Vasopressin receptor 2

{{Short description|Protein-coding gene in the species Homo sapiens}}

Vasopressin receptor 2 (V2R), or arginine vasopressin receptor 2 (officially called AVPR2), is a protein that acts as receptor for vasopressin.{{cite journal | vauthors = van den Ouweland AM, Knoop MT, Knoers VV, Markslag PW, Rocchi M, Warren ST, Ropers HH, Fahrenholz F, Monnens LA, van Oost BA | title = Colocalization of the gene for nephrogenic diabetes insipidus (DIR) and the vasopressin type 2 receptor gene (AVPR2) in the Xq28 region | journal = Genomics | volume = 13 | issue = 4 | pages = 1350–2 | date = Aug 1992 | pmid = 1324225 | doi = 10.1016/0888-7543(92)90067-3 }} 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 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.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. Stimulation causes the release of von Willebrand factor and factor VIII from the endothelial cells. 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

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

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.{{cite web | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022275s007lbl.pdf | title = SAMSCA (tolvaptan) prescribing information | publisher = US Food and Drug Administration }}

Demeclocycline and lithium carbonate act as indirect antagonists of renal vasopressin V₂ receptors by inhibiting activation of the second messenger cascade of the receptors.{{cite book|author1=Ajay K. Singh|author2=Gordon H. Williams|title=Textbook of Nephro-Endocrinology|url=https://books.google.com/books?id=TsbV_KMn4yAC&pg=PA250|date=12 January 2009|publisher=Academic Press|isbn=978-0-08-092046-7|pages=250–251 }}{{cite book|author1=L. Kovács|author2=B. Lichardus|title=Vasopressin: Disturbed Secretion and Its Effects|url=https://books.google.com/books?id=UQztCAAAQBAJ&pg=PA179|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-009-0449-1|pages=179–180 }}

Pharmacoperones

Vasopressin receptor 2 function has been shown to be deleteriously effected by point mutations in its gene. Some of these mutations, when expressed, cause the receptor to remain in the cytosol. An approach to rescue receptor function utilizes pharmacoperones or molecular chaperones, which are typically small molecules that rescue misfolded proteins to the cell surface. These interact with the receptor to restore cognate receptor function devoid of antagonist or agonist activity. This approach, when effective, should increase therapeutic reach. Pharmacoperones have been identified that restore function of V2R.{{cite journal | vauthors = Janovick JA, Spicer TP, Bannister TD, Smith E, Ganapathy V, Scampavia L | title = Chemical validation and optimization of pharmacoperones targeting vasopressin type 2 receptor mutant | journal = Biochemical Journal | volume = 475 | issue = 18 | pages = 2941–2953 | date = September 2018 | pmid = 30068530 | doi = 10.1042/BCJ20180065 | s2cid = 51894840 }}{{cite journal | vauthors = Janovick JA, Spicer TP, Smith E, Bannister T, Kenakin T, Scampavia L, Conn PM | title = Receptor antagonism/agonism can be uncoupled from pharmacoperone activity | journal = Molecular and Cellular Endocrinology | volume = 434 | pages = 176–185 | date = October 2016 | pmid = 27389877| doi = 10.1016/j.mce.2016.07.003 | pmc = 4983495 }}{{cite journal | vauthors = Smith E, Janovick JA, Bannister T, Shumate J, Scampavia L, Conn PM | title = Identification of Potential Pharmacoperones Capable of Rescuing the Functionality of Misfolded Vasopressin 2 Receptor Involved in Nephrogenic Diabetes Insipidus | journal = SLAS Discovery | volume = 21 | issue = 8 | pages = 824–831 | date = September 2016 | pmid = 27280550 | doi = 10.1177/1087057116653925 | pmc = 5594746 }}{{cite journal | vauthors = Conn PM, Smith E, Hodder P, Janovick JA, Smithson D | title = High-throughput screen for pharmacoperones of the vasopressin type 2 receptor | journal = SLAS Discovery | volume = 18 | issue = 8 | pages = 930–937 | date = September 2013 | pmid = 23640875 | doi = 10.1177/1087057113483559|pmc=3735853 | doi-access = free }}

Interactions

Arginine vasopressin receptor 2 has been shown to interact with C1QTNF1.{{cite journal | vauthors = Innamorati G, Whang MI, Molteni R, Le Gouill C, Birnbaumer M | title = GIP, a G-protein-coupled receptor interacting protein | journal = Regulatory Peptides | volume = 109 | issue = 1–3 | pages = 173–9 | date = Nov 2002 | pmid = 12409230 | doi = 10.1016/S0167-0115(02)00201-X | s2cid = 30853177 }}

