{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAVPR2, the type‐2 vasopressin receptor, is a prototypical G protein–coupled receptor whose activation by antidiuretic hormone (AVP) plays a central role in water homeostasis. Upon ligand binding, the receptor undergoes conformational changes that promote Gs‐protein activation and subsequent cyclic AMP (cAMP) production, leading to the trafficking of aquaporin‐2 water channels to the apical membrane of renal collecting duct cells. Detailed structural studies using phosphopeptides derived from the receptor’s carboxy‐terminal tail have revealed how receptor phosphorylation directs β‐arrestin recruitment and modulates both classical and noncanonical signaling cascades."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in the AVPR2 gene underscore its pivotal role in fluid balance and have been implicated in divergent water balance disorders. Inactivating mutations typically cause nephrogenic diabetes insipidus (NDI) by impairing receptor signaling and trafficking, while certain activating mutations lead to the nephrogenic syndrome of inappropriate antidiuresis (NSIAD), marked by constitutive receptor activity and prolonged cAMP production. Clinical and genetic studies reveal that these mutations, which affect key residues involved in G protein coupling, arrestin recruitment, and receptor internalization, not only impair the renal response to AVP but also display variable inheritance patterns and phenotypes. These findings have been corroborated by detailed genotype–phenotype analyses and molecular investigations demonstrating altered receptor internalization, ubiquitination, and interactions with accessory proteins, as well as by studies mapping receptor messenger RNA expression in diverse nephron segments."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical signaling, AVPR2 function is intricately regulated by processes that control its cellular trafficking, post‐translational modifications, and interactions with accessory proteins. Pharmacological chaperones and small molecules capable of rescuing misfolded or mistrafficked mutant receptors have been identified, underscoring the therapeutic potential for correcting receptor defects. Moreover, regulatory proteins such as β‐arrestins and ubiquitin‐related adaptors modulate receptor internalization and degradation, while studies employing receptor mimetic peptides have shed light on the structural determinants necessary for Gs protein activation and receptor dimerization. These mechanistic insights not only inform on renal water reabsorption but also extend to extra‐renal roles in conditions such as polycystic kidney disease, Meniere’s disease, and even certain cancers, where V2R signaling modulates cellular proliferation and fluid balance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "50"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Arun K Shukla, Aashish Manglik, Andrew C Kruse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure of active β-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature12120"}], "href": "https://doi.org/10.1038/nature12120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23604254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23604254"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Timothy N Feinstein, Naofumi Yui, Matthew J Webber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Noncanonical control of vasopressin receptor type 2 signaling by retromer and arrestin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.445098"}], "href": "https://doi.org/10.1074/jbc.M112.445098"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23935101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23935101"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Joris H Robben, Nine V A M Knoers, Peter M T Deen "}, {"type": "b", "children": [{"type": "t", "text": "Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00491.2005"}], "href": "https://doi.org/10.1152/ajprenal.00491.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16825342"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16825342"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sonia Terrillon, Claude Barberis, Michel Bouvier "}, {"type": "b", "children": [{"type": "t", "text": "Heterodimerization of V1a and V2 vasopressin receptors determines the interaction with beta-arrestin and their trafficking patterns."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0305322101"}], "href": "https://doi.org/10.1073/pnas.0305322101"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14757828"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14757828"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "K Mutig, A Paliege, T Kahl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vasopressin V2 receptor expression along rat, mouse, and human renal epithelia with focus on TAL."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00196.2007"}], "href": "https://doi.org/10.1152/ajprenal.00196.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17626156"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17626156"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Stefan Wüller, Burkhard Wiesner, Anja Löffler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacochaperones post-translationally enhance cell surface expression by increasing conformational stability of wild-type and mutant vasopressin V2 receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M408154200"}], "href": "https://doi.org/10.1074/jbc.M408154200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15319430"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15319430"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Negin P Martin, Robert J Lefkowitz, Sudha K Shenoy "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of V2 vasopressin receptor degradation by agonist-promoted ubiquitination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M308285200"}], "href": "https://doi.org/10.1074/jbc.M308285200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12960162"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12960162"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Elias Spanakis, Edrice Milord, Claudia Gragnoli "}, {"type": "b", "children": [{"type": "t", "text": "AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.21552"}], "href": "https://doi.org/10.1002/jcp.21552"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18726898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18726898"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Pascale G Charest, Michel Bouvier "}, {"type": "b", "children": [{"type": "t", "text": "Palmitoylation of the V2 vasopressin receptor carboxyl tail enhances beta-arrestin recruitment leading to efficient receptor endocytosis and ERK1/2 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M306589200"}], "href": "https://doi.org/10.1074/jbc.M306589200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12900404"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12900404"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Anja Thielen, Morad Oueslati, Ricardo Hermosilla, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The hydrophobic amino acid residues in the membrane-proximal C tail of the G protein-coupled vasopressin V2 receptor are necessary for transport-competent receptor folding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2005.08.043"}], "href": "https://doi.org/10.1016/j.febslet.2005.08.