Pediatric Nephrology

, Volume 27, Issue 12, pp 2183–2204 | Cite as

Congenital nephrogenic diabetes insipidus: the current state of affairs

  • Daniel Wesche
  • Peter M. T. Deen
  • Nine V. A. M. Knoers


The anti-diuretic hormone arginine vasopressin (AVP) is released from the pituitary upon hypovolemia or hypernatremia, and regulates water reabsorption in the renal collecting duct principal cells. Binding of AVP to the arginine vasopressin receptor type 2 (AVPR2) in the basolateral membrane leads to translocation of aquaporin 2 (AQP2) water channels to the apical membrane of the collecting duct principal cells, inducing water permeability of the membrane. This results in water reabsorption from the pro-urine into the medullary interstitium following an osmotic gradient. Congenital nephrogenic diabetes insipidus (NDI) is a disorder associated with mutations in either the AVPR2 or AQP2 gene, causing the inability of patients to concentrate their pro-urine, which leads to a high risk of dehydration. This review focuses on the current knowledge regarding the cell biological aspects of congenital X-linked, autosomal-recessive and autosomal-dominant NDI while specifically addressing the latest developments in the field. Based on deepened mechanistic understanding, new therapeutic strategies are currently being explored, which we also discuss here.


Nephrogenic diabetes insipidus Vasopressin type-2 receptor Aquaporin-2 water channel Pharmacological chaperones 


  1. 1.
    van Lieburg AF, Knoers NV, Monnens LA (1999) Clinical presentation and follow-up of 30 patients with congenital nephrogenic diabetes insipidus. J Am Soc Nephrol 10:1958–1964PubMedGoogle Scholar
  2. 2.
    Forssman H (1955) Is hereditary diabetes insipidus of nephrogenic type associated with mental deficiency? Acta Psychiatr Neurol Scand 30:577–587PubMedCrossRefGoogle Scholar
  3. 3.
    Macaulay D, Watson M (1967) Hypernatraemia in infants as a cause of brain damage. Arch Dis Child 42:485–491PubMedCrossRefGoogle Scholar
  4. 4.
    Kanzaki S, Omura T, Miyake M, Enomoto S, Miyata I, Ishimitsu H (1985) Intracranial calcification in nephrogenic diabetes insipidus. JAMA 254:3349–3350PubMedCrossRefGoogle Scholar
  5. 5.
    Schofer O, Beetz R, Kruse K, Rascher C, Schutz C, Bohl J (1990) Nephrogenic diabetes insipidus and intracerebral calcification. Arch Dis Child 65:885–887PubMedCrossRefGoogle Scholar
  6. 6.
    Hoekstra JA, van Lieburg AF, Monnens LA, Hulstijn-Dirkmaat GM, Knoers VV (1996) Cognitive and psychosocial functioning of patients with congenital nephrogenic diabetes insipidus. Am J Med Genet 61:81–88PubMedCrossRefGoogle Scholar
  7. 7.
    Shalev H, Romanovsky I, Knoers NV, Lupa S, Landau D (2004) Bladder function impairment in aquaporin-2 defective nephrogenic diabetes insipidus. Nephrol Dial Transplant 19:608–613PubMedCrossRefGoogle Scholar
  8. 8.
    Makaryus AN, McFarlane SI (2006) Diabetes insipidus: diagnosis and treatment of a complex disease. Cleve Clin J Med 73:65–71PubMedCrossRefGoogle Scholar
  9. 9.
    Marples D, Christensen S, Christensen EI, Ottosen PD, Nielsen S (1995) Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla. J Clin Invest 95:1838–1845PubMedCrossRefGoogle Scholar
  10. 10.
    Klein JD, Gunn RB, Roberts BR, Sands JM (2002) Down-regulation of urea transporters in the renal inner medulla of lithium-fed rats. Kidney Int 61:995–1002PubMedCrossRefGoogle Scholar
  11. 11.
    Timmer RT, Sands JM (1999) Lithium intoxication. J Am Soc Nephrol 10:666–674PubMedGoogle Scholar
  12. 12.
    Trepiccione F, Christensen BM (2010) Lithium-induced nephrogenic diabetes insipidus: new clinical and experimental findings. J Nephrol 23(Suppl 16):S43–S48PubMedGoogle Scholar
  13. 13.
    Amlal H, Krane CM, Chen Q, Soleimani M (2000) Early polyuria and urinary concentrating defect in potassium deprivation. Am J Physiol Renal Physiol 279:F655–F663PubMedGoogle Scholar
  14. 14.
    Elkjaer M-L, Kwon T-H, Wang W, Nielsen J, Knepper MA, Frøkiaer J, Nielsen S (2002) Altered expression of NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats. Am J Physiol Renal Physiol 283:F1376–F1388PubMedGoogle Scholar
  15. 15.
    Wang W, Li C, Kwon T-H, Miller RT, Knepper M, Frøkiaer J, Nielsen S (2004) Reduced expression of renal Na+ transporters in rates with PTH-induced hypercalcemia. Am J Physiol Renal Physiol 286:F535–F545Google Scholar
  16. 16.
    Earm JH, Christensen BM, Frokiaer J, Marples D, Han JS, Knepper MA, Nielsen S (1998) Decreased aquaporin-2 expression and apical plasma membrane delivery in kidney collecting ducts of polyuric hypercalcemic rats. J Am Soc Nephrol 9:2181–2193PubMedGoogle Scholar
  17. 17.
    Sands JM, Naruse M, Jacobs JD, Wilcox JN, Klein JD (1996) Changes in aquaporin-2 protein contribute to the urine concentrating defect in rats fed a low-protein diet. J Clin Invest 97:2807–2814PubMedCrossRefGoogle Scholar
  18. 18.
    Frokiaer J, Li C, Shi Y, Jensen A, Praetorius H, Hansen H, Topcu O, Sardeli C, Wang W, Kwon TH, Nielsen S (2003) Renal aquaporins and sodium transporters with special focus on urinary tract obstruction. APMIS Suppl:71–79Google Scholar
  19. 19.
    Frokiaer J, Marples D, Knepper MA, Nielsen S (1996) Bilateral ureteral obstruction downregulates expression of vasopressin-sensitive AQP-2 water channel in rat kidney. Am J Physiol 270:F657–F668PubMedGoogle Scholar
  20. 20.
    Garofeanu CG, Weir M, Rosas-Arellano MP, Henson G, Garg AX, Clark WF (2005) Causes of reversible nephrogenic diabetes insipidus: a systematic review. Am J Kidney Dis 45:626–637PubMedCrossRefGoogle Scholar
  21. 21.
