Vasopressin receptor 2 explained
Vasopressin receptor 2 (V2R), or arginine vasopressin receptor 2 (officially called AVPR2), is a protein that acts as receptor for vasopressin.[1] AVPR2 belongs to the subfamily of G-protein-coupled receptors. Its activity is mediated by the Gs 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.[2] Stimulation causes the release of von Willebrand factor and factor VIII from the endothelial cells.[2] 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.[3]
Demeclocycline and lithium carbonate act as indirect antagonists of renal vasopressin V2 receptors by inhibiting activation of the second messenger cascade of the receptors.[4] [5]
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.[6] [7] [8] [9]
Interactions
Arginine vasopressin receptor 2 has been shown to interact with C1QTNF1.[10]
Further reading
- Birnbaumer M . The V2 vasopressin receptor mutations and fluid homeostasis . Cardiovascular Research . 51 . 3 . 409–15 . Aug 2001 . 11476731 . 10.1016/S0008-6363(01)00337-6 . free .
- Ishikawa SE . [Nephrogenic diabetes insipidus associated with mutations of vasopressin V2 receptors and aquaporin-2] . Nihon Rinsho. Japanese Journal of Clinical Medicine . 60 . 2 . 350–5 . Feb 2002 . 11857925 .
- Book: Thibonnier M, Coles P, Thibonnier A, Shoham M . Chapter 14 Molecular pharmacology and modeling of vasopressin receptors . Vasopressin and Oxytocin: From Genes to Clinical Applications . 139 . 179–96 . 2002 . 12436935 . 10.1016/S0079-6123(02)39016-2 . Progress in Brain Research . 9780444509826 .
- Bichet DG . Nephrogenic diabetes insipidus . Advances in Chronic Kidney Disease . 13 . 2 . 96–104 . Apr 2006 . 16580609 . 10.1053/j.ackd.2006.01.006 .
- Robben JH, Knoers NV, Deen PM . Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus . American Journal of Physiology. Renal Physiology . 291 . 2 . F257–70 . Aug 2006 . 16825342 . 10.1152/ajprenal.00491.2005 . 2066/50267 . 15392 . free .
- Pan Y, Metzenberg A, Das S, Jing B, Gitschier J . Mutations in the V2 vasopressin receptor gene are associated with X-linked nephrogenic diabetes insipidus . Nature Genetics . 2 . 2 . 103–6 . Oct 1992 . 1303257 . 10.1038/ng1092-103 . 26492862 .
- van den Ouweland AM, Dreesen JC, Verdijk M, Knoers NV, Monnens LA, Rocchi M, van Oost BA . Mutations in the vasopressin type 2 receptor gene (AVPR2) associated with nephrogenic diabetes insipidus . Nature Genetics . 2 . 2 . 99–102 . Oct 1992 . 1303271 . 10.1038/ng1092-99 . 9281694 .
- van den Ouweland AM, Knoop MT, Knoers VV, Markslag PW, Rocchi M, Warren ST, Ropers HH, Fahrenholz F, Monnens LA, van Oost BA . 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 . Aug 1992 . 1324225 . 10.1016/0888-7543(92)90067-3 .
- Rosenthal W, Seibold A, Antaramian A, Lonergan M, Arthus MF, Hendy GN, Birnbaumer M, Bichet DG . Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus . Nature . 359 . 6392 . 233–5 . Sep 1992 . 1356229 . 10.1038/359233a0 . 1992Natur.359..233R . 4356664 .
- Seibold A, Brabet P, Rosenthal W, Birnbaumer M . Structure and chromosomal localization of the human antidiuretic hormone receptor gene . American Journal of Human Genetics . 51 . 5 . 1078–83 . Nov 1992 . 1415251 . 1682836 .
- Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, Antaramian A, Brabet P, Rosenthal W . Molecular cloning of the receptor for human antidiuretic hormone . Nature . 357 . 6376 . 333–5 . May 1992 . 1534149 . 10.1038/357333a0 . 1992Natur.357..333B . 4271103 .
- Lolait SJ, O'Carroll AM, McBride OW, Konig M, Morel A, Brownstein MJ . Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus . Nature . 357 . 6376 . 336–9 . May 1992 . 1534150 . 10.1038/357336a0 . 1992Natur.357..336L . 4365214 .
- Knoers N, van der Heyden H, van Oost BA, Monnens L, Willems J, Ropers HH . Three-point linkage analysis using multiple DNA polymorphic markers in families with X-linked nephrogenic diabetes insipidus . Genomics . 4 . 3 . 434–7 . Apr 1989 . 2714800 . 10.1016/0888-7543(89)90352-2 .
