin II; D012964:Sodium; D006180:Proton-Translocating ATPases