    Brandis K (2011) Fluid physiology - Section 3.1: Water turnover. URL:
  22. 22.
    Trachtman H (2009) Sodium and water. In: Avner ED, Harmon WE, Niaudet P, Yoshikawa N (eds) Pediatr nephrol, 6th edn. Springer, Berlin Heidelberg New York, pp 159–184Google Scholar
  23. 23.
    Sachs H, Takabatake Y (1964) Evidence for a precursor in vasopressin biosynthesis. Endocrinol 75:943–948CrossRefGoogle Scholar
  24. 24.
    Nossent AY, Robben JH, Deen PM, Vos HL, Rosendaal FR, Doggen CJ, Hansen JL, Sheikh SP, Bertina RM, Eikenboom JC (2010) Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels. J Thromb Haemost 8:1547–1554PubMedCrossRefGoogle Scholar
  25. 25.
    Loonen AJ, Knoers NV, van Os CH, Deen PM (2008) Aquaporin 2 mutations in nephrogenic diabetes insipidus. Semin Nephrol 28:252–265PubMedCrossRefGoogle Scholar
  26. 26.
    Hendriks G, Koudijs M, van Balkom BW, Oorschot V, Klumperman J, Deen PM, van der Sluijs P (2004) Glycosylation is important for cell surface expression of the water channel aquaporin-2 but is not essential for tetramerization in the endoplasmic reticulum. J Biol Chem 279:2975–2983PubMedCrossRefGoogle Scholar
  27. 27.
    Nielsen S, DiGiovanni SR, Christensen EI, Knepper MA, Harris HW (1993) Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci USA 90:11663–11667PubMedCrossRefGoogle Scholar
  28. 28.
    Kamsteeg EJ, Heijnen I, van Os CH, Deen PM (2000) The subcellular localization of an aquaporin-2 tetramer depends on the stoichiometry of phosphorylated and nonphosphorylated monomers. J Cell Biol 151:919–930PubMedCrossRefGoogle Scholar
  29. 29.
    Mandon B, Chou CL, Nielsen S, Knepper MA (1996) Syntaxin-4 is localized to the apical plasma membrane of rat renal collecting duct cells: possible role in aquaporin-2 trafficking. J Clin Invest 98:906–913PubMedCrossRefGoogle Scholar
  30. 30.
    Kanehisa M, Goto S (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30PubMedCrossRefGoogle Scholar
  31. 31.
    Kanehisa M, Goto S, Hattori M, Aoki-Kinoshita KF, Itoh M, Kawashima S, Katayama T, Araki M, Hirakawa M (2006) From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res 34:D354–D357PubMedCrossRefGoogle Scholar
  32. 32.
    Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M (2010) KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res 38:D355–D360PubMedCrossRefGoogle Scholar
  33. 33.
    Teng FY, Wang Y, Tang BL (2001) The syntaxins. Genome Biol 2:REVIEWS3012Google Scholar
  34. 34.
    Nielsen S, Marples D, Birn H, Mohtashami M, Dalby NO, Trimble M, Knepper M (1995) Expression of VAMP-2-like protein in kidney collecting duct intracellular vesicles. Colocalization with Aquaporin-2 water channels. J Clin Invest 96:1834–1844PubMedCrossRefGoogle Scholar
  35. 35.
    Schroer TA (2004) Dynactin. Annu Rev Cell Dev Biol 20:759–779PubMedCrossRefGoogle Scholar
  36. 36.
    Lee YJ, Kwon TH (2009) Ubiquitination of aquaporin-2 in the kidney. Electrolyte Blood Press 7:1–4PubMedCrossRefGoogle Scholar
  37. 37.
    Vossenkamper A, Nedvetsky PI, Wiesner B, Furkert J, Rosenthal W, Klussmann E (2007) Microtubules are needed for the perinuclear positioning of aquaporin-2 after its endocytic retrieval in renal principal cells. Am J Physiol Cell Physiol 293:C1129–C1138PubMedCrossRefGoogle Scholar
  38. 38.
    Marples D, Schroer TA, Ahrens N, Taylor A, Knepper MA, Nielsen S (1998) Dynein and dynactin colocalize with AQP2 water channels in intracellular vesicles from kidney collecting duct. Am J Physiol 274:F384–F394PubMedGoogle Scholar
  39. 39.
    Palamidessi A, Frittoli E, Garre M, Faretta M, Mione M, Testa I, Diaspro A, Lanzetti L, Scita G, Di Fiore PP (2008) Endocytic trafficking of Rac is required for the spatial restriction of signaling in cell migration. Cell 134:135–147PubMedCrossRefGoogle Scholar
  40. 40.
    Stenmark H (2009) Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 10:513–525PubMedCrossRefGoogle Scholar
  41. 41.
    Kamsteeg EJ, Hendriks G, Boone M, Konings IB, Oorschot V, van der Sluijs P, Klumperman J, Deen PM (2006) Short-chain ubiquitination mediates the regulated endocytosis of the aquaporin-2 water channel. Proc Natl Acad Sci USA 103:18344–18349PubMedCrossRefGoogle Scholar
  42. 42.
    Klussmann E, Tamma G, Lorenz D, Wiesner B, Maric K, Hofmann F, Aktories K, Valenti G, Rosenthal W (2001) An inhibitory role of Rho in the vasopressin-mediated translocation of aquaporin-2 into cell membranes of renal principal cells. J Biol Chem 276:20451–20457PubMedCrossRefGoogle Scholar
  43. 43.
    Tajika Y, Matsuzaki T, Suzuki T, Ablimit A, Aoki T, Hagiwara H, Kuwahara M, Sasaki S, Takata K (2005) Differential regulation of AQP2 trafficking in endosomes by microtubules and actin filaments. Histochem Cell Biol 124:1–12PubMedCrossRefGoogle Scholar
  44. 44.
    Yasui M, Zelenin SM, Celsi G, Aperia A (1997) Adenylate cyclase-coupled vasopressin receptor activates AQP2 promoter via a dual effect on CRE and AP1 elements. Am J Physiol 272:F443–F450PubMedGoogle Scholar
  45. 45.
    Nielsen S, Kwon TH, Christensen BM, Promeneur D, Frokiaer J, Marples D (1999) Physiology and pathophysiology of renal aquaporins. J Am Soc Nephrol 10:647–663PubMedGoogle Scholar
  46. 46.
