Abstract
Ensuring the proper amount of water inside the body is essential for survival. One of the key factors in the maintenance of body water balance is water reabsorption in the collecting ducts of the kidney, a process that is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and impermeable to ions or other small molecules. Impairments of AQP2 result in various water balance disorders, including nephrogenic diabetes insipidus (NDI), which is a disease characterized by a massive loss of water through the kidney and consequent severe dehydration. Dysregulation of AQP2 is also a cause of water retention with hyponatremia in heart failure, hepatic cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Antidiuretic hormone vasopressin is an upstream regulator of AQP2. Its binding to the vasopressin V2 receptor promotes AQP2 targeting to the apical membrane and thus enables water reabsorption. Tolvaptan, a vasopressin V2 receptor antagonist, is effective and widely used for water retention with hyponatremia. However, there are no studies showing improvement in hard outcomes or long-term prognosis. A possible reason is that vasopressin receptors have many downstream effects other than AQP2 function. It is expected that the development of drugs that directly target AQP2 may result in increased treatment specificity and effectiveness for water balance disorders. This review summarizes recent progress in studies of AQP2 and drug development challenges for water balance disorders.
Highlights
Maintaining water balance is essential for cell function and organism survival
In addition to AQP2 trafficking to the apical membrane, this study indicates that the water transport activity of individual AQP2 is involved in the regulation of water reabsorption from the urine in kidney collecting ducts
This region is essential for AQP2 translocation, with mutations impairing its translocation to the apical membrane, the water channel function of these mutants is preserved [73,74,75,76]
Summary
The key event for its maintenance is water reabsorption in the collecting ducts, the terminal structure in the nephron [1] This process is strictly regulated by the vasopressin-sensitive water channel aquaporin-2 (AQP2) [2,3,4,5,6,7,8]. Circulating vasopressin binds to the vasopressin V2 receptor on the basolateral membrane of the principal cells of the renal collecting duct and activates signal transductions promoting AQP2 translocation from the intracellular vesicles to the apical membrane, which enables water reabsorption from the urinary tubule. Vasopressin can induce water reabsorption for 24 h or more by enhancing AQP2 transcription and its protein abundance in the collecting duct cells [16,17]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
