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Angiotensin II stimulates vacuolar H+ -ATPase activity in renal acid-secretory intercalated cells from the outer medullary collecting duct


Rothenberger, F; Velic, A; Stehberger, P A; Kovacikova, J; Wagner, C A (2007). Angiotensin II stimulates vacuolar H+ -ATPase activity in renal acid-secretory intercalated cells from the outer medullary collecting duct. Journal of the American Society of Nephrology (JASN), 18(7):2085-2093.

Abstract

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:July 2007
Deposited On:20 Mar 2009 13:42
Last Modified:05 Apr 2016 13:03
Publisher:American Society of Nephrology
ISSN:1046-6673
Publisher DOI:10.1681/ASN.2006070753
PubMed ID:17561490
Permanent URL: http://doi.org/10.5167/uzh-14316

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