Angiotensin II stimulates vacuolar H+ -ATPase activity in renal acid-secretory intercalated cells from the outer medullary collecting duct.
Final urinary acidification is mediated by the action of vacuolar H(+)-ATPases expressed in acid-secretory type A intercalated cells (A-IC) in the collecting duct. Angiotensin II (AngII) has profound effects on renal acid-base transport in the proximal tubule, distal tubule, and collecting duct. This study investigated the effects on vacuolar H(+)-ATPase activity in A-IC in freshly isolated mouse outer medullary collecting ducts. AngII (10 nM) stimulated concanamycin-sensitive vacuolar H(+)-ATPase activity in A-IC in freshly isolated mouse outer medullary collecting ducts via AT(1) receptors, which were also detected immunohistochemically in A-IC. AngII increased intracellular Ca(2+) levels transiently. Chelation of intracellular Ca(2+) with BAPTA and depletion of endoplasmic reticulum Ca(2+) stores prevented the stimulatory effect on H(+)-ATPase activity. The effect of AngII on H(+)-ATPase activity was abolished by inhibitors of small G proteins and phospholipase C, by blockers of Ca(2+)-dependent and -independent isoforms of protein kinase C and extracellular signal-regulated kinase 1/2. Disruption of the microtubular network and cleavage of cellubrevin attenuated the stimulation. Finally, AngII failed to stimulate residual vacuolar H(+)-ATPase activity in A-IC from mice that were deficient for the B1 subunit of the vacuolar H(+)-ATPase. Thus, AngII presents a potent stimulus for vacuolar H(+)-ATPase activity in outer medullary collecting duct IC and requires trafficking of stimulatory proteins or vacuolar H(+)-ATPases. The B1 subunit is indispensable for the stimulation by AngII, and its importance for stimulation of vacuolar H(+)-ATPase activity may contribute to the inappropriate urinary acidification that is seen in patients who have distal renal tubular acidosis and mutations in this subunit.
Rothenberger
Florina
F
Institute of Physiology and Centre for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, Zurich, Switzerland.
Velic
Ana
A
Stehberger
Paul A
PA
Kovacikova
Jana
J
Wagner
Carsten A
CA
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D007685:Kidney Tubules, Collecting / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*
D000804:Angiotensin II; D025262:Vacuolar Proton-Translocating ATPases