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Kidney collecting duct cells make vasopressin in response to NaCl-induced hypertonicity
Juan Pablo Arroyo, … , Gautam Bhave, Raymond C. Harris
Juan Pablo Arroyo, … , Gautam Bhave, Raymond C. Harris
Published November 3, 2022
Citation Information: JCI Insight. 2022;7(24):e161765. https://doi.org/10.1172/jci.insight.161765.
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Research Article Nephrology

Kidney collecting duct cells make vasopressin in response to NaCl-induced hypertonicity

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Abstract

Vasopressin has traditionally been thought to be produced by the neurohypophyseal system and then released into the circulation where it regulates water homeostasis. The questions of whether vasopressin could be produced outside of the brain and if the kidney could be a source of vasopressin are raised by the syndrome of inappropriate antidiuretic hormone secretion (vasopressin). We found that mouse and human kidneys expressed vasopressin mRNA. Using an antibody that detects preprovasopressin, we found that immunoreactive preprovasopressin protein was found in mouse and human kidneys. Moreover, we found that murine collecting duct cells made biologically active vasopressin, which increased in response to NaCl-mediated hypertonicity, and that water restriction increased the abundance of kidney-derived vasopressin mRNA and protein expression in mouse kidneys. Thus, we provide evidence of biologically active production of kidney-derived vasopressin in kidney tubular epithelial cells.

Authors

Juan Pablo Arroyo, Andrew S. Terker, Yvonne Zuchowski, Jason A. Watts, Fabian Bock, Cameron Meyer, Wentian Luo, Meghan E. Kapp, Edward R. Gould, Adam X. Miranda, Joshua Carty, Ming Jiang, Roberto M. Vanacore, Elizabeth Hammock, Matthew H. Wilson, Roy Zent, Mingzhi Zhang, Gautam Bhave, Raymond C. Harris

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Figure 6

Inner medullary collecting duct cell medium contains a V2R-stimulating ligand.

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Inner medullary collecting duct cell medium contains a V2R-stimulating l...
(A) Bioassay experimental design to obtained conditioned medium from treated and untreated inner medullary collecting duct cells (IMCDs). (B and C) HEK-V2R-Luc cells stimulated with control and NaCl-treated IMCD medium had increased luciferase activity (lanes 4 and 5). The NaCl-mediated increase was blocked with the V2R antagonist OPC-31260 (lane 6). Data in C are presented as mean ± SD of total flux (photons per second). Data were analyzed with 1-way ANOVA with Tukey’s post hoc analysis, with a minimum of 4 independent replicates per group. #P < 0.0001 vs. control; ****P < 0.0001 vs. isotonic control; **P = 0.0018 vs. isotonic + NaCl.

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