Disease relevance of Aqp2

• Thus, PAN-nephrosis is associated with an extensive downregulation of collecting duct water channel expression despite increased circulating vasopressin, providing an explanation for the concentrating defect associated with the nephrotic syndrome [1].
• These results indicate that age-related polyuria is associated with a downregulation of AQP2 and AQP3 expression in the medullary collecting duct, which is independent of vasopressin-mediated cAMP accumulation [2].
• Dehydration resulted in 160-200% increases of AQP-3 signal and 24-49% increases of AQP-2 signal but no change in AQP-1 signal on immunoblots of homogenates of ureters and bladders [3].
• The expression of aquaporin-2 (AQP2) is decreased in rats with bilateral ureteral obstruction (BUO) and unilateral ureteral obstruction (UUO) [4].
• Compensatory increase in AQP2, p-AQP2, and AQP3 expression in rats with diabetes mellitus [5].

Psychiatry related information on Aqp2

• On the apical side, the levels of AQP2 protein are increased in response to both arginine vasopressin and water deprivation [6].
• Vasopressin-independent regulation of collecting duct aquaporin-2 in food deprivation [7].
• Lithium, a drug for bipolar disorders, has been known to cause nephrogenic diabetes insipidus by reducing kidney-specific apical water channel, aquaporin 2 (AQP2) expression in the collecting ducts [8].

High impact information on Aqp2

• The functional expression and the limited localization of WCH-CD to the apical region of the kidney collecting tubule suggest that WCH-CD is the vasopressin-regulated water channel [9].
• Expression of WCH-CD in Xenopus oocytes markedly increases osmotic water permeability [9].
• WCH-CD is 42% identical in amino-acid sequence to CHIP28 [9].
• In these systems, the nitric oxide (NO) donors sodium nitroprusside (SNP) and NONOate and the NO synthase substrate L-arginine mimicked the effect of VP, stimulating relocation of AQP2 from cytoplasmic vesicles to the plasma membrane [10].
• SNP did not stimulate membrane insertion of AQP2 in LLC-PK1 cells expressing the phosphorylation-deficient mutant 256SerAla-AQP2, indicating that phosphorylation of Ser256 is required for signaling [10].

Chemical compound and disease context of Aqp2

• These experiments demonstrated that adriamycin-induced nephrotic syndrome is associated with marked decreases in expression of aquaporin-2, aquaporin-3, aquaporin-4, and the vasopressin-regulated urea transporter in renal inner medulla, indicative of a suppression of the capacity for water and urea absorption by the inner medullary collecting duct [11].
• Rats with Li nephropathy were treated with furosemide (3 mg/kg body weight), which blocks the activity of rBSC1, and changes in urine concentration, plasma AVP, medullary accumulation of Li ions, and apical AQP2 expression were determined [12].
• Diminished adenylate cyclase activity and aquaporin 2 expression in acute renal failure rats [13].
• Normalization of renal aquaporin-2 water channel expression by fosinopril, valsartan, and combination therapy in congestive heart failure: a new mechanism of action [14].
• To rule out a potential alteration in AQP-2 trafficking, the transport of this water channel was investigated in a group of rats subjected to dehydration, treated with desmopressin acetate (dDAVP), or water loaded [15].

Biological context of Aqp2

• Recently, we showed that inhibition of endocytosis by the cholesterol-depleting drug methyl-beta-cyclodextrin (mbetaCD) induces plasma membrane accumulation of AQP2 in transfected renal epithelial cells overexpressing epitope-tagged AQP2 [16].
• Administration of oxytocin affects vasopressin V2 receptor and aquaporin-2 gene expression in the rat [17].
• This effect on AQP2 phosphorylation was mimicked by the vasopressin (V2) agonist, 1-desamino-[8-D-arginine]vasopressin (DDAVP), or forskolin [18].
• Therefore, in addition to AQP2 and -3, AQP4 expression is also regulated by water intake [6].
• In rats with normal water supply, daily urinary excretion of AQP2 was 3.9+/-0.9% (n = 6) of total kidney expression [19].