References

{{cite journal | vauthors = Birnbaumer M | title = The V2 vasopressin receptor mutations and fluid homeostasis | journal = Cardiovascular Research | volume = 51 | issue = 3 | pages = 409–15 | date = Aug 2001 | pmid = 11476731 | doi = 10.1016/S0008-6363(01)00337-6 | doi-access = free }}
{{cite journal | vauthors = Ishikawa SE | title = [Nephrogenic diabetes insipidus associated with mutations of vasopressin V2 receptors and aquaporin-2] | journal = Nihon Rinsho. Japanese Journal of Clinical Medicine | volume = 60 | issue = 2 | pages = 350–5 | date = Feb 2002 | pmid = 11857925 }}
{{Cite book | vauthors = Thibonnier M, Coles P, Thibonnier A, Shoham M | chapter = Chapter 14 Molecular pharmacology and modeling of vasopressin receptors | title = Vasopressin and Oxytocin: From Genes to Clinical Applications | volume = 139 | pages = 179–96 | year = 2002 | pmid = 12436935 | doi = 10.1016/S0079-6123(02)39016-2 | series = Progress in Brain Research | isbn = 9780444509826 }}
{{cite journal | vauthors = Bichet DG | title = Nephrogenic diabetes insipidus | journal = Advances in Chronic Kidney Disease | volume = 13 | issue = 2 | pages = 96–104 | date = Apr 2006 | pmid = 16580609 | doi = 10.1053/j.ackd.2006.01.006 | url = http://discovery.ucl.ac.uk/1540833/ }}
{{cite journal | vauthors = Robben JH, Knoers NV, Deen PM | title = Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus | journal = American Journal of Physiology. Renal Physiology | volume = 291 | issue = 2 | pages = F257–70 | date = Aug 2006 | pmid = 16825342 | doi = 10.1152/ajprenal.00491.2005 | hdl = 2066/50267 | s2cid = 15392 | url = https://repository.ubn.ru.nl/bitstream/2066/50267/1/50267.pdf | hdl-access = free }}
{{cite journal | vauthors = Pan Y, Metzenberg A, Das S, Jing B, Gitschier J | title = Mutations in the V2 vasopressin receptor gene are associated with X-linked nephrogenic diabetes insipidus | journal = Nature Genetics | volume = 2 | issue = 2 | pages = 103–6 | date = Oct 1992 | pmid = 1303257 | doi = 10.1038/ng1092-103 | s2cid = 26492862 }}
{{cite journal | vauthors = van den Ouweland AM, Dreesen JC, Verdijk M, Knoers NV, Monnens LA, Rocchi M, van Oost BA | title = Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus | journal = Nature Genetics | volume = 2 | issue = 2 | pages = 99–102 | date = Oct 1992 | pmid = 1303271 | doi = 10.1038/ng1092-99 | s2cid = 9281694 }}
{{cite journal | vauthors = van den Ouweland AM, Knoop MT, Knoers VV, Markslag PW, Rocchi M, Warren ST, Ropers HH, Fahrenholz F, Monnens LA, van Oost BA | title = Colocalization of the gene for nephrogenic diabetes insipidus (DIR) and the vasopressin type 2 receptor gene (AVPR2) in the Xq28 region | journal = Genomics | volume = 13 | issue = 4 | pages = 1350–2 | date = Aug 1992 | pmid = 1324225 | doi = 10.1016/0888-7543(92)90067-3 }}
{{cite journal | vauthors = Rosenthal W, Seibold A, Antaramian A, Lonergan M, Arthus MF, Hendy GN, Birnbaumer M, Bichet DG | title = Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus | journal = Nature | volume = 359 | issue = 6392 | pages = 233–5 | date = Sep 1992 | pmid = 1356229 | doi = 10.1038/359233a0 | bibcode = 1992Natur.359..233R | s2cid = 4356664 }}
{{cite journal | vauthors = Seibold A, Brabet P, Rosenthal W, Birnbaumer M | title = Structure and chromosomal localization of the human antidiuretic hormone receptor gene | journal = American Journal of Human Genetics | volume = 51 | issue = 5 | pages = 1078–83 | date = Nov 1992 | pmid = 1415251 | pmc = 1682836 }}
{{cite journal | vauthors = Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, Antaramian A, Brabet P, Rosenthal W | title = Molecular cloning of the receptor for human antidiuretic hormone | journal = Nature | volume = 357 | issue = 6376 | pages = 333–5 | date = May 1992 | pmid = 1534149 | doi = 10.1038/357333a0 | bibcode = 1992Natur.357..333B | s2cid = 4271103 }}
