Vasopressin V2 receptor (V2R), or arginine vasopressin receptor 2 (AVPR2), is a G-protein-coupled receptor (GPCR), coupled to the stimulatory heterotrimeric GTP-binding protein, G^­_S, that elevates intracellular cAMP through activation of adenylate cyclase^1-3. Like all members, it has seven transmembrane domains, an extracellular N-terminus and intracellular C-terminal tail¹.

AVPR2 is expressed primarily in renal collecting ducts and loop of Henle of the kidney, but also in vascular smooth muscle, where it induces vasodilation. Its ligand is the anti-diuretic hormone (ADH), aka vasopressin; a hormone that originates from the posterior pituitary gland that has key roles in water homeostasis and in hypotension⁵.

Vasopressin triggers a variety of receptors – V1R, V2R, V3R, oxytocin and purinergic receptors, which regulate the physiological water-balance. High levels of inflammatory factors in the blood, such as the case in sepsis, are known to down-regulate the vasopressin receptors³.

Mutations in V2R that prevent the receptor from reaching and anchoring to the cell surface are responsible are detected in diabetes insipidus and heart failure^4,6,7 just to name a few. Interestingly, it was found that female rats possess more V2R mRNA than male rats leading to increased urine osmolality and decreased urine volume in females compared with males – a finding which explains that clinical data according to which females are more prone to suffer from hyponatremia⁴. A recent study also showed that vasopressin interacts with V2R in sperm-cell membranes to enhance ion transport; over expression of the hormone reduced sperm motility, hence V2R also has an important part in male fertility⁸.