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16162341"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16162341"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Qing-Tao He, Peng Xiao, Shen-Ming Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural studies of phosphorylation-dependent interactions between the V2R receptor and arrestin-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-22731-x"}], "href": "https://doi.org/10.1038/s41467-021-22731-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33888704"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33888704"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Guy Decaux, Frédéric Vandergheynst, Yasmina Bouko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nephrogenic syndrome of inappropriate antidiuresis in adults: high phenotypic variability in men and women from a large pedigree."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2006090987"}], "href": "https://doi.org/10.1681/ASN.2006090987"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17229917"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17229917"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Daniel G Bichet "}, {"type": "b", "children": [{"type": "t", "text": "Nephrogenic diabetes insipidus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Chronic Kidney Dis (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.ackd.2006.01.006"}], "href": "https://doi.org/10.1053/j.ackd.2006.01.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16580609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16580609"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "T Kitahara, K Doi, C Maekawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Meniere's attacks occur in the inner ear with excessive vasopressin type-2 receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuroendocrinol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2826.2008.01792.x"}], "href": "https://doi.org/10.1111/j.1365-2826.2008.01792.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19094077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19094077"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Daniel G Bichet, Detlef Bockenhauer "}, {"type": "b", "children": [{"type": "t", "text": "Genetic forms of nephrogenic diabetes insipidus (NDI): Vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Best Pract Res Clin Endocrinol Metab (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.beem.2016.02.010"}], "href": "https://doi.org/10.1016/j.beem.2016.02.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27156763"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27156763"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Moulay D Rochdi, Gabriel A Vargas, Eric Carpentier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterization of vasopressin type 2 receptor substitutions (R137H/C/L) leading to nephrogenic diabetes insipidus and nephrogenic syndrome of inappropriate antidiuresis: implications for treatments."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharmacol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1124/mol.109.061804"}], "href": "https://doi.org/10.1124/mol.109.061804"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20159941"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20159941"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Sei Sasaki, Motoko Chiga, Eriko Kikuchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Nephrol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10157-012-0726-z"}], "href": "https://doi.org/10.1007/s10157-012-0726-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23150186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23150186"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Richard Bouley, Gayle Hawthorn, Leileata M Russo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aquaporin 2 (AQP2) and vasopressin type 2 receptor (V2R) endocytosis in kidney epithelial cells: AQP2 is located in 'endocytosis-resistant' membrane domains after vasopressin treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BC20040054"}], "href": "https://doi.org/10.1042/BC20040054"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16563128"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16563128"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Martina Kocan, Heng B See, Natália G Sampaio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Agonist-independent interactions between beta-arrestins and mutant vasopressin type II receptors associated with nephrogenic syndrome of inappropriate antidiuresis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2008-0321"}], "href": "https://doi.org/10.1210/me.2008-0321"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19179480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19179480"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "D Bockenhauer, D G Bichet "}, {"type": "b", "children": [{"type": "t", "text": "Inherited secondary nephrogenic diabetes insipidus: concentrating on humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Renal Physiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajprenal.00639.2012"}], "href": "https://doi.org/10.1152/ajprenal.00639.2012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23364801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23364801"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "László S Erdélyi, W Alexander Mann, Deborah J Morris-Rosendahl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation in the V2 vasopressin receptor gene, AVPR2, causes nephrogenic syndrome of inappropriate diuresis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ki.2015.181"}], "href": "https://doi.org/10.1038/ki.2015.181"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26131744"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26131744"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Detlef Bockenhauer, Eric Carpentier, Driss Rochdi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vasopressin type 2 receptor V88M mutation: molecular basis of partial and complete nephrogenic diabetes insipidus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nephron Physiol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000245059"}], "href": "https://doi.org/10.1159/000245059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19816050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19816050"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Masashi Demura, Yoshiyu Takeda, Takashi Yoneda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two novel types of contiguous gene deletion of the AVPR2 and ARHGAP4 genes in unrelated Japanese kindreds with nephrogenic diabetes insipidus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.10011"}], "href": "https://doi.org/10.1002/humu.10011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11754100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11754100"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Alexander Oksche, Gabriele Leder, Susanne Valet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Variant amino acids in the extracellular loops of murine and human vasopressin V2 receptors account for differences in cell surface expression and ligand affinity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/mend.16.4.0796"}], "href": "https://doi.org/10.1210/mend.16.4.0796"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11923476"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11923476"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Kazuhiro Takahashi, Noriko Makita, Katsunori Manaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "V2 vasopressin receptor (V2R) mutations in partial nephrogenic diabetes insipidus highlight protean agonism of V2R antagonists."