{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:40:00Z","timestamp":1791092400173,"version":"4.1.0"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,2,24]]},"abstract":"<jats:p>\n                    Renal collecting ducts play a critical role in acid\u2013base homeostasis by establishing steep transepithelial pH gradients necessary for the almost complete reabsorption of bicarbonate and the effective secretion of ammonium into the urine. The mechanisms of urine acidification in collecting ducts involve active, electrogenic hydrogen (H\n                    <jats:sup>+<\/jats:sup>\n                    ) secretion and, less importantly, potassium (K\n                    <jats:sup>+<\/jats:sup>\n                    )-H\n                    <jats:sup>+<\/jats:sup>\n                    exchange. Deranged renal acidification and the inability to lower urine pH are hallmarks of distal tubular acidosis and often result from inborn errors of metabolism involving vacuolar H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase subunits in the collecting ducts. Three factors regulate H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase activity in intercalated cells of collecting ducts: the acid\u2013base status, angiotensin II, and aldosterone. Most effects of aldosterone involve activation of the mineralocorticoid receptor and genomic changes in transcription and protein synthesis. Here we demonstrate a nongenomic pathway of vacuolar H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase activation in intercalated cells of isolated mouse outer medullary collecting ducts (OMCD).\n                    <jats:italic>In vitro<\/jats:italic>\n                    exposure of isolated outer medullary collecting ducts to aldosterone (10 nM) for times as short as 15 min increases vacuolar H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase activity \u22482- to 3-fold. Neither inhibition of mineralocorticoid receptors nor of transcription and protein synthesis prevented aldosterone-induced stimulation of H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase. Incubation with colchicine, however, abolished the stimulatory effect of aldosterone, suggesting a role of the microtubular network for H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase stimulation. Immunohistochemistry in kidneys from aldosterone-injected mice showed increased apical H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase staining in OMCD-intercalated cells. The stimulatory effect of aldosterone was associated with a transient rise in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and required intact PKC. Thus, rapid nongenomic modulation of vacuolar H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase activity in OMCD-intercalated cells by aldosterone may play an additional role in hormonal control of systemic acid\u2013base homeostasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0307321101","type":"journal-article","created":{"date-parts":[[2004,2,24]],"date-time":"2004-02-24T23:03:03Z","timestamp":1077663783000},"page":"2636-2641","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":106,"title":["Nongenomic stimulation of vacuolar H\n                    <sup>+<\/sup>\n                    -ATPases in intercalated renal tubule cells by aldosterone"],"prefix":"10.1073","volume":"101","author":[{"given":"Christian","family":"Winter","sequence":"first","affiliation":[{"name":"Institute of Physiology, University of Zurich, 8057 Zurich, Switzerland; and Departments of Cellular and Molecular Physiology and Surgery, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Schulz","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Zurich, 8057 Zurich, Switzerland; and Departments of Cellular and Molecular Physiology and Surgery, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Giebisch","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Zurich, 8057 Zurich, Switzerland; and Departments of Cellular and Molecular Physiology and Surgery, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Geibel","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Zurich, 8057 Zurich, Switzerland; and Departments of Cellular and Molecular Physiology and Surgery, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten A.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Physiology, University of Zurich, 8057 Zurich, Switzerland; and Departments of Cellular and Molecular Physiology and Surgery, Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,2,17]]},"reference":[{"key":"e_1_3_2_1_2","unstructured":"Brown D. & Breton S. 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