Anatomical context of Aqp2

• Aqp2 mRNA was detected in epithelial cells after the second postnatal week and the amount significantly increased up to adulthood [20].
• Our data show that, whereas AQP9 is the main AQP of the epididymis, the mRNA specific for Aqp2, 5, 7, and 11 are also expressed in epididymal epithelial cells [20].
• Analysis of endocytic capacitance steps revealed that cAMP does not decelerate the retrieval of AQP2 from the plasma membrane [21].
• AQP-1 was localized to capillary and arteriole endothelial cells, whereas AQP-2 and -3 circumferentially lined the epithelial cell membranes except for the apical membrane of the epithelial cells adjacent to the lumens of both ureter and bladder [3].
• AQP2 mRNA expression was apparently noticed in 18-day fetuses and was enhanced gradually with age to reach a plateau at 4 wk [22].

Associations of Aqp2 with chemical compounds

• Cyclic AMP is sufficient for triggering the exocytic recruitment of aquaporin-2 in renal epithelial cells [21].
• Immunohistochemistry of the outer medulla also revealed that cisplatin decreased immunoreactivity for AQP1, AQP2, and AQP3 [23].
• Methyl-beta-cyclodextrin induces vasopressin-independent apical accumulation of aquaporin-2 in the isolated, perfused rat kidney [16].
• In conclusion, ANG II AT(1) receptor blockade in DDAVP-treated rats was associated with decreased urine concentration and decreased AQP2 and AQP1 expression [24].
• Angiotensin II AT1 receptor blockade decreases vasopressin-induced water reabsorption and AQP2 levels in NaCl-restricted rats [24].

Co-localisations of Aqp2

• Tubular renin immunostaining was apically distributed in principal cells colocalizing with aquaporin-2 in connecting tubules and cortical and medullary collecting ducts [25].

Regulatory relationships of Aqp2

• In conclusion, OT can downregulate V2R mRNA expression and upregulate AQP2 mRNA expression in the collecting duct as an agonist of the V2R like AVP [17].
• Arginine vasopressin stimulates phosphorylation of aquaporin-2 in rat renal tissue [18].
• The present results indicate that the distribution and amount of AQP-CD in the CD cells are regulated by vasopressin V2 receptor [26].
• Calmodulin inhibitors (W7 and trifluoperazine) blocked the P(f) response to vasopressin and the vasopressin-stimulated redistribution of aquaporin-2 [27].
• Opioid receptor-like 1 stimulation in the collecting duct induces aquaresis through vasopressin-independent aquaporin-2 downregulation [28].

Other interactions of Aqp2

• Four d later, the expression of AQP1, AQP2, and AQP3 proteins was determined in the kidney [23].
• Aquaporin-2 and aquaporin-3 expression was also markedly diminished in the renal cortex, indicating that the effect is not limited to the inner medullary collecting duct [11].
• Immunocytochemistry confirmed the downregulation of AQP3, AQP4, and p-AQP2 [4].
• The expression of KIM-1 and AQP-2 was similar among the treatment groups [29].
• Influence of acute elevation of plasma AVP level on rat vasopressin V2 receptor and aquaporin-2 mRNA expression [30].

Analytical, diagnostic and therapeutic context of Aqp2

• Semiquantitative immunoblotting revealed a significant increase in inner medullary AQP2 (201 +/- 12% of control rats, P < 0.05) and phosphorylated (Ser(256)) AQP2 (p-AQP2) abundance (299 +/- 32%) in DM rats [5].
• Immunoelectron microscopy further revealed an increased labeling of AQP2 in the apical plasma membrane of collecting duct principal cells (with less labeling in the intracellular vesicles) of DM rats, indicating enhanced trafficking of AQP2 to the apical plasma membrane [5].
• By immunofluorescence and electron microscopy, we show that AQP2 was shifted from a predominantly intracellular localization to the apical membrane of principal cells following 1-h perfusion of Sprague-Dawley rat kidneys with 5 mM mbetaCD [16].
• Differential centrifugation studies and immunocytochemistry in inner medullary thin sections demonstrated increased targeting of aquaporin-2 to the plasma membrane, consistent with the expected short-term action of vasopressin on aquaporin-2 trafficking [11].
• Quantification of staining revealed that the intensity of AQP2 was increased from 647+/-114 (control) to 1,968+/-299 units (mbetaCD; P<0.001), an effect similar to that seen after perfusion with 4 nM dDAVP (1,860+/-298, P<0.001) [16].

References