Vasopressin V2 receptor (AVPR2)

The Vasopressin V2 receptor (AVPR2) is a G protein-coupled receptor (GPCR) primarily located on the basolateral membrane of the principal cells in the renal collecting ducts [1, 6]. Its central biological role is the regulation of water homeostasis; upon activation by the hormone arginine vasopressin (AVP), it triggers the Gs-adenylyl cyclase-cAMP-PKA signaling pathway, which promotes the translocation of aquaporin-2 (AQP2) water channels to the apical membrane [6, 15]. This mechanism allows for the reabsorption of water from the renal tubules back into the systemic circulation, thereby concentrating the urine and maintaining fluid balance [1, 12]. Dysregulation of AVPR2 is implicated in several pathological states: loss-of-function mutations lead to X-linked nephrogenic diabetes insipidus, while overactivity or inappropriate vasopressin levels contribute to hyponatremia and the progression of Autosomal Dominant Polycystic Kidney Disease (ADPKD) [4, 7, 13]. Drugs such as tolvaptan act as selective antagonists of this receptor, blocking vasopressin-induced water reabsorption to treat hyponatremia and slow cyst growth in ADPKD [1, 3]. However, therapeutic intervention requires careful monitoring due to risks such as rapid sodium correction, which can cause osmotic demyelination syndrome, and potential drug-induced liver injury [1, 5].

Other names

Arginine vasopressin receptor 2V2RAntidiuretic hormone receptorRenal-type arginine vasopressin receptor

Selective competitive antagonism of the Vasopressin V2 receptor, which inhibits the arginine vasopressin-induced activation of adenylyl cyclase and the subsequent cAMP-mediated translocation of aquaporin-2 water channels to the apical membrane of renal collecting duct cells [1, 6].