Giesecke, Torsten, Himmerkus, Nina, Leipziger, Jens, Bleich, Markus, Koshimizu, Taka-aki, Fähling, Michael, Smorodchenko, Alina, Shpak, Julia, Knappe, Carolin, Isermann, Julian, Ayasse, Niklas, Kawahara, Katsumasa, Schmoranzer, Jan, Gimber, Niclas, Paliege, Alexander, Bachmann, Sebastian and Mutig, Kerim (2019) Vasopressin Increases Urinary Acidification via V1a Receptors in Collecting Duct Intercalated Cells. Journal of the American Society of Nephrology, 30 (6). pp. 946-961. DOI 10.1681/ASN.2018080816.

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Abstract

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.

Document Type:	Article
Keywords:	acid-base homeostasis, antidiuretic Hormone, distal renal tubular Acidosis, intercalated cells, vasopressin V1a receptor, V-ATPase
Research affiliation:	Kiel University > Kiel Marine Science OceanRep > The Future Ocean - Cluster of Excellence Kiel University
Refereed:	Yes
Open Access Journal?:	No
Publisher:	American Society of Nephrology
Projects:	Future Ocean
Date Deposited:	01 Aug 2019 10:45
Last Modified:	02 Jan 2020 12:16
URI:	https://oceanrep.geomar.de/id/eprint/47309

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