title: Angiotensin II stimulates H⁺-ATPase activity in intercalated cells from isolated mouse connecting tubules and cortical collecting ducts.
abstract: Intercalated cells in the collecting duct system express V-type H(+)-ATPases which participate in acid extrusion, bicarbonate secretion, and chloride absorption depending on the specific subtype. The activity of H(+)-ATPases is regulated by acid-base status and several hormones, including angiotensin II and aldosterone. Angiotensin II stimulates chloride absorption mediated by pendrin in type B intercalated cells and this process is energized by the activity of H(+)-ATPases. Moreover, angiotensin II stimulates bicarbonate secretion by the connecting tubule (CNT) and early cortical collecting duct (CCD). In the present study we examined the effect of angiotensin II (10 nM) on H(+)-ATPase activity and localization in isolated mouse connecting tubules and cortical collecting ducts. Angiotensin II stimulated Na(+)-independent intracellular pH recovery about 2-3 fold, and this was abolished by the specific H(+)-ATPase inhibitor concanamycin. The effect of angiotensin II was mediated through type 1 angiotensin II receptors (AT(1)-receptors) because it could be blocked by saralasin. Stimulation of H(+)-ATPase activity required an intact microtubular network--it was completely inhibited by colchicine. Immunocytochemistry of isolated CNT/CCDs incubated in vitro with angiotensin II suggests enhanced membrane associated staining of H(+)-ATPases in pendrin expressing intercalated cells. In summary, angiotensin II stimulates H(+)-ATPases in CNT/CCD intercalated cells, and may contribute to the regulation of chloride absorption and bicarbonate secretion in this nephron segment.
authors: Department of Cellular and Molecular Physiology, School of Medicine, Yale University, New Haven, CT, USA. Wagnerca@access.uzh.ch
authors: Carsten A
authors: CA
authors: Wagner
authors: Nilufar
authors: N
authors: Mohebbi
authors: Ulrike
authors: U
authors: Uhlig
authors: Gerhard H
authors: GH
authors: Giebisch
authors: Sylvie
authors: S
authors: Breton
authors: Dennis
authors: D
authors: Brown
authors: John P
authors: JP
authors: Geibel
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000201:enzymology* / Q000473:pathology; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011945:Receptors, Angiotensin / Q000737:chemistry / Q000378:metabolism; D012504:Saralasin / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D000076988:Sulfate Transporters; D025262:Vacuolar Proton-Translocating ATPases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D027321:Anion Transport Proteins; D001639:Bicarbonates; D002712:Chlorides; D018942:Macrolides; D011945:Receptors, Angiotensin; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters; D000804:Angiotensin II; C036978:concanamycin A; D012964:Sodium; D025262:Vacuolar Proton-Translocating ATPases; D012504:Saralasin; D003078:Colchicine