{{cite journal | vauthors = Lolait SJ, O'Carroll AM, McBride OW, Konig M, Morel A, Brownstein MJ | title = Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus | journal = Nature | volume = 357 | issue = 6376 | pages = 336–9 | date = May 1992 | pmid = 1534150 | doi = 10.1038/357336a0 | bibcode = 1992Natur.357..336L | s2cid = 4365214 }}
{{cite journal | vauthors = Knoers N, van der Heyden H, van Oost BA, Monnens L, Willems J, Ropers HH | title = Three-point linkage analysis using multiple DNA polymorphic markers in families with X-linked nephrogenic diabetes insipidus | journal = Genomics | volume = 4 | issue = 3 | pages = 434–7 | date = Apr 1989 | pmid = 2714800 | doi = 10.1016/0888-7543(89)90352-2 }}
{{cite journal | vauthors = Tsukaguchi H, Matsubara H, Taketani S, Mori Y, Seido T, Inada M | title = Binding-, intracellular transport-, and biosynthesis-defective mutants of vasopressin type 2 receptor in patients with X-linked nephrogenic diabetes insipidus | journal = The Journal of Clinical Investigation | volume = 96 | issue = 4 | pages = 2043–50 | date = Oct 1995 | pmid = 7560098 | pmc = 185843 | doi = 10.1172/JCI118252 }}
{{cite journal | vauthors = Faà V, Ventruto ML, Loche S, Bozzola M, Podda R, Cao A, Rosatelli MC | title = Mutations in the vasopressin V2-receptor gene in three families of Italian descent with nephrogenic diabetes insipidus | journal = Human Molecular Genetics | volume = 3 | issue = 9 | pages = 1685–6 | date = Sep 1994 | pmid = 7833930 | doi = 10.1093/hmg/3.9.1685 }}
{{cite journal | vauthors = Birnbaumer M, Gilbert S, Rosenthal W | title = 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 | journal = Molecular Endocrinology | volume = 8 | issue = 7 | pages = 886–94 | date = Jul 1994 | doi = 10.1210/mend.8.7.7984150 | pmid = 7984150 | doi-access = free }}
{{cite journal | vauthors = Wenkert D, Merendino JJ, Shenker A, Thambi N, Robertson GL, Moses AM, Spiegel AM | title = Novel mutations in the V2 vasopressin receptor gene of patients with X-linked nephrogenic diabetes insipidus | journal = Human Molecular Genetics | volume = 3 | issue = 8 | pages = 1429–30 | date = Aug 1994 | pmid = 7987330 | doi = 10.1093/hmg/3.8.1429 }}
{{cite journal | vauthors = Oksche A, Dickson J, Schülein R, Seyberth HW, Müller M, Rascher W, Birnbaumer M, Rosenthal W | title = Two novel mutations in the vasopressin V2 receptor gene in patients with congenital nephrogenic diabetes insipidus | journal = Biochemical and Biophysical Research Communications | volume = 205 | issue = 1 | pages = 552–7 | date = Nov 1994 | pmid = 7999078 | doi = 10.1006/bbrc.1994.2700 }}
{{cite journal | vauthors = Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S | title = Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus | journal = American Journal of Human Genetics | volume = 55 | issue = 2 | pages = 278–86 | date = Aug 1994 | pmid = 8037205 | pmc = 1918376 }}
{{cite journal | vauthors = Yuasa H, Ito M, Oiso Y, Kurokawa M, Watanabe T, Oda Y, Ishizuka T, Tani N, Ito S, Shibata A | title = Novel mutations in the V2 vasopressin receptor gene in two pedigrees with congenital nephrogenic diabetes insipidus | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 79 | issue = 2 | pages = 361–5 | date = Aug 1994 | doi = 10.1210/jcem.79.2.8045948 | pmid = 8045948 }}

External links

[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=ndi GeneReviews/NCBI/NIH/UW entry on Nephrogenic Diabetes Insipidus]
{{cite web | url = https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/897 | title = Symbol Report: AVPR2 | publisher = HUGO Gene Nomenclature Committee (HGNC) }}
{{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2964 | title = Vasopressin and Oxytocin Receptors: V₂ | website = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology }}
{{UCSC gene info|AVPR2}}
{{PDBe-KB2|P30518|Vasopressin V2 receptor}}

Category:G protein-coupled receptors