Jens Georg Leipziger

Vasopressin Increases Urinary Acidification via V1a Receptors in Collecting Duct Intercalated Cells

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review


  • Torsten Giesecke, Charite - Universitatsmedizin Berlin, Berlin Institute of Health (BIH)
  • ,
  • Nina Himmerkus, Christian-Albrechts-Universität zu Kiel
  • ,
  • Jens Leipziger
  • Markus Bleich, Christian-Albrechts-Universität zu Kiel
  • ,
  • Taka Aki Koshimizu, Jichi Medical University
  • ,
  • Michael Fähling, School of Business and Economics
  • ,
  • Alina Smorodchenko, School of Business and Economics
  • ,
  • Julia Shpak, School of Business and Economics
  • ,
  • Carolin Knappe, School of Business and Economics
  • ,
  • Julian Isermann, Christian-Albrechts-Universität zu Kiel
  • ,
  • Niklas Ayasse
  • Katsumasa Kawahara, Kitasato University School of Medicine
  • ,
  • Jan Schmoranzer, School of Business and Economics
  • ,
  • Niclas Gimber, School of Business and Economics
  • ,
  • Alexander Paliege, University Hospital Carl Gustav Carus
  • ,
  • Sebastian Bachmann, School of Business and Economics
  • ,
  • Kerim Mutig, Charite - Universitatsmedizin Berlin, I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation (Sechenovskiy University)

BACKGROUND: Antagonists of the V1a vasopressin receptor (V1aR) are emerging as a strategy for slowing progression of CKD. Physiologically, V1aR signaling has been linked with acid-base homeostasis, but more detailed information is needed about renal V1aR distribution and function. METHODS: We used a new anti-V1aR antibody and high-resolution microscopy to investigate Va1R distribution in rodent and human kidneys. To investigate whether V1aR activation promotes urinary H+ secretion, we used a V1aR agonist or antagonist to evaluate V1aR function in vasopressin-deficient Brattleboro rats, bladder-catheterized mice, isolated collecting ducts, and cultured inner medullary collecting duct (IMCD) cells. RESULTS: Localization of V1aR in rodent and human kidneys produced a basolateral signal in type A intercalated cells (A-ICs) and a perinuclear to subapical signal in type B intercalated cells of connecting tubules and collecting ducts. Treating vasopressin-deficient Brattleboro rats with a V1aR agonist decreased urinary pH and tripled net acid excretion; we observed a similar response in C57BL/6J mice. In contrast, V1aR antagonist did not affect urinary pH in normal or acid-loaded mice. In ex vivo settings, basolateral treatment of isolated perfused medullary collecting ducts with the V1aR agonist or vasopressin increased intracellular calcium levels in ICs and decreased luminal pH, suggesting V1aR-dependent calcium release and stimulation of proton-secreting proteins. Basolateral treatment of IMCD cells with the V1aR agonist increased apical abundance of vacuolar H+-ATPase in A-ICs. CONCLUSIONS: Our results show that activation of V1aR contributes to urinary acidification via H+ secretion by A-ICs, which may have clinical implications for pharmacologic targeting of V1aR.

Original languageEnglish
JournalJournal of the American Society of Nephrology : JASN
Pages (from-to)946-961
Number of pages16
Publication statusPublished - 2019

    Research areas

  • acid-base homeostasis, antidiuretic hormone, distal renal tubular acidosis, intercalated cells, V-ATPase, vasopressin V1a receptor

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