Vasopressin receptor 2

Vasopressin receptor 2 (V2R), or arginine vasopressin receptor 2 (officially called AVPR2), is a protein that acts as receptor for vasopressin.[5] AVPR2 belongs to the subfamily of G-protein-coupled receptors. Its activity is mediated by the G_s type of G proteins, which stimulate adenylate cyclase.

AVPR2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4JQI
Identifiers
Aliases	AVPR2, ADHR, DI1, DIR, DIR3, NDI, V2R, arginine vasopressin receptor 2
External IDs	OMIM: 300538 MGI: 88123 HomoloGene: 20064 GeneCards: AVPR2
Gene location (Human) Chr. X chromosome (human)[1] Band Xq28 Start 153,902,531 bp[1] End 153,907,166 bp[1]
Gene location (Mouse) Chr. X chromosome (mouse)[2] Band X A7.3|X 37.46 cM Start 73,892,102 bp[2] End 73,895,502 bp[2]
Gene ontology Molecular function • G-protein coupled receptor activity • peptide binding • signal transducer activity • GO:0001948 protein binding • vasopressin receptor activity Cellular component • integral component of membrane • endosome • Golgi apparatus • membrane • cell membrane • integral component of plasma membrane • endoplasmic reticulum • clathrin-coated vesicle membrane Biological process • hemostasis • excretion • adenylate cyclase-modulating G-protein coupled receptor signaling pathway • regulation of systemic arterial blood pressure by vasopressin • activation of adenylate cyclase activity • response to peptide • cellular response to hormone stimulus • positive regulation of vasoconstriction • renal water homeostasis • positive regulation of protein ubiquitination • signal transduction • membrane organization • G-protein coupled receptor signaling pathway • positive regulation of gene expression • positive regulation of systemic arterial blood pressure • I-kappaB kinase/NF-kappaB signaling • positive regulation of cell proliferation • telencephalon development • interferon-gamma production • response to cytokine • negative regulation of urine volume • negative regulation of renal sodium excretion • positive regulation of blood pressure Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	554	12000
Ensembl	ENSG00000126895	ENSMUSG00000031390
UniProt	P30518	O88721
RefSeq (mRNA)	NM_000054 NM_001146151	NM_001276298 NM_001276299 NM_019404
RefSeq (protein)	NP_000045 NP_001139623	NP_001263227 NP_001263228 NP_062277
Location (UCSC)	Chr X: 153.9 – 153.91 Mb	Chr X: 73.89 – 73.9 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

AVPR2 is expressed in the kidney tubule, predominantly in the membrane of cells of the distal convoluted tubule and collecting ducts, in fetal lung tissue and lung cancer, the last two being associated with alternative splicing. AVPR2 is also expressed outside the kidney in vascular endothelium.[6] Stimulation causes the release of von Willebrand factor and factor VIII from the endothelial cells.[6] Because von Willebrand factor helps stabilize circulating levels of factor VIII, the vasopressin analog desmopressin can be used to stimulate the AVPR2 receptor and increase levels of circulating factor VIII. This is useful in the treatment of hemophilia A as well as Von Willebrand disease.

In the kidney, AVPR2's primary property is to respond to arginine vasopressin by stimulating mechanisms that concentrate the urine and maintain water homeostasis in the organism. When the function of AVPR2 is lost, the disease nephrogenic diabetes insipidus (NDI) results.

Antagonists

Further information: Vasopressin receptor antagonist

Vasopressin receptor antagonists that are selective for the V2 receptor include:

• Tolvaptan (FDA-approved)
• Lixivaptan
• Mozavaptan
• Satavaptan

Their main uses are in hyponatremia, such as that caused by syndrome of inappropriate antidiuretic hormone (SIADH) and heart failure, however these agents should be avoided in patients with cirrhosis.[7]

Demeclocycline and lithium carbonate act as indirect antagonists of renal vasopressin V₂ receptors by inhibiting activation of the second messenger cascade of the receptors.[8][9]