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.268797"}], "href": "https://doi.org/10.1074/jbc.M111.268797"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22144672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22144672"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Mia Faerch, Jane H Christensen, Thomas J Corydon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Partial nephrogenic diabetes insipidus caused by a novel mutation in the AVPR2 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Endocrinol (Oxf) (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2265.2007.03054.x"}], "href": "https://doi.org/10.1111/j.1365-2265.2007.03054.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17941907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17941907"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Mari Satoh, Sayaka Ogikubo, Atsuko Yoshizawa-Ogasawara "}, {"type": "b", "children": [{"type": "t", "text": "Correlation between clinical phenotypes and X-inactivation patterns in six female carriers with heterozygote vasopressin type 2 receptor gene mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr J (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1507/endocrj.k07-083"}], "href": "https://doi.org/10.1507/endocrj.k07-083"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18323675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18323675"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Chao Gao, Paul J Higgins, Wenzheng Zhang "}, {"type": "b", "children": [{"type": "t", "text": "AQP2: Mutations Associated with Congenital Nephrogenic Diabetes Insipidus and Regulation by Post-Translational Modifications and Protein-Protein Interactions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells9102172"}], "href": "https://doi.org/10.3390/cells9102172"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32993088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32993088"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Sayali A Ranadive, Baran Ersoy, Helene Favre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification, characterization and rescue of a novel vasopressin-2 receptor mutation causing nephrogenic diabetes insipidus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Endocrinol (Oxf) (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2265.2008.03513.x"}], "href": "https://doi.org/10.1111/j.1365-2265.2008.03513.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19170711"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19170711"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Chia-Hsiang Chen, Wen-Yu Chen, Hui-Lin Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of mutations in the arginine vasopressin receptor 2 gene causing nephrogenic diabetes insipidus in Chinese patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s100380200002"}], "href": "https://doi.org/10.1007/s100380200002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11916004"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11916004"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Vassos Neocleous, Nicos Skordis, Christos Shammas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of a novel X-linked AVPR2 mutation causing partial nephrogenic diabetes insipidus: a case report and review of the literature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metabolism (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.metabol.2012.01.005"}], "href": "https://doi.org/10.1016/j.metabol.2012.01.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22386940"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22386940"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Pamela Carroll, Hamad Al-Mojalli, Abbas Al-Abbad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutations underlying nephrogenic diabetes insipidus in Arab families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Med (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/01.gim.0000223554.46981.7a"}], "href": "https://doi.org/10.1097/01.gim.0000223554.46981.7a"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16845277"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16845277"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Serena Milano, Monica Carmosino, Andrea Gerbino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hereditary Nephrogenic Diabetes Insipidus: Pathophysiology and Possible Treatment. An Update."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms18112385"}], "href": "https://doi.org/10.3390/ijms18112385"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29125546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29125546"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "J H Robben, M Sze, N V A M Knoers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rescue of vasopressin V2 receptor mutants by chemical chaperones: specificity and mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e05-06-0579"}], "href": "https://doi.org/10.1091/mbc.e05-06-0579"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16267275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16267275"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Elsa-Noah N'Diaye, Aylin C Hanyaloglu, Kimberly K Kajihara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitin-like protein PLIC-2 is a negative regulator of G protein-coupled receptor endocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e07-08-0775"}], "href": "https://doi.org/10.1091/mbc.e07-08-0775"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18199683"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18199683"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Markus M Rinschen, Bernhard Schermer, Thomas Benzing "}, {"type": "b", "children": [{"type": "t", "text": "Vasopressin-2 receptor signaling and autosomal dominant polycystic kidney disease: from bench to bedside and back again."