AVPR2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesAVPR2, ADHR, DI1, DIR, DIR3, NDI, V2R, arginine vasopressin receptor 2, NDI1
External IDsOMIM: 300538 MGI: 88123 HomoloGene: 20064 GeneCards: AVPR2
Orthologs
SpeciesHumanMouse
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 MbChr X: 72.94 – 72.94 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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 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.[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:

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]

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.[10][11][12][13]

Interactions

Arginine vasopressin receptor 2 has been shown to interact with C1QTNF1.[14]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000126895 - Ensembl, May 2017
  2. ^ a b c 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. ^ a b 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. ^ Janovick JA, Spicer TP, Bannister TD, Smith E, Ganapathy V, Scampavia L (September 2018). "Chemical validation and optimization of pharmacoperones targeting vasopressin type 2 receptor mutant". Biochemical Journal. 475 (18): 2941–2953. doi:10.1042/BCJ20180065. PMID 30068530. S2CID 51894840.
  11. ^ Janovick JA, Spicer TP, Smith E, Bannister T, Kenakin T, Scampavia L, Conn PM (October 2016). "Receptor antagonism/agonism can be uncoupled from pharmacoperone activity". Molecular and Cellular Endocrinology. 434: 176–185. doi:10.1016/j.mce.2016.07.003. PMC 4983495. PMID 27389877.
  12. ^ Smith E, Janovick JA, Bannister T, Shumate J, Scampavia L, Conn PM (September 2016). "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. doi:10.1177/1087057116653925. PMC 5594746. PMID 27280550.
  13. ^ Conn PM, Smith E, Hodder P, Janovick JA, Smithson D (September 2013). "High-throughput screen for pharmacoperones of the vasopressin type 2 receptor". SLAS Discovery. 18 (8): 930–937. doi:10.1177/1087057113483559. PMC 3735853. PMID 23640875.
  14. ^ 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. S2CID 30853177.

Further reading

External links

Cell surface receptor: G protein-coupled receptors
Neuropeptide receptors
Oxytocin and vasopressin receptor modulators
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