Arginine vasopressin receptor 2 (AVPR2) (AVPR2)

The Arginine vasopressin receptor 2 (AVPR2), also referred to as the Antidiuretic hormone receptor, is a G protein-coupled receptor (GPCR) primarily located on the basolateral membrane of the renal collecting ducts [4, 14]. Its fundamental biological role is to mediate the antidiuretic action of arginine vasopressin, a hormone that regulates the body's water balance by promoting the reabsorption of water from the urine [2, 13]. Activation of the receptor triggers a cAMP-dependent signaling cascade that leads to the translocation of aquaporin-2 water channels to the apical membrane, significantly increasing the water permeability of the kidney tubules [7, 11]. Beyond its renal function, AVPR2 is expressed on vascular endothelial cells, where it mediates the release of essential clotting factors, including Factor VIII and von Willebrand factor [4, 15]. Mutations in the AVPR2 gene that result in loss of function cause nephrogenic diabetes insipidus, a condition characterized by the inability to concentrate urine despite adequate hormone levels [14]. Conversely, excessive activation of this receptor pathway is a hallmark of the Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) and is a key factor in the development of hyponatremia in heart failure and cirrhosis [14, 17]. Pharmacologically, AVPR2 is targeted by agonists like desmopressin for the treatment of central diabetes insipidus and nocturnal enuresis, as well as by antagonists known as vaptans to manage water retention and hyponatremia [10, 16]. Tolvaptan, a selective V2 receptor antagonist, is also indicated to slow kidney function decline in patients with autosomal dominant polycystic kidney disease [16]. Careful monitoring of serum sodium levels is required during therapy with AVPR2-modulating drugs to prevent osmotic demyelination syndrome, a severe neurological consequence of rapid sodium correction [15].

Other names

Antidiuretic hormone receptorVasopressin V2 receptorV2RV2 receptorADHRDIR3

V2 receptor agonists like desmopressin bind to the receptor to increase intracellular cAMP, which promotes the translocation of aquaporin-2 channels to the apical membrane for water reabsorption. Conversely, V2 receptor antagonists (vaptans) competitively inhibit this process, leading to the excretion of electrolyte-free water (aquaresis).