Vasopressin‐dependent upregulation of aquaporin‐2 gene expression in aged rats with glucocorticoid deficiency

Acta Physiologica (Impact Factor: 4.38). 11/2008; 196(2):239 - 247. DOI: 10.1111/j.1748-1716.2008.01938.x


Aim: The study was undertaken to determine whether ageing affects kidney expression of the aquaporin-2 (AQP2) water channel in glucocorticoid-deficient rats.
Methods: After adrenalectomy, 6- and 52-week-old Sprague–Dawley rats received aldosterone via osmotic minipumps (glucocorticoid-deficient rats). Aldosterone and dexamethasone were administered to control rats of the same age.
Results: An acute water load test verified impairment of water excretion in both young and aged rats with glucocorticoid deficiency, with a more serious impairment in the older rats. Despite the presence of hypoosmolality, non-suppressible release of arginine vasopressin (AVP) was particularly evident in the aged rats with glucocorticoid deficiency in comparison with the young rats. The expression levels of AQP2 mRNA and protein were lower in the aged rats, with a particularly large reduction in AQP2 protein expression. AQP2 expression levels were significantly augmented in the glucocorticoid-deficient rats compared with the controls under both basal and water-loaded conditions. Acute water loading did not suppress expression of AQP2 mRNA and protein, and the percentage increases in AQP2 mRNA and protein expression vs. the respective controls were more pronounced in the 52-week-old glucocorticoid-deficient rats compared with the 6-week-old rats.
Conclusion: The findings indicate that upregulation of AQP2 expression is maintained dependent upon non-suppressible release of AVP in rats with glucocorticoid deficiency, and that AQP2 plays a crucial role in persistent impairment of water excretion in aged rats with glucocorticoid deficiency.

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    • "Dysfunction of AQP2 is linked to many water related diseases, such as central and nephrogenic diabetes insipidus, chronic heart failure, and nephrotic syndrome (Jaffuel et al., 2013). Arginine vasopressin (AVP, also named antidiuretic hormone, ADH) is the major hormone that regulates AQP2 activity in vivo (Saito et al., 2009; Fenton et al., 2013). Vasopressin binds to the V 2 vasopressin receptor on the basolateral side of collecting duct principal cells and activates a cAMP-dependent signal transduction pathway. "
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    ABSTRACT: Aquaporin-2 (AQP2) is the vasopressin-regulated water channel that controls renal water reabsorption and plays an important role in the maintenance of body water homeostasis. Excessive glucocorticoid as often seen in Cushing's syndrome causes water retention. However, whether and how glucocorticoid regulates AQP2 remains unclear. In this study, we examined the direct effect of dexamethasone on AQP2 protein expression and activity. Dexamethasone increased AQP2 protein abundance in rat inner medullary collecting duct (IMCD) suspensions. This was confirmed in HEK293 cells transfected with AQP2 cDNA. Cell surface protein biotinylation showed an increase of dexamethasone-induced cell membrane AQP2 expression and this effect was blocked by glucocorticoid receptor antagonist RU486. Functionally, dexamethasone treatment of oocytes injected with an AQP2 cRNA increased water transport activity as judged by cell rupture time in a hypo-osmotic solution (66 ± 13 s in dexamethasone vs. 101 ± 11 s in control, n = 15). We further found that dexamethasone treatment reduced AQP2 protein degradation, which could result in an increase of AQP2 protein. Interestingly, dexamethasone promoted cell membrane AQP2 moving to less buoyant lipid raft submicrodomains. Taken together, our data demonstrate that dexamethasone promotes AQP2 protein expression and increases water permeability mainly via inhibition of AQP2 protein degradation. The increase in AQP2 activity promotes water reabsorption, which may contribute to glucocorticoid-induced water retention and hypertension.
    Frontiers in Physiology 11/2015; 6. DOI:10.3389/fphys.2015.00310 · 3.53 Impact Factor
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    Postepy Biologii Komorki 01/2010; 37(4):837-848. · 0.20 Impact Factor