    Blanchard A, Frank M, Wuerzner G, Peyrard S, Bankir L, Jeunemaitre X, Azizi M (2011) Antinatriuretic effect of vasopressin in humans is amiloride-sensitive, thus ENaC dependent. Clin J Am Soc Nephrol 6:753–759PubMedCrossRefGoogle Scholar
  47. 47.
    Stockand JD (2010) Vasopressin regulation of renal sodium excretion. Kidney Int 78:849–856PubMedCrossRefGoogle Scholar
  48. 48.
    Sands JM (2003) Molecular mechanisms of urea transport. J Membr Biol 191:149–163PubMedCrossRefGoogle Scholar
  49. 49.
    Brown D, Katsura T, Gustafson CE (1998) Cellular mechanisms of aquaporin trafficking. Am J Physiol 275:F328–F331PubMedGoogle Scholar
  50. 50.
    Sands JM, Bichet DG (2006) Nephrogenic diabetes insipidus. Ann Intern Med 144:186–194PubMedGoogle Scholar
  51. 51.
    Birnbaumer M (2001) The V2 vasopressin receptor mutations and fluid homeostasis. Cardiovasc Res 51:409–415PubMedCrossRefGoogle Scholar
  52. 52.
    van den Ouweland AM, Dreesen JC, Verdijk M, Knoers NV, Monnens LA, Rocchi M, van Oost BA (1992) Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus. Nat Genet 2:99–102PubMedCrossRefGoogle Scholar
  53. 53.
    Bichet DG (2008) Vasopressin receptor mutations in nephrogenic diabetes insipidus. Semin Nephrol 28:245–251PubMedCrossRefGoogle Scholar
  54. 54.
    Nomura Y, Onigata K, Nagashima T, Yutani S, Mochizuki H, Nagashima K, Morikawa A (1997) Detection of skewed X-inactivation in two female carriers of vasopressin type 2 receptor gene mutation. J Clin Endocrinol Metab 82:3434–3437PubMedCrossRefGoogle Scholar
  55. 55.
    Faerch M, Corydon TJ, Rittig S, Christensen JH, Hertz JM, Jendle J (2010) Skewed X-chromosome inactivation causing diagnostic misinterpretation in congenital nephrogenic diabetes insipidus. Scand J Urol Nephrol 44:324–330PubMedCrossRefGoogle Scholar
  56. 56.
    Firsov D, Mandon B, Morel A, Merot J, Le Maout S, Bellanger AC, de Rouffignac C, Elalouf JM, Buhler JM (1994) Molecular analysis of vasopressin receptors in the rat nephron. Evidence for alternative splicing of the V2 receptor. Pflug Arch 429:79–89CrossRefGoogle Scholar
  57. 57.
    Boeckmann B, Bairoch A, Apweiler R, Blatter MC, Estreicher A, Gasteiger E, Martin MJ, Michoud K, O'Donovan C, Phan I, Pilbout S, Schneider M (2003) The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res 31:365–370PubMedCrossRefGoogle Scholar
  58. 58.
    Brown CA, Black SD (1989) Membrane topology of mammalian cytochromes P-450 from liver endoplasmic reticulum. Determination by trypsinolysis of phenobarbital-treated microsomes. J Biol Chem 264:4442–4449PubMedGoogle Scholar
  59. 59.
    Hartmann E, Rapoport TA, Lodish HF (1989) Predicting the orientation of eukaryotic membrane-spanning proteins. Proc Natl Acad Sci USA 86:5786–5790PubMedCrossRefGoogle Scholar
  60. 60.
    Conner M, Hawtin SR, Simms J, Wootten D, Lawson Z, Conner AC, Parslow RA, Wheatley M (2007) Systematic analysis of the entire second extracellular loop of the V(1a) vasopressin receptor: key residues, conserved throughout a G-protein-coupled receptor family, identified. J Biol Chem 282:17405–17412PubMedCrossRefGoogle Scholar
  61. 61.
    Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289:739–745PubMedCrossRefGoogle Scholar
  62. 62.
    Sangkuhl K, Rompler H, Busch W, Karges B, Schoneberg T (2005) Nephrogenic diabetes insipidus caused by mutation of Tyr205: a key residue of V2 vasopressin receptor function. Hum Mutat 25:505PubMedCrossRefGoogle Scholar
  63. 63.
    Oksche A, Schulein R, Rutz C, Liebenhoff U, Dickson J, Muller H, Birnbaumer M, Rosenthal W (1996) Vasopressin V2 receptor mutants that cause X-linked nephrogenic diabetes insipidus: analysis of expression, processing, and function. Mol Pharmacol 50:820–828PubMedGoogle Scholar
  64. 64.
    Sadeghi H, Birnbaumer M (1999) O-Glycosylation of the V2 vasopressin receptor. Glycobiology 9:731–737PubMedCrossRefGoogle Scholar
  65. 65.
    Robben JH, Knoers NV, Deen PM (2004) Regulation of the vasopressin V2 receptor by vasopressin in polarized renal collecting duct cells. Mol Biol Cell 15:5693–5699PubMedCrossRefGoogle Scholar
  66. 66.
    Sarmiento JM, Anazco CC, Campos DM, Prado GN, Navarro J, Gonzalez CB (2004) Novel down-regulatory mechanism of the surface expression of the vasopressin V2 receptor by an alternative splice receptor variant. J Biol Chem 279:47017–47023PubMedCrossRefGoogle Scholar
  67. 67.
    Gonzalez A, Borquez M, Trigo CA, Brenet M, Sarmiento JM, Figueroa CD, Navarro J, Gonzalez CB (2011) The splice variant of the V2 vasopressin receptor adopts alternative topologies. Biochem 50:4981–4986CrossRefGoogle Scholar
  68. 68.
    Bichet DG, Bouvier M, Chini B, Serradeil-Le Gal C, Gimpl G, Guillon G, Kimura T, Knepper MA, Lolait S, Manning M, Mouillac B, Verbalis JG, Wheatley M, Zingg HH (2011) Vasopressin and oxytocin receptors: V2. Last modified on 2010-07-01. Accessed on 2011-09-10. IUPHAR database (IUPHAR-DB),
  69. 69.
    Thibonnier M, Preston JA, Dulin N, Wilkins PL, Berti-Mattera LN, Mattera R (1997) The human V3 pituitary vasopressin receptor: ligand binding profile and density-dependent signaling pathways. Endocrinol 138:4109–4122CrossRefGoogle Scholar
  70. 70.
    Vargas-Poussou R, Forestier L, Dautzenberg MD, Niaudet P, Dechaux M, Antignac C (1997) Mutations in the vasopressin V2 receptor and aquaporin-2 genes in 12 families with congenital nephrogenic diabetes insipidus. J Am Soc Nephrol 8:1855–1862PubMedGoogle Scholar
  71. 71.
