Arginine vasopressin receptor 2

Arginine vasopressin receptor 2 (AVPR2), also known as the Vasopressin V2 receptor, is a protein that in humans is encoded by the AVPR2 gene located on the X chromosome. This receptor is a member of the vasopressin receptor family and is a key player in the regulation of water reabsorption in the kidneys. It is primarily found in the renal collecting ducts where it mediates the effect of arginine vasopressin (AVP), also known as antidiuretic hormone (ADH), facilitating water reabsorption back into the circulation.

Function

The AVPR2 receptor is activated by arginine vasopressin, leading to a series of intracellular events that ultimately increase the permeability of the collecting duct walls to water. This action is mediated through the activation of the G_s protein, which in turn stimulates adenylyl cyclase to convert ATP to cyclic AMP (cAMP). The increase in cAMP activates protein kinase A (PKA), which then phosphorylates specific proteins in the cells lining the collecting ducts, leading to the insertion of aquaporin-2 water channels into the apical membrane of these cells. As a result, water is reabsorbed from the urine, concentrating it and reducing urine volume.

Clinical Significance

Mutations in the AVPR2 gene can lead to X-linked nephrogenic diabetes insipidus (NDI), a condition characterized by an inability to concentrate urine despite the presence of normal or elevated levels of AVP, leading to excessive urine production and thirst. Treatment options for NDI are limited, focusing mainly on dietary measures and the use of thiazide diuretics to reduce urine output.

In addition to its role in water balance, AVPR2 has been implicated in a variety of other physiological and pathological processes, including roles in bone density regulation, social behavior, and the response to stress.

Pharmacology

Pharmacologically, AVPR2 can be targeted by several types of drugs. Vaptans are a class of non-peptide, orally active AVPR2 antagonists used in the treatment of hyponatremia (low blood sodium levels) associated with conditions like heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Conversely, AVPR2 agonists may be used in the treatment of conditions like NDI, although their use is limited by the underlying receptor mutations in many patients.

See Also

• Vasopressin receptor
• Nephrogenic diabetes insipidus
• Aquaporin-2
• Hyponatremia