Vasopressin V1a Receptor of Renal Collecting Duct Intercalated Cells Promotes Urinary Proton Secretion

• DOI: 10.1096/fasebj.2019.33.1_supplement.862.20
• Publication Date: 2021-06-22T00:29:22Z
• Authors: Torsten Giesecke; Taka‐Aki Koshimizu; Katsumasa Kawahara; Niclas Gimber; Jan Schmoranzer; Nina Himmerkus; Julian Isermann; Markus Bleich; Niklas Assay; Jens Leipziger; Michael Fähling; Alina Smorodchenko; Sebastian Bachmann; Kerim Mutig
• Keywords: Intercalated Cell; Renal medulla

Antagonists of the V1a vasopressin receptor (V1aR) are emerging as a therapeutic strategy for retardation chronic kidney disorders. Physiologically, V1aR signaling has been linked with acid‐base homeostasis, although underlying mechanisms remain debatable. In this study, we tested hypothesis that activation in type A intercalated cells (A‐ICs) induces urinary H+ secretion. We generated an anti‐V1aR antibody and verified its specificity using V1aR‐knockout tissues. Localization studies mice, rat human tissue, were preformed immunofluorescence confocal microscopy or 3D‐structured illumination (3D‐SIM). For functional vivo , V1aR‐specific agonist, AO‐4‐67, was administered AVP‐deficient Brattleboro rats C57/BI6J mice (0.2, 2, 10μg/kg b.w.; 1 to 4h). Urine collected metabolic cages via ureteral catheter plasma samples taken. Isolated, microperfused mouse collecting ducts analyzed V1aR‐dependent luminal pH changes cultured inner medullary duct proton‐secreting vH + ‐ATPase regulation. mouse, kidneys produced basolateral signal A‐ICs perinuclear subapical B connecting tubules throughout these species. addition, detected macula densa but not kidneys. Administration A0‐4‐67, significantly decreased vasopressin‐deficient (10 μ g/kg body weight 4 hours i.p.; 7.38 6.71 after hour, P<0.01) (2 hour 7.18 6.78 20 minutes, P<0.05). Basolateral treatment isolated perfused agonist increased intracellular Ca2+ levels (pH −5% 3 P<0.05) suggesting release stimulation proton secreting proteins. induced translocation vacuolar H+‐ATPase (apical intensity +93%, P<0.001). summary, our results show contributes acidification secretion by A‐ICs, which may have clinical implications pharmacological targeting V1aR. This abstract is from Experimental Biology 2019 Meeting. There no full text article associated published The FASEB Journal .