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2013101037"}], "href": "https://doi.org/10.1681/ASN.2013101037"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24556353"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24556353"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Anatoly Tiulpakov, Carl W White, Rekhati S Abhayawardana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations of Vasopressin Receptor 2 Including Novel L312S Have Differential Effects on Trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2016-1002"}], "href": "https://doi.org/10.1210/me.2016-1002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27355191"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27355191"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Hilary Highfield Nickols, Vikas N Shah, Walter J Chazin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Calmodulin interacts with the V2 vasopressin receptor: elimination of binding to the C terminus also eliminates arginine vasopressin-stimulated elevation of intracellular calcium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M407351200"}], "href": "https://doi.org/10.1074/jbc.M407351200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15319442"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15319442"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "A H Molnár, C Varga, A Berkó, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibitory effect of vasopressin receptor antagonist OPC-31260 on experimental brain oedema induced by global cerebral ischaemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neurochir (Wien) (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00701-007-1400-1"}], "href": "https://doi.org/10.1007/s00701-007-1400-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18288441"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18288441"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Stephen P Armstrong, Ruth M Seeber, Mohammed Akli Ayoub, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of three vasopressin receptor 2 variants: an apparent polymorphism (V266A) and two loss-of-function mutations (R181C and M311V)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0065885"}], "href": "https://doi.org/10.1371/journal.pone.0065885"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23762448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23762448"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Sébastien Granier, Sonia Terrillon, Robert Pascal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A cyclic peptide mimicking the third intracellular loop of the V2 vasopressin receptor inhibits signaling through its interaction with receptor dimer and G protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M405089200"}], "href": "https://doi.org/10.1074/jbc.M405089200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15452133"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15452133"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Tadashi Kitahara, Chie Maekawa, Kaoru Kizawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma vasopressin and V2 receptor in the endolymphatic sac in patients with delayed endolymphatic hydrops."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Otol Neurotol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MAO.0b013e3181b11db5"}], "href": "https://doi.org/10.1097/MAO.0b013e3181b11db5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19638944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19638944"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Nidhi Dwivedi, Shixin Tao, Abeda Jamadar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Epithelial Vasopressin Type-2 Receptors Regulate Myofibroblasts by a YAP-CCN2-Dependent Mechanism in Polycystic Kidney Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Am Soc Nephrol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1681/ASN.2020020190"}], "href": "https://doi.org/10.1681/ASN.2020020190"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32554753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32554753"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "S Gupta, T D Cheetham, H J Lambert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Thirst perception and arginine vasopressin production in a kindred with an activating mutation of the type 2 vasopressin receptor: the pathophysiology of nephrogenic syndrome of inappropriate antidiuresis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Endocrinol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/EJE-09-0246"}], "href": "https://doi.org/10.1530/EJE-09-0246"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19542240"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19542240"}]}, {"type": "r", "ref": 45, "children": [{"type": "t", "text": "Lingli Huang, Gemma Poke, Jozef Gecz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel contiguous gene deletion of AVPR2 and ARHGAP4 genes in male dizygotic twins with nephrogenic diabetes insipidus and intellectual disability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.35591"}], "href": "https://doi.org/10.1002/ajmg.a.35591"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22965914"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22965914"}]}, {"type": "r", "ref": 46, "children": [{"type": "t", "text": "Steven Soule, Chris Florkowski, Howard Potter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Intermittent severe, symptomatic hyponatraemia due to the nephrogenic syndrome of inappropriate antidiuresis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Clin Biochem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1258/acb.2007.007211"}], "href": "https://doi.org/10.1258/acb.2007.007211"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18753429"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18753429"}]}, {"type": "r", "ref": 47, "children": [{"type": "t", "text": "Davide Bolignano, Maria Antonietta Medici, Giuseppe Coppolino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aquaretic inhibits renal cancer proliferation: Role of vasopressin receptor-2 (V2-R)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Urol Oncol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.urolonc.2008.12.014"}], "href": "https://doi.org/10.1016/j.urolonc.2008.12.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19217806"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19217806"}]}, {"type": "r", "ref": 48, "children": [{"type": "t", "text": "Tamara Hew-Butler, Jed Hummel, Brian C Rider, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the effects of the vasopressin V2 receptor on sweating, fluid balance, and performance during exercise."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Regul Integr Comp Physiol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpregu.00120.2014"}], "href": "https://doi.org/10.1152/ajpregu.00120.2014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24944242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24944242"}]}, {"type": "r", "ref": 49, "children": [{"type": "t", "text": "László Sándor Erdélyi, András Balla, Attila Patócs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered agonist sensitivity of a mutant v2 receptor suggests a novel therapeutic strategy for nephrogenic diabetes insipidus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2013-1424"}], "href": "https://doi.org/10.1210/me.2013-1424"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24628417"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24628417"}]}, {"type": "r", "ref": 50, "children": [{"type": "t", "text": "E Kojro, R Postina, S Gilbert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural requirements for V2 vasopressin receptor proteolytic cleavage."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Biochem (1999)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1432-1327.1999.00892.x"}], "href": "https://doi.org/10.1046/j.1432-1327.1999.00892.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10561596"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10561596"}]}]}]}