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Author Notes:


J.D.K.: provided data, data analysis, and manuscript preparation and editing; J.M.S.: designed protocols, data analysis, and manuscript editing; Y.W.: carried out experiments, data collection and analysis, and wrote and finalized the manuscript. All authors have read and agreed to the published version of the manuscript.

The authors declare no conflict of interest.


Research Funding:

This work was supported by the American Society of Nephrology Carl W. Gottschalk Research Scholar Grant and the American Heart Association Career Development Grant #18CDA34060053 to Y. Wang.


  • adrenomedullin
  • aldosterone
  • calcineurin
  • phosphatase
  • protein phosphatase 2A
  • Rats
  • Animals
  • Rats, Sprague-Dawley
  • Membrane Transport Proteins
  • Phosphoric Monoester Hydrolases
  • Tacrolimus
  • Water
  • Adrenomedullin
  • Aquaporin 2
  • Calcineurin
  • Urea
  • Aldosterone
  • Vasopressins
  • Permeability
  • Kidney Tubules, Collecting

Phosphatases Decrease Water and Urea Permeability in Rat Inner Medullary Collecting Ducts


Journal Title:

International journal of molecular sciences


Volume 24, Number 7


Type of Work:

Article | Final Publisher PDF


We previously showed that the phosphatases PP1/PP2A and PP2B dephosphorylate the water channel, AQP2, suggesting their role in water reabsorption. In this study, we investigated whether protein phosphatase 2A (PP2A) and protein phosphatase 2B (PP2B or calcineurin), which are present in the inner medullary collecting duct (IMCD), are regulators of urea and water permeability. Inhibition of calcineurin by tacrolimus increased both basal and vasopressin-stimulated osmotic water permeability in perfused rat IMCDs. However, tacrolimus did not affect osmotic water permeability in the presence of aldosterone. Inhibition of PP2A by calyculin increased both basal and vasopressin-stimulated osmotic water permeability, and aldosterone reversed the increase by calyculin. Previous studies showed that adrenomedullin (ADM) activates PP2A and decreases osmotic water permeability. Inhibition of PP2A by calyculin prevented the ADM-induced decrease in water reabsorption. ADM reduced the phosphorylation of AQP2 at serine 269 (pSer269 AQP2). Urea is linked to water reabsorption by building up hyperosmolality in the inner medullary interstitium. Calyculin increased urea permeability and phosphorylated UT-A1. Our results indicate that phosphatases regulate water reabsorption. Aldosterone and adrenomedullin decrease urea or osmotic water permeability by acting through calcineurin and PP2A, respectively. PP2A may regulate water reabsorption by dephosphorylating pSer269, AQP2, and UT-A1.

Copyright information:

© 2023 by the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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