Interactions

Arginine vasopressin receptor 2 has been shown to interact with C1QTNF1.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000126895 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031390 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. van den Ouweland AM, Knoop MT, Knoers VV, Markslag PW, Rocchi M, Warren ST, Ropers HH, Fahrenholz F, Monnens LA, van Oost BA (Aug 1992). "Colocalization of the gene for nephrogenic diabetes insipidus (DIR) and the vasopressin type 2 receptor gene (AVPR2) in the Xq28 region". Genomics. 13 (4): 1350–2. doi:10.1016/0888-7543(92)90067-3. PMID 1324225.
6. Jackson EK (2018). "Drugs Affecting Renal Excretory Function". In: Brunton LL, Hilal-Dandan R, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e New York, NY: McGraw-Hill.
7. "SAMSCA (tolvaptan) prescribing information" (PDF). US Food and Drug Administration.
8. Ajay K. Singh, Gordon H. Williams (12 January 2009). Textbook of Nephro-Endocrinology. Academic Press. pp. 250–251. ISBN 978-0-08-092046-7.
9. L. Kovács, B. Lichardus (6 December 2012). Vasopressin: Disturbed Secretion and Its Effects. Springer Science & Business Media. pp. 179–180. ISBN 978-94-009-0449-1.
10. Innamorati G, Whang MI, Molteni R, Le Gouill C, Birnbaumer M (Nov 2002). "GIP, a G-protein-coupled receptor interacting protein". Regulatory Peptides. 109 (1–3): 173–9. doi:10.1016/S0167-0115(02)00201-X. PMID 12409230.