- Tsukaguchi H, Matsubara H, Taketani S, Mori Y, Seido T, Inada M . 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 . Oct 1995 . 7560098 . 185843 . 10.1172/JCI118252 .
- Faà V, Ventruto ML, Loche S, Bozzola M, Podda R, Cao A, Rosatelli MC . Mutations in the vasopressin V2-receptor gene in three families of Italian descent with nephrogenic diabetes insipidus . Human Molecular Genetics . 3 . 9 . 1685–6 . Sep 1994 . 7833930 . 10.1093/hmg/3.9.1685 .
- Birnbaumer M, Gilbert S, Rosenthal W . 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 . Jul 1994 . 10.1210/mend.8.7.7984150 . 7984150 . free .
- Wenkert D, Merendino JJ, Shenker A, Thambi N, Robertson GL, Moses AM, Spiegel AM . Novel mutations in the V2 vasopressin receptor gene of patients with X-linked nephrogenic diabetes insipidus . Human Molecular Genetics . 3 . 8 . 1429–30 . Aug 1994 . 7987330 . 10.1093/hmg/3.8.1429 .
- Oksche A, Dickson J, Schülein R, Seyberth HW, Müller M, Rascher W, Birnbaumer M, Rosenthal W . 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 . Nov 1994 . 7999078 . 10.1006/bbrc.1994.2700 .
- Bichet DG, Birnbaumer M, Lonergan M, Arthus MF, Rosenthal W, Goodyer P, Nivet H, Benoit S, Giampietro P, Simonetti S . Nature and recurrence of AVPR2 mutations in X-linked nephrogenic diabetes insipidus . American Journal of Human Genetics . 55 . 2 . 278–86 . Aug 1994 . 8037205 . 1918376 .
- Yuasa H, Ito M, Oiso Y, Kurokawa M, Watanabe T, Oda Y, Ishizuka T, Tani N, Ito S, Shibata A . 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 . Aug 1994 . 10.1210/jcem.79.2.8045948 . 8045948 .
External links
Notes and References
- van den Ouweland AM, Knoop MT, Knoers VV, Markslag PW, Rocchi M, Warren ST, Ropers HH, Fahrenholz F, Monnens LA, van Oost BA . 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 . Aug 1992 . 1324225 . 10.1016/0888-7543(92)90067-3 .
- 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.
- Web site: SAMSCA (tolvaptan) prescribing information . US Food and Drug Administration .
- Book: Ajay K. Singh. Gordon H. Williams. Textbook of Nephro-Endocrinology. 12 January 2009. Academic Press. 978-0-08-092046-7. 250–251 .
- Book: L. Kovács. B. Lichardus. Vasopressin: Disturbed Secretion and Its Effects. 6 December 2012. Springer Science & Business Media. 978-94-009-0449-1. 179–180 .
- Janovick JA, Spicer TP, Bannister TD, Smith E, Ganapathy V, Scampavia L . Chemical validation and optimization of pharmacoperones targeting vasopressin type 2 receptor mutant . Biochemical Journal . 475 . 18 . 2941–2953 . September 2018 . 30068530 . 10.1042/BCJ20180065 . 51894840 .
- Janovick JA, Spicer TP, Smith E, Bannister T, Kenakin T, Scampavia L, Conn PM . Receptor antagonism/agonism can be uncoupled from pharmacoperone activity . Molecular and Cellular Endocrinology . 434 . 176–185 . October 2016 . 27389877. 10.1016/j.mce.2016.07.003 . 4983495 .
- Smith E, Janovick JA, Bannister T, Shumate J, Scampavia L, Conn PM . Identification of Potential Pharmacoperones Capable of Rescuing the Functionality of Misfolded Vasopressin 2 Receptor Involved in Nephrogenic Diabetes Insipidus . SLAS Discovery . 21 . 8 . 824–831 . September 2016 . 27280550 . 10.1177/1087057116653925 . 5594746 .
- Conn PM, Smith E, Hodder P, Janovick JA, Smithson D . High-throughput screen for pharmacoperones of the vasopressin type 2 receptor . SLAS Discovery . 18 . 8 . 930–937 . September 2013 . 23640875 . 10.1177/1087057113483559. 3735853 . free .
- Innamorati G, Whang MI, Molteni R, Le Gouill C, Birnbaumer M . GIP, a G-protein-coupled receptor interacting protein . Regulatory Peptides . 109 . 1–3 . 173–9 . Nov 2002 . 12409230 . 10.1016/S0167-0115(02)00201-X . 30853177 .