Vasopressin‐dependent upregulation of aquaporin‐2 gene expression in aged rats with glucocorticoid deficiency
(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.
Available from: PubMed Central
- "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.
Available from: Katarzyna Michałek
- "U ssaków przy braku stymulacji wazopresyn¹, akwaporyna zmagazynowana jest w pêcherzykach wewn¹trz komórek nab³onka kanalików nerkowych  . Liczne badania przeprowadzone u noworodków ludzkich oraz zwierz¹t laboratoryjnych wykaza³y zmniejszon¹ zdolnoae nerek do oszczêdzania wody     . Ograniczone mo¿liwoci kanalików nerkowych do zatrzymywania wody we wczesnym okresie pourodzeniowym s¹ wypadkow¹ dzia³ania wielu czynników. "
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ABSTRACT: Arginine vasopressin (AVP) related water resorption in the collecting duct acts through aquaporins 2 specific water channels. AQP2 are small integral tetrameric plasma membrane proteins. Each of four subunits is selectively permeable to water. In mammals lack of vasopressin stimulation causes AQP2 storage in intracellular vesicles of the principal cells of the renal distal tubule and collecting duct. AVP acts through specific V, receptors. Arginine vasopressin receptor binding increases intracellular production of cAMP and increases protein kinase A (PKA) activity. Ser256, Ser261, Ser264 and Ser269 are phosphorylated in the cytoplasmic C-terminal region of AQP2 by active PKA. Phosphorylation of at least three AQP2 monomers in each tetramer is required to start AQP2 translocation from intracellular vesicles and to cause their fusion with the apical membrane. Kidneys of animals and human neonates show a lot of morphological and functional differences. Adaptation, growth and maturation processes may be accompanied by escalation of diseases. Especially water-electrolyte imbalance can occur as a result of renal and extrarenal loss of water and electrolytes. Kidney immaturity after birth (renal narrow functional reserve and limited ability to excrete concentrated urine) favors this kind of disorders. Reduced ability to form osmotic gradient in kidney medulla as well as less efficient kidney response to vasopressin with AQP2 may cause lower capacity to save water in neonate kidneys. Role of this aquaporin in water tubular resorption in neonate is not explained but it may play the key role in this process. The renal tubular AQP2 expression in neonates is about 50% lower than in adults. In addition lower expression of V, receptors in newborn kidneys causes reduced response to AVP. Higher levels of PGE(2), lesser levels Of cAMP and restricted PKA alpha production are also observed in neonates. Moreover in neonates in comparison to adults renal AQP2 excretion do not correlate strictly with AVP concentration.
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