Further reading

• Birnbaumer M (Aug 2001). "The V2 vasopressin receptor mutations and fluid homeostasis". Cardiovascular Research. 51 (3): 409–15. doi:10.1016/S0008-6363(01)00337-6. PMID 11476731.
• Ishikawa SE (Feb 2002). "[Nephrogenic diabetes insipidus associated with mutations of vasopressin V2 receptors and aquaporin-2]". Nihon Rinsho. Japanese Journal of Clinical Medicine. 60 (2): 350–5. PMID 11857925.
• Thibonnier M, Coles P, Thibonnier A, Shoham M (2002). Molecular pharmacology and modeling of vasopressin receptors. Progress in Brain Research. 139. pp. 179–96. doi:10.1016/S0079-6123(02)39016-2. ISBN 9780444509826. PMID 12436935.
• Bichet DG (Apr 2006). "Nephrogenic diabetes insipidus". Advances in Chronic Kidney Disease. 13 (2): 96–104. doi:10.1053/j.ackd.2006.01.006. PMID 16580609.
• Robben JH, Knoers NV, Deen PM (Aug 2006). "Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus" (PDF). American Journal of Physiology. Renal Physiology. 291 (2): F257–70. doi:10.1152/ajprenal.00491.2005. hdl:2066/50267. PMID 16825342.
• Pan Y, Metzenberg A, Das S, Jing B, Gitschier J (Oct 1992). "Mutations in the V2 vasopressin receptor gene are associated with X-linked nephrogenic diabetes insipidus". Nature Genetics. 2 (2): 103–6. doi:10.1038/ng1092-103. PMID 1303257.
• van den Ouweland AM, Dreesen JC, Verdijk M, Knoers NV, Monnens LA, Rocchi M, van Oost BA (Oct 1992). "Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus". Nature Genetics. 2 (2): 99–102. doi:10.1038/ng1092-99. PMID 1303271.
• van den Ouweland AM, Knoop MT, Knoers VV, Markslag PW, Rocchi M, Warren ST, Ropers HH, Fahrenholz F, Monnens LA, van Oost BA (Aug 1992). "Colocalization of the gene for nephrogenic diabetes insipidus (DIR) and the vasopressin type 2 receptor gene (AVPR2) in the Xq28 region". Genomics. 13 (4): 1350–2. doi:10.1016/0888-7543(92)90067-3. PMID 1324225.
• Rosenthal W, Seibold A, Antaramian A, Lonergan M, Arthus MF, Hendy GN, Birnbaumer M, Bichet DG (Sep 1992). "Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus". Nature. 359 (6392): 233–5. doi:10.1038/359233a0. PMID 1356229.
• Seibold A, Brabet P, Rosenthal W, Birnbaumer M (Nov 1992). "Structure and chromosomal localization of the human antidiuretic hormone receptor gene". American Journal of Human Genetics. 51 (5): 1078–83. PMC 1682836. PMID 1415251.
• Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, Antaramian A, Brabet P, Rosenthal W (May 1992). "Molecular cloning of the receptor for human antidiuretic hormone". Nature. 357 (6376): 333–5. doi:10.1038/357333a0. PMID 1534149.
• Lolait SJ, O'Carroll AM, McBride OW, Konig M, Morel A, Brownstein MJ (May 1992). "Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus". Nature. 357 (6376): 336–9. doi:10.1038/357336a0. PMID 1534150.
• Knoers N, van der Heyden H, van Oost BA, Monnens L, Willems J, Ropers HH (Apr 1989). "Three-point linkage analysis using multiple DNA polymorphic markers in families with X-linked nephrogenic diabetes insipidus". Genomics. 4 (3): 434–7. doi:10.1016/0888-7543(89)90352-2. PMID 2714800.
• Tsukaguchi H, Matsubara H, Taketani S, Mori Y, Seido T, Inada M (Oct 1995). "Binding-, intracellular transport-, and biosynthesis-defective mutants of vasopressin type 2 receptor in patients with X-linked nephrogenic diabetes insipidus". The Journal of Clinical Investigation. 96 (4): 2043–50. doi:10.1172/JCI118252. PMC 185843. PMID 7560098.
• Faà V, Ventruto ML, Loche S, Bozzola M, Podda R, Cao A, Rosatelli MC (Sep 1994). "Mutations in the vasopressin V2-receptor gene in three families of Italian descent with nephrogenic diabetes insipidus". Human Molecular Genetics. 3 (9): 1685–6. doi:10.1093/hmg/3.9.1685. PMID 7833930.
• Birnbaumer M, Gilbert S, Rosenthal W (Jul 1994). "An extracellular congenital nephrogenic diabetes insipidus mutation of the vasopressin receptor reduces cell surface expression, affinity for ligand, and coupling to the Gs/adenylyl cyclase system". Molecular Endocrinology. 8 (7): 886–94. doi:10.1210/me.8.7.886. PMID 7984150.
• Wenkert D, Merendino JJ, Shenker A, Thambi N, Robertson GL, Moses AM, Spiegel AM (Aug 1994). "Novel mutations in the V2 vasopressin receptor gene of patients with X-linked nephrogenic diabetes insipidus". Human Molecular Genetics. 3 (8): 1429–30. doi:10.1093/hmg/3.8.1429. PMID 7987330.
• Oksche A, Dickson J, Schülein R, Seyberth HW, Müller M, Rascher W, Birnbaumer M, Rosenthal W (Nov 1994). "Two novel mutations in the vasopressin V2 receptor gene in patients with congenital nephrogenic diabetes insipidus". Biochemical and Biophysical Research Communications. 205 (1): 552–7. doi:10.1006/bbrc.1994.2700. PMID 7999078.
• Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S (Aug 1994). "Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus". American Journal of Human Genetics. 55 (2): 278–86. PMC 1918376. PMID 8037205.
• Yuasa H, Ito M, Oiso Y, Kurokawa M, Watanabe T, Oda Y, Ishizuka T, Tani N, Ito S, Shibata A (Aug 1994). "Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus". The Journal of Clinical Endocrinology and Metabolism. 79 (2): 361–5. doi:10.1210/jc.79.2.361. PMID 8045948.

External links

• GeneReviews/NCBI/NIH/UW entry on Nephrogenic Diabetes Insipidus
• "Symbol Report: AVPR2". HUGO Gene Nomenclature Committee (HGNC).
• "Vasopressin and Oxytocin Receptors: V₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
• Human AVPR2 genome location and AVPR2 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: P30518 (Vasopressin V2 receptor) at the PDBe-KB.