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, NDI1
External IDs	OMIM: 300538; MGI: 88123; HomoloGene: 20064; GeneCards: AVPR2; OMA:AVPR2 - orthologs
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 72,935,708 bp[2] End 72,939,108 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart subcutaneous adipose tissue left ventricle granulocyte vena cava human kidney muscle of thigh left uterine tube gastrocnemius muscle right auricle of heart Top expressed in right kidney granulocyte human kidney medullary collecting duct embryo choroid plexus of fourth ventricle Ileal epithelium CA3 field thymus primary motor cortex More reference expression data BioGPS n/a
Gene ontology Molecular function G protein-coupled receptor activity peptide binding signal transducer activity protein binding vasopressin receptor activity Cellular component integral component of membrane endosome Golgi apparatus membrane plasma 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 population proliferation telencephalon development 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: 72.94 – 72.94 Mb PubMed search [3] [4]
Wikidata
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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]

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]