Vasopressin receptor

There are three subtypes of vasopressin receptor: V1A (V1), V1B (V3) and V2. The increased intracellular cAMP in the kidney in turn triggers fusion of aquaporin-2-bearing vesicles with the apical plasma membrane of the collecting duