Vasopressin receptor 2 (V2R (also AVPR2))

Vasopressin receptor 2 is a G protein-coupled receptor primarily expressed on the basolateral membrane of principal cells within renal collecting ducts. It mediates the antidiuretic action of arginine vasopressin by activating adenylate cyclase through Gs proteins, raising intracellular cAMP levels that trigger insertion of aquaporins into the cell membrane—thereby promoting water reabsorption and concentrating urine. The V2R also has extra‐renal roles such as stimulating release of coagulation factors from vascular endothelium. Mutations can lead to nephrogenic diabetes insipidus by impairing renal response to vasopressin. Pharmacologically, it is targeted by both agonists for conditions like central diabetes insipidus or certain bleeding disorders, and antagonists ("vaptans") for treating hyponatremia associated with SIADH or heart failure. The V2R is also implicated in cancer biology where its modulation affects tumor proliferation and metastasis through antiproliferative signaling pathways involving cAMP/PKA activation.

Other names

Arginine vasopressin receptor 2Antidiuretic hormone receptorRenal-type arginine vasopressin receptorAVPR V2DIRDIR3

Agonists stimulate the V2R to activate Gs proteins → increased adenylate cyclase activity → elevated cAMP → activation of protein kinase A → phosphorylation and insertion of aquaporin channels into the collecting duct membrane for water reabsorption. This underlies their use in central diabetes insipidus or bleeding disorders by increasing factor VIII/von Willebrand factor release from endothelium. Antagonists block this pathway to promote free water excretion ("aquaretic" effect), useful in SIADH or heart failure with hyponatremia. Some drugs act as pharmacoperones to rescue misfolded receptors due to genetic mutations.