Abstract: SA-PO1033
Comparative Analysis of Vasopressin V1a Receptor Distribution in Rodent and Human Kidneys
Session Information
- Water/Urea/Vasopressin, Organic Solutes
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Fluid, Electrolytes, and Acid-Base
- 702 Water/Urea/Vasopressin, Organic Solutes
Authors
- Giesecke, Torsten, Charité Universitätsmedizin Berlin, Berlin, Germany
- Koshimizu, Taka-aki, Jichi Medical University, Shimostuke, Tochigi, Japan
- Kawahara, Katsumasa, Dept of Physiol, Kitasato Univ School of Med, Sagamihara, Japan
- Himmerkus, Nina, Christian Albrechts Universität Kiel, Kiel, Germany
- Isermann, Julian, Christian Albrechts Universität Kiel, Kiel, Germany
- Bleich, Markus, Christian Albrechts Universität Kiel, Kiel, Germany
- Smorodchenko, Alina, Charité Universitätsmedizin Berlin, Berlin, Germany
- Bachmann, Sebastian, Charité Universitätsmedizin Berlin, Berlin, Germany
- Mutig, Kerim, Charité Universitätsmedizin Berlin, Berlin, Germany
Background
Selective antagonists of V1a vasopressin receptor (V1aR) have been discussed as an emerging therapeutic strategy for retardation of chronic kidney disorders. Therefore, detailed knowledge of renal V1aR distribution is fundamental. This work provides comparative analysis of segmental and cellular localization of the receptor in mouse, rat, and human kidney supported by functional studies.
Methods
Immunofluorescence and high-resolution immunocytochemistry using own antibody to V1aR were performed for localization studies. Functional experiments with a V1aR agonist (AO-4-67) were conducted in vivo cultured cells and isolated, perfused renal tubules.
Results
Incubation of mouse kidney sections with the anti-V1aR antibody produced basolateral signal in macula densa cells and in type-A intercalated cells of connecting tubules and collecting ducts, whereas type-B intercalated cells showed punctate perinuclear and apical V1aR signal. In the rat and human kidneys, both types of intercalated cells exhibited chiefly diffused intracellular or apical V1aR signal patterns, whereas macula densa cells did not show any significant V1aR immunoreactivity. Administration of AO-4-67 to vasopressin-deficient Brattleboro rats for 4h induced luminal trafficking of V-ATPase in type-A intercalated cells suggesting increased proton secretion. Accordingly, treatment of isolated mouse collecting ducts with vasopressin or AO-4-67 decreased the luminal pH. Cultured mouse macula densa cells responded to the agonist with rise of intracellular calcium, which verified the V1aR presence in this cell type in mice.
Conclusion
In summary, these results suggest that activation of V1aR modulates function of intercalated cells across the studied species, whereas effects in macula densa cells may be restricted to the mouse species.