Vasopressin receptor 2

Vasopressin receptor 2 (V2R) is a protein that in humans is encoded by the AVPR2 gene. It is a member of the vasopressin receptor family and is an important receptor in the renal collecting ducts, which play a significant role in antidiuretic hormone (ADH) homeostasis and water reabsorption. The V2 receptor is primarily activated by arginine vasopressin (AVP), a key hormone involved in the regulation of water, glucose, and salts in the blood.

Function

The V2 receptor is coupled to the G proteins that activate adenylyl cyclase, which in turn increases the levels of cyclic AMP (cAMP) and leads to the insertion of aquaporin-2 water channels into the apical membrane of the kidney's collecting duct cells. This process allows for the reabsorption of water back into the bloodstream, thereby concentrating the urine and reducing urine volume. The action of the V2 receptor is crucial for the body's ability to maintain water balance and respond to hypernatremia or hypovolemia.

Clinical Significance

Mutations in the AVPR2 gene can lead to X-linked nephrogenic diabetes insipidus (NDI), a condition characterized by an inability of the kidney to concentrate urine in response to ADH, leading to excessive urine production and thirst. Treatment options for NDI are limited, focusing mainly on dietary measures and the use of thiazide diuretics.

In addition to its role in NDI, the V2 receptor is a target for the treatment of conditions such as hyponatremia, particularly when associated with heart failure or cirrhosis. Pharmacological agents that act as V2 receptor antagonists, such as tolvaptan, can increase water excretion without causing sodium loss, improving serum sodium levels.

Pharmacology

The pharmacological manipulation of the V2 receptor involves the use of agonists and antagonists. Agonists can be used in the treatment of central diabetes insipidus, whereas antagonists are useful in conditions where water retention is problematic. The development of selective V2 receptor antagonists has been a significant advancement in the treatment of hyponatremia.

Genetics

The AVPR2 gene is located on the X chromosome (Xq28), which explains the X-linked inheritance pattern of diseases associated with this receptor. Genetic testing can confirm a diagnosis of NDI by identifying mutations in the AVPR2 gene.

See Also

• Vasopressin
• Diabetes insipidus
• Aquaporin
• G protein-coupled receptor

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