Vasopressin V2 receptor (AVPR2) (AVPR2)

The Vasopressin V2 receptor (AVPR2) is a G protein-coupled receptor primarily expressed in the principal cells of the renal collecting ducts (UniProt P30518). Its fundamental role is the regulation of water homeostasis by mediating the antidiuretic response to arginine vasopressin (AVP) (StatPearls, Vasopressin). Upon activation, the receptor triggers a signaling cascade that increases intracellular cAMP, resulting in the insertion of aquaporin-2 water channels into the apical membrane (PubMed, PMC3543066). This process allows for the reabsorption of water from the pro-urine, leading to concentrated urine and maintenance of blood volume (NIH, AVPR2). Dysregulation of AVPR2 signaling is central to several clinical conditions, such as X-linked nephrogenic diabetes insipidus caused by loss-of-function mutations (NCBI Gene 554). Conversely, excessive activation or inappropriate secretion of vasopressin contributes to hyponatremic states like the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) (Mayo Clinic). Therapeutic strategies include the use of V2 agonists like desmopressin for diabetes insipidus and V2 antagonists like tolvaptan for hyponatremia and polycystic kidney disease (DrugBank, DB00872). Terlipressin, a synthetic analogue used in hepatorenal syndrome, acts as a prodrug for lypressin (lysine-vasopressin), which exerts agonistic effects on both V1 and V2 receptors (DrugBank, DB04872).

Other names

Arginine vasopressin receptor 2V2RAntidiuretic hormone receptorADHRDIRDIR3V2 vasopressin receptor

Agonists bind to the V2 receptor, activating the Gs-adenylyl cyclase pathway to increase intracellular cAMP, which triggers the translocation of aquaporin-2 channels to the apical membrane of renal collecting duct cells for water reabsorption (UniProt P30518). Antagonists competitively inhibit this binding to promote aquaresis (solute-free water excretion) (DrugBank DB00872).