    Spanakis E, Milord E, Gragnoli C (2008) AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance. J Cell Physiol 217:605–617PubMedCrossRefGoogle Scholar
  72. 72.
    Krawczak M, Cooper DN (1997) The human gene mutation database. Trends Genet 13:121–122PubMedCrossRefGoogle Scholar
  73. 73.
    Krawczak M, Ball EV, Cooper DN (1998) Neighboring-nucleotide effects on the rates of germ-line single-base-pair substitution in human genes. Am J Hum Genet 63:474–488PubMedCrossRefGoogle Scholar
  74. 74.
    Wenkert D, Schoneberg T, Merendino JJ Jr, Rodriguez Pena MS, Vinitsky R, Goldsmith PK, Wess J, Spiegel AM (1996) Functional characterization of five V2 vasopressin receptor gene mutations. Mol Cell Endocrinol 124:43–50PubMedCrossRefGoogle Scholar
  75. 75.
    Abaci A, Wood K, Demir K, Buyukgebiz A, Bober E, Kopp P (2010) A novel mutation in the AVPR2 gene (222delA) associated with X-linked nephrogenic diabetes insipidus in a boy with growth failure. Endocr Pract 16:231–236PubMedCrossRefGoogle Scholar
  76. 76.
    Moon SD, Kim JH, Shim JY, Lim DJ, Cha BY, Han JH (2011) Analysis of a novel AVPR2 mutation in a family with nephrogenic diabetes insipidus. Int J Clin Exp Med 4:1–9PubMedGoogle Scholar
  77. 77.
    Fujimoto M, Imai K, Hirata K, Kashiwagi R, Morinishi Y, Kitazawa K, Sasaki S, Arinami T, Nonoyama S, Noguchi E (2008) Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes. BMC Med Genet 9:42PubMedCrossRefGoogle Scholar
  78. 78.
    Satoh M, Ogikubo S, Yoshizawa-Ogasawara A (2008) Correlation between clinical phenotypes and X-inactivation patterns in six female carriers with heterozygote vasopressin type 2 receptor gene mutations. Endocr J 55:277–284PubMedCrossRefGoogle Scholar
  79. 79.
    Sakallioglu O, Tascilar ME, Kalman S, Cheong HI, Atay AA (2009) Nephrogenic diabetes insipidus due to a novel AVPR2 mutation. J Pediatr Endocrinol Metab 22:187–189PubMedCrossRefGoogle Scholar
  80. 80.
    Ranadive SA, Ersoy B, Favre H, Cheung CC, Rosenthal SM, Miller WL, Vaisse C (2009) Identification, characterization and rescue of a novel vasopressin-2 receptor mutation causing nephrogenic diabetes insipidus. Clin Endocrinol (Oxf) 71:388–393CrossRefGoogle Scholar
  81. 81.
    Vaisbich MH, Carneiro J, Boson W, Resende B, De ML, Honjo RS, Kim CA, Koch VH (2009) Nephrogenic diabetes insipidus (NDI): clinical, laboratory and genetic characterization of five Brazilian patients. Clinics(Sao Paulo) 64:409–414Google Scholar
  82. 82.
    Takatani T, Matsuo K, Kinoshita K, Takatani R, Minagawa M, Kohno Y (2010) A novel missense mutation in the AVPR2 gene of a Japanese infant with nephrogenic diabetes insipidus. J Pediatr Endocrinol Metab 23:415–418PubMedCrossRefGoogle Scholar
  83. 83.
    El-Kares R, Hueber PA, Blumenkrantz M, Iglesias D, Ma K, Jabado N, Bichet DG, Goodyer P (2009) Wilms tumor arising in a child with X-linked nephrogenic diabetes insipidus. Pediatr Nephrol 24:1313–1319PubMedCrossRefGoogle Scholar
  84. 84.
    Sahakitrungruang T, Tee MK, Rattanachartnarong N, Shotelersuk V, Suphapeetiporn K, Miller WL (2010) Functional characterization of vasopressin receptor 2 mutations causing partial and complete congenital nephrogenic diabetes insipidus in Thai families. Horm Res Paediatr 73:349–354PubMedCrossRefGoogle Scholar
  85. 85.
    Oksche A, Dickson J, Schulein R, Seyberth HW, Muller M, Rascher W, Birnbaumer M, Rosenthal W (1994) Two novel mutations in the vasopressin V2 receptor gene in patients with congenital nephrogenic diabetes insipidus. Biochem Biophys Res Comm 205:552–557PubMedCrossRefGoogle Scholar
  86. 86.
    Welsh MJ, Smith AE (1993) Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis. Cell 73:1251–1254PubMedCrossRefGoogle Scholar
  87. 87.
    Tsukaguchi H, Matsubara H, Taketani S, Mori Y, Seido T, Inada M (1995) Binding-, intracellular transport-, and biosynthesis-defective mutants of vasopressin type 2 receptor in patients with X-linked nephrogenic diabetes insipidus. J Clin Invest 96:2043–2050PubMedCrossRefGoogle Scholar
  88. 88.
    Ala Y, Morin D, Mouillac B, Sabatier N, Vargas R, Cotte N, Dechaux M, Antignac C, Arthus MF, Lonergan M, Turner MS, Balestre MN, Alonso G, Hibert M, Barberis C, Hendy GN, Bichet DG, Jard S (1998) Functional studies of twelve mutant V2 vasopressin receptors related to nephrogenic diabetes insipidus: molecular basis of a mild clinical phenotype. J Am Soc Nephrol 9:1861–1872PubMedGoogle Scholar
  89. 89.
    Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S (1994) Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus. Am J Hum Genet 55:278–286PubMedGoogle Scholar
  90. 90.
    Morello JP, Bichet DG (2001) Nephrogenic diabetes insipidus. Annu Rev Physiol 63:607–630PubMedCrossRefGoogle Scholar
  91. 91.
    Arthus MF, Lonergan M, Crumley MJ, Naumova AK, Morin D, De Marco LA, Kaplan BS, Robertson GL, Sasaki S, Morgan K, Bichet DG, Fujiwara TM (2000) Report of 33 novel AVPR2 mutations and analysis of 117 families with X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 11:1044–1054PubMedGoogle Scholar
  92. 92.
    Ellgaard L, Helenius A (2001) ER quality control: towards an understanding at the molecular level. Curr Opin Cell Biol 13:431–437PubMedCrossRefGoogle Scholar
  93. 93.
    Oueslati M, Hermosilla R, Schonenberger E, Oorschot V, Beyermann M, Wiesner B, Schmidt A, Klumperman J, Rosenthal W, Schulein R (2007) Rescue of a nephrogenic diabetes insipidus-causing vasopressin V2 receptor mutant by cell-penetrating peptides. J Biol Chem 282:20676–20685PubMedCrossRefGoogle Scholar
  94. 94.
    Pan Y, Wilson P, Gitschier J (1994) The effect of eight V2 vasopressin receptor mutations on stimulation of adenylyl cyclase and binding to vasopressin. J Biol Chem 269:31933–31937PubMedGoogle Scholar
  95. 95.
    Robben JH, Knoers NV, Deen PM (2006) Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 291:F257–F270PubMedCrossRefGoogle Scholar
  96. 96.
    Barak LS, Oakley RH, Laporte SA, Caron MG (2001) Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus. Proc Natl Acad Sci USA 98:93–98PubMedCrossRefGoogle Scholar
  97. 97.
    Knoers N, Monnens LA (1992) Nephrogenic diabetes insipidus: clinical symptoms, pathogenesis, genetics and treatment. Pediatr Nephrol 6:476–482PubMedCrossRefGoogle Scholar
  98. 98.
    Bai L, Fushimi K, Sasaki S, Marumo F (1996) Structure of aquaporin-2 vasopressin water channel. J Biol Chem 271:5171–5176PubMedCrossRefGoogle Scholar
  99. 99.
    Marr N, Bichet DG, Hoefs S, Savelkoul PJ, Konings IB, De MF, Graat MP, Arthus MF, Lonergan M, Fujiwara TM, Knoers NV, Landau D, Balfe WJ, Oksche A, Rosenthal W, Muller D, van Os CH, Deen PM (2002) Cell-biologic and functional analyses of five new Aquaporin-2 missense mutations that cause recessive nephrogenic diabetes insipidus. J Am Soc Nephrol 13:2267–2277PubMedCrossRefGoogle Scholar
  100. 100.
    Baumgarten R, Van De Pol MH, Wetzels JF, van Os CH, Deen PM (1998) Glycosylation is not essential for vasopressin-dependent routing of aquaporin-2 in transfected Madin-Darby canine kidney cells. J Am Soc Nephrol 9:1553–1559PubMedGoogle Scholar
  101. 101.
    Fushimi K, Sasaki S, Marumo F (1997) Phosphorylation of serine 256 is required for cAMP-dependent regulatory exocytosis of the aquaporin-2 water channel. J Biol Chem 272:14800–14804PubMedCrossRefGoogle Scholar
  102. 102.
    Hoffert JD, Pisitkun T, Wang G, Shen RF, Knepper MA (2006) Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites. Proc Natl Acad Sci USA 103:7159–7164PubMedCrossRefGoogle Scholar
  103. 103.
    Hoffert JD, Fenton RA, Moeller HB, Simons B, Tchapyjnikov D, McDill BW, Yu MJ, Pisitkun T, Chen F, Knepper MA (2008) Vasopressin-stimulated increase in phosphorylation at Ser269 potentiates plasma membrane retention of aquaporin-2. J Biol Chem 283:24617–24627PubMedCrossRefGoogle Scholar
  104. 104.
    Moeller HB, MacAulay N, Knepper MA, Fenton RA (2009) Role of multiple phosphorylation sites in the COOH-terminal tail of aquaporin-2 for water transport: evidence against channel gating. Am J Physiol Renal Physiol 296:F649–F657PubMedCrossRefGoogle Scholar
  105. 105.
    Xie L, Hoffert JD, Chou CL, Yu MJ, Pisitkun T, Knepper MA, Fenton RA (2010) Quantitative analysis of aquaporin-2 phosphorylation. Am J Physiol Renal Physiol 298:F1018–F1023PubMedCrossRefGoogle Scholar
  106. 106.
    Hoffert JD, Nielsen J, Yu MJ, Pisitkun T, Schleicher SM, Nielsen S, Knepper MA (2007) Dynamics of aquaporin-2 serine-261 phosphorylation in response to short-term vasopressin treatment in collecting duct. Am J physiology Renal Physiol 292:F691–F700CrossRefGoogle Scholar
  107. 107.
    Moeller HB, Olesen ET, Fenton RA (2011) Regulation of the water channel aquaporin-2 by posttranslational modification. Am J Physiol Renal Physiol 300:F1062–F1073PubMedCrossRefGoogle Scholar
  108. 108.
    Heymann JB, Engel A (1999) Aquaporins: Phylogeny, Structure, and Physiology of Water Channels. News Physiol Sci 14:187–193PubMedGoogle Scholar
  109. 109.
    Hub JS, Grubmuller H, de Groot BL (2009) Dynamics and energetics of permeation through aquaporins. What do we learn from molecular dynamics simulations? Handb Exp Pharmacol 57–76Google Scholar
  110. 110.
    de Groot BL, Grubmuller H (2001) Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF. Science 294:2353–2357PubMedCrossRefGoogle Scholar
  111. 111.
    Kozono D, Yasui M, King LS, Agre P (2002) Aquaporin water channels: atomic structure molecular dynamics meet clinical medicine. J Clin Invest 109:1395–1399PubMedGoogle Scholar
  112. 112.
    Murata K, Mitsuoka K, Hirai T, Walz T, Agre P, Heymann JB, Engel A, Fujiyoshi Y (2000) Structural determinants of water permeation through aquaporin-1. Nature 407:599–605PubMedCrossRefGoogle Scholar
  113. 113.
    de Groot BL, Grubmuller H (2005) The dynamics and energetics of water permeation and proton exclusion in aquaporins. Curr Opin Struct Biol 15:176–183PubMedCrossRefGoogle Scholar
  114. 114.
    Lin SH, Bichet DG, Sasaki S, Kuwahara M, Arthus MF, Lonergan M, Lin YF (2002) Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes insipidus in Chinese families. J Clin Endocrinol Metab 87:2694–2700PubMedCrossRefGoogle Scholar
  115. 115.
    Boone M, Deen PM (2009) Congenital nephrogenic diabetes insipidus: what can we learn from mouse models? Exp Physiol 94:186–190PubMedCrossRefGoogle Scholar
  116. 116.
    Lloyd DJ, Hall FW, Tarantino LM, Gekakis N (2005) Diabetes insipidus in mice with a mutation in aquaporin-2. PLoS Genet 1:e20PubMedCrossRefGoogle Scholar
  117. 117.
    Tamarappoo BK, Verkman AS (1998) Defective aquaporin-2 trafficking in nephrogenic diabetes insipidus and correction by chemical chaperones. J Clin Invest 101:2257–2267PubMedCrossRefGoogle Scholar
  118. 118.
    Abrami L, Berthonaud V, Deen PM, Rousselet G, Tacnet F, Ripoche P (1996) Glycerol permeability of mutant aquaporin 1 and other AQP-MIP proteins: inhibition studies. Pflug Arch 431:408–414CrossRefGoogle Scholar
  119. 119.
    Goji K, Kuwahara M, Gu Y, Matsuo M, Marumo F, Sasaki S (1998) Novel mutations in aquaporin-2 gene in female siblings with nephrogenic diabetes insipidus: evidence of disrupted water channel function. J Clin Endocrinol Metab 83:3205–3209PubMedCrossRefGoogle Scholar
  120. 120.
    Kamsteeg EJ, Deen PM (2000) Importance of aquaporin-2 expression levels in genotype -phenotype studies in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 279:F778–F784PubMedGoogle Scholar
  121. 121.
    Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS (2001) Neonatal mortality in an aquaporin-2 knock-in mouse model of recessive nephrogenic diabetes insipidus. J Biol Chem 276:2775–2779PubMedCrossRefGoogle Scholar
  122. 122.
    Deen PM, van Balkom BW, Kamsteeg EJ (2000) Routing of the aquaporin-2 water channel in health and disease. Eur J Cell Biol 79:523–530PubMedCrossRefGoogle Scholar
  123. 123.
    De Mattia F, Savelkoul PJ, Kamsteeg EJ, Konings IB, van der Sluijs P, Mallmann R, Oksche A, Deen PM (2005) Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus. J Am Soc Nephrol 16:2872–2880PubMedCrossRefGoogle Scholar
  124. 124.
    Kamsteeg EJ, Bichet DG, Konings IB, Nivet H, Lonergan M, Arthus MF, van Os CH, Deen PM (2003) Reversed polarized delivery of an aquaporin-2 mutant causes dominant nephrogenic diabetes insipidus. J Cell Biol 163:1099–1109PubMedCrossRefGoogle Scholar
  125. 125.
    Kuwahara M, Iwai K, Ooeda T, Igarashi T, Ogawa E, Katsushima Y, Shinbo I, Uchida S, Terada Y, Arthus MF, Lonergan M, Fujiwara TM, Bichet DG, Marumo F, Sasaki S (2001) Three families with autosomal dominant nephrogenic diabetes insipidus caused by aquaporin-2 mutations in the C-terminus. Am J Hum Genet 69:738–748PubMedCrossRefGoogle Scholar
  126. 126.
    Marr N, Bichet DG, Lonergan M, Arthus MF, Jeck N, Seyberth HW, Rosenthal W, van Os CH, Oksche A, Deen PM (2002) Heteroligomerization of an Aquaporin-2 mutant with wild-type Aquaporin-2 and their misrouting to late endosomes/lysosomes explains dominant nephrogenic diabetes insipidus. Hum Mol Genet 11:779–789PubMedCrossRefGoogle Scholar
  127. 127.
    Mulders SM, Bichet DG, Rijss JP, Kamsteeg EJ, Arthus MF, Lonergan M, Fujiwara M, Morgan K, Leijendekker R, van der Sluijs P, van Os CH, Deen PM (1998) An aquaporin-2 water channel mutant which causes autosomal dominant nephrogenic diabetes insipidus is retained in the Golgi complex. J Clin Invest 102:57–66PubMedCrossRefGoogle Scholar
  128. 128.
    Savelkoul PJ, De MF, Li Y, Kamsteeg EJ, Konings IB, van der Sluijs P, Deen PM (2009) p.R254Q mutation in the aquaporin-2 water channel causing dominant nephrogenic diabetes insipidus is due to a lack of arginine vasopressin-induced phosphorylation. Hum Mutat 30:E891–E903PubMedCrossRefGoogle Scholar
  129. 129.
    Shinbo I, Fushimi K, Kasahara M, Yamauchi K, Sasaki S, Marumo F (1999) Functional analysis of aquaporin-2 mutants associated with nephrogenic diabetes insipidus by yeast expression. Am J Physiol 277:F734–F741PubMedGoogle Scholar
  130. 130.
    Kamsteeg EJ, Wormhoudt TA, Rijss JP, van Os CH, Deen PM (1999) An impaired routing of wild-type aquaporin-2 after tetramerization with an aquaporin-2 mutant explains dominant nephrogenic diabetes insipidus. EMBO J 18:2394–2400PubMedCrossRefGoogle Scholar
  131. 131.
    Moon SS, Kim HJ, Choi YK, Seo HA, Jeon JH, Lee JE, Lee JY, Kwon TH, Kim JG, Kim BW, Lee IK (2009) Novel mutation of aquaporin-2 gene in a patient with congenital nephrogenic diabetes insipidus. Endocr J 56:905–910PubMedCrossRefGoogle Scholar
  132. 132.
    van Lieburg AF, Verdijk MA, Knoers VV, van Essen AJ, Proesmans W, Mallmann R, Monnens LA, van Oost BA, van Os CH, Deen PM (1994) Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene. AmJ Hum Genet 55:648–652Google Scholar
  133. 133.
    Asai T, Kuwahara M, Kurihara H, Sakai T, Terada Y, Marumo F, Sasaki S (2003) Pathogenesis of nephrogenic diabetes insipidus by aquaporin-2 C-terminus mutations. Kidney Int 64:2–10PubMedCrossRefGoogle Scholar
  134. 134.
    van Balkom BW, Savelkoul PJ, Markovich D, Hofman E, Nielsen S, van der Sluijs P, Deen PM (2002) The role of putative phosphorylation sites in the targeting and shuttling of the aquaporin-2 water channel. J Biol Chem 277:41473–41479PubMedCrossRefGoogle Scholar
  135. 135.
    Lu HJ, Matsuzaki T, Bouley R, Hasler U, Qin QH, Brown D (2008) The phosphorylation state of serine 256 is dominant over that of serine 261 in the regulation of AQP2 trafficking in renal epithelial cells. Am J Physiol Renal Physiol 295:F290–F294PubMedCrossRefGoogle Scholar
  136. 136.
    Moeller HB, MacAulay N, Knepper MA, Fenton RA (2009) Role of multiple phosphorylation sites in the COOH-terminal tail of aquaporin-2 for water transport: evidence against channel gating. Am J Physiol Renal Physiol 296:F649–F657PubMedCrossRefGoogle Scholar
  137. 137.
    Kamsteeg EJ, Stoffels M, Tamma G, Konings IB, Deen PM (2009) Repulsion between Lys258 and upstream arginines explains the missorting of the AQP2 mutant p.Glu258Lys in nephrogenic diabetes insipidus. Hum Mutat 30:1387–1396PubMedCrossRefGoogle Scholar
  138. 138.
    Kamsteeg EJ, Savelkoul PJ, Hendriks G, Konings IB, Nivillac NM, Lagendijk AK, van der Sluijs P, Deen PM (2008) Missorting of the Aquaporin-2 mutant E258K to multivesicular bodies/lysosomes in dominant NDI is associated with its monoubiquitination and increased phosphorylation by PKC but is due to the loss of E258. Pflug Arch 455:1041–1054CrossRefGoogle Scholar
  139. 139.
    Tajika Y, Matsuzaki T, Suzuki T, Aoki T, Hagiwara H, Tanaka S, Kominami E, Takata K (2002) Immunohistochemical characterization of the intracellular pool of water channel aquaporin-2 in the rat kidney. Anat Sci Int 77:189–195PubMedCrossRefGoogle Scholar
  140. 140.
    Sohara E, Rai T, Yang SS, Uchida K, Nitta K, Horita S, Ohno M, Harada A, Sasaki S, Uchida S (2006) Pathogenesis and treatment of autosomal-dominant nephrogenic diabetes insipidus caused by an aquaporin 2 mutation. Proc Natl Acad Sci USA 103:14217–14222PubMedCrossRefGoogle Scholar
  141. 141.
    Katsura T, Gustafson CE, Ausiello DA, Brown D (1997) Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells. Am J Physiol 272:F817–F822PubMedGoogle Scholar
  142. 142.
    Edemir B, Pavenstadt H, Schlatter E, Weide T (2011) Mechanisms of cell polarity and aquaporin sorting in the nephron. Pflug Arch 461:607–621CrossRefGoogle Scholar
  143. 143.
    McDill BW, Li SZ, Kovach PA, Ding L, Chen F (2006) Congenital progressive hydronephrosis (cph) is caused by an S256L mutation in aquaporin-2 that affects its phosphorylation and apical membrane accumulation. Proc Natl Acad Sci USA 103:6952–6957PubMedCrossRefGoogle Scholar
  144. 144.
    Rojek A, Fuchtbauer EM, Kwon TH, Frokiaer J, Nielsen S (2006) Severe urinary concentrating defect in renal collecting duct-selective AQP2 conditional-knockout mice. Proc Natl Acad Sci USA 103:6037–6042PubMedCrossRefGoogle Scholar
  145. 145.
    Yang B, Zhao D, Qian L, Verkman AS (2006) Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion. Am J Physiol Renal Physiol 291:F465–F472PubMedCrossRefGoogle Scholar
  146. 146.
    De Mattia F, Savelkoul PJ, Bichet DG, Kamsteeg EJ, Konings IB, Marr N, Arthus MF, Lonergan M, van Os CH, van der Sluijs P, Robertson G, Deen PM (2004) A novel mechanism in recessive nephrogenic diabetes insipidus: wild-type aquaporin-2 rescues the apical membrane expression of intracellularly retained AQP2-P262L. Hum Mol Genet 13:3045–3056PubMedCrossRefGoogle Scholar
  147. 147.
    Deen PM (2007) Mouse models for congenital nephrogenic diabetes insipidus: what can we learn from them? Nephrol Dial Transplant 22:1023–1026PubMedCrossRefGoogle Scholar
  148. 148.
    Kirchlechner V, Koller DY, Seidl R, Waldhauser F (1999) Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride. Arch Dis Child 80:548–552PubMedCrossRefGoogle Scholar
  149. 149.
    Alon U, Chan JC (1985) Hydrochlorothiazide-amiloride in the treatment of congenital nephrogenic diabetes insipidus. Am J Nephrol 5:9–13PubMedCrossRefGoogle Scholar
  150. 150.
    Knoers N, Monnens LA (1990) Amiloride-hydrochlorothiazide versus indomethacin-hydrochlorothiazide in the treatment of nephrogenic diabetes insipidus. J Pediatr 117:499–502PubMedCrossRefGoogle Scholar
  151. 151.
    Knoers NV, Deen PM (2001) Molecular and cellular defects in nephrogenic diabetes insipidus. Pediatr Nephrol 16:1146–1152PubMedCrossRefGoogle Scholar
  152. 152.
    Kim GH, Lee JW, Oh YK, Chang HR, Joo KW, Na KY, Earm JH, Knepper MA, Han JS (2004) Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel. J Am Soc Nephrol 15:2836–2843PubMedCrossRefGoogle Scholar
  153. 153.
    Loffing J, Kaissling B (2003) Sodium and calcium transport pathways along the mammalian distal nephron: from rabbit to human. Am J Physiol Renal Physiol 284:F628–F643PubMedGoogle Scholar
  154. 154.
    Los EL, Deen PM, Robben JH (2010) Potential of nonpeptide (ant)agonists to rescue vasopressin V2 receptor mutants for the treatment of X-linked nephrogenic diabetes insipidus. J Neuroendocrinol 22:393–399PubMedCrossRefGoogle Scholar
  155. 155.
    Robben JH, Kortenoeven ML, Sze M, Yae C, Milligan G, Oorschot VM, Klumperman J, Knoers NV, Deen PM (2009) Intracellular activation of vasopressin V2 receptor mutants in nephrogenic diabetes insipidus by nonpeptide agonists. Proc Natl Acad Sci USA 106:12195–12200PubMedCrossRefGoogle Scholar
  156. 156.
    Li JH, Chou CL, Li B, Gavrilova O, Eisner C, Schnermann J, Anderson SA, Deng CX, Knepper MA, Wess J (2009) A selective EP4 PGE2 receptor agonist alleviates disease in a new mouse model of X-linked nephrogenic diabetes insipidus. J Clin Invest 119:3115–3126PubMedCrossRefGoogle Scholar
  157. 157.
    Cohen FE, Kelly JW (2003) Therapeutic approaches to protein-misfolding diseases. Nature 426:905–909PubMedCrossRefGoogle Scholar
  158. 158.
    Eilers M, Schatz G (1986) Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria. Nature 322:228–232PubMedCrossRefGoogle Scholar
  159. 159.
    Morello JP, Salahpour A, Laperriere A, Bernier V, Arthus MF, Lonergan M, Petaja-Repo U, Angers S, Morin D, Bichet DG, Bouvier M (2000) Pharmacological chaperones rescue cell-surface expression and function of misfolded V2 vasopressin receptor mutants. J Clin Invest 105:887–895PubMedCrossRefGoogle Scholar
  160. 160.
    Wuller S, Wiesner B, Loffler A, Furkert J, Krause G, Hermosilla R, Schaefer M, Schulein R, Rosenthal W, Oksche A (2004) Pharmacochaperones post-translationally enhance cell surface expression by increasing conformational stability of wild-type and mutant vasopressin V2 receptors. J Biol Chem 279:47254–47263PubMedCrossRefGoogle Scholar
  161. 161.
    Bernier V, Morello JP, Zarruk A, Debrand N, Salahpour A, Lonergan M, Arthus MF, Laperriere A, Brouard R, Bouvier M, Bichet DG (2006) Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 17:232–243PubMedCrossRefGoogle Scholar
  162. 162.
    Robben JH, Sze M, Knoers NV, Deen PM (2007) Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones: relevance to therapy of nephrogenic diabetes insipidus. Am J Physiol Renal Physiol 292:F253–F260PubMedCrossRefGoogle Scholar
  163. 163.
    Bernier V, Lagace M, Lonergan M, Arthus MF, Bichet DG, Bouvier M (2004) Functional rescue of the constitutively internalized V2 vasopressin receptor mutant R137H by the pharmacological chaperone action of SR49059. Mol Endocrinol 18:2074–2084PubMedCrossRefGoogle Scholar
  164. 164.
    Thibonnier M, Conarty DM, Preston JA, Wilkins PL, Berti-Mattera LN, Mattera R (1998) Molecular pharmacology of human vasopressin receptors. Adv Exp Med Biol 449:251–276PubMedCrossRefGoogle Scholar
  165. 165.
    Jean-Alphonse F, Perkovska S, Frantz MC, Durroux T, Mejean C, Morin D, Loison S, Bonnet D, Hibert M, Mouillac B, Mendre C (2009) Biased agonist pharmacochaperones of the AVP V2 receptor may treat congenital nephrogenic diabetes insipidus. J Am Soc Nephrol 20:2190–2203PubMedCrossRefGoogle Scholar
  166. 166.
    Calebiro D, Nikolaev VO, Persani L, Lohse MJ (2010) Signaling by internalized G-protein-coupled receptors. Trends Pharmacol Sci 31:221–228PubMedCrossRefGoogle Scholar
  167. 167.
    Calebiro D, Nikolaev VO, Lohse MJ (2010) Imaging of persistent cAMP signaling by internalized G protein-coupled receptors. J Mol Endocrinol 45:1–8PubMedCrossRefGoogle Scholar
  168. 168.
    Calebiro D, Nikolaev VO, Gagliani MC, de FT, Dees C, Tacchetti C, Persani L, Lohse MJ (2009) Persistent cAMP-signals triggered by internalized G-protein-coupled receptors. PLoS Biol 7:e1000172Google Scholar
  169. 169.
    Yun J, Schoneberg T, Liu J, Schulz A, Ecelbarger CA, Promeneur D, Nielsen S, Sheng H, Grinberg A, Deng C, Wess J (2000) Generation and phenotype of mice harboring a nonsense mutation in the V2 vasopressin receptor gene. J Clin Invest 106:1361–1371PubMedCrossRefGoogle Scholar
  170. 170.
    Li Y, Shaw S, Kamsteeg EJ, Vandewalle A, Deen PM (2006) Development of lithium-induced nephrogenic diabetes insipidus is dissociated from adenylyl cyclase activity. J Am Soc Nephrol 17:1063–1072PubMedCrossRefGoogle Scholar
  171. 171.
    Olesen ET, Rutzler MR, Moeller HB, Praetorius HA, Fenton RA (2011) Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus. Proc Natl Acad Sci USA 108:12949–12954PubMedCrossRefGoogle Scholar
  172. 172.
    Desai S, April H, Nwaneshiudu C, Ashby B (2000) Comparison of agonist-induced internalization of the human EP2 and EP4 prostaglandin receptors: role of the carboxyl terminus in EP4 receptor sequestration. Mol Pharmacol 58:1279–1286PubMedGoogle Scholar
  173. 173.
    Sugimoto Y, Narumiya S (2007) Prostaglandin E receptors. J Biol Chem 282:11613–11617PubMedCrossRefGoogle Scholar
  174. 174.
    Steinwall M, Akerlund M, Bossmar T, Nishii M, Wright M (2004) ONO-8815Ly, an EP2 agonist that markedly inhibits uterine contractions in women. BJOG 111:120–124PubMedCrossRefGoogle Scholar
  175. 175.
    Yang B, Zhao D, Verkman AS (2009) Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation. FASEB J 23:503–512PubMedCrossRefGoogle Scholar
  176. 176.
    Jiang C, Fang SL, Xiao YF, O'Connor SP, Nadler SG, Lee DW, Jefferson DM, Kaplan JM, Smith AE, Cheng SH (1998) Partial restoration of cAMP-stimulated CFTR chloride channel activity in DeltaF508 cells by deoxyspergualin. Am J Physiol 275:C171–C178PubMedGoogle Scholar
  177. 177.
    Taiyab A, Sreedhar AS, Rao C (2009) Hsp90 inhibitors, GA and 17AAG, lead to ER stress-induced apoptosis in rat histiocytoma. Biochem Pharmacol 78:142–152PubMedCrossRefGoogle Scholar
  178. 178.
    Wang W, Li C, Kwon TH, Knepper MA, Frokiaer J, Nielsen S (2002) AQP3, p-AQP2, and AQP2 expression is reduced in polyuric rats with hypercalcemia: prevention by cAMP-PDE inhibitors. Am J Physiol Renal Physiol 283:F1313–F1325PubMedGoogle Scholar
  179. 179.
    Souness JE, Aldous D, Sargent C (2000) Immunosuppressive and anti-inflammatory effects of cyclic AMP phosphodiesterase (PDE) type 4 inhibitors. Immunopharmacol 47:127–162CrossRefGoogle Scholar

Copyright information

© IPNA 2012

Authors and Affiliations

  • Daniel Wesche
    • 1
  • Peter M. T. Deen
    • 2
  • Nine V. A. M. Knoers
    • 3
  1. 1.Nijmegen Centre for Molecular Life Sciences Graduate SchoolRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  2. 2.Department of Physiology, Nijmegen Centre for Molecular Life SciencesRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.Department of Medical GeneticsUniversity Medical Centre UtrechtUtrechtThe Netherlands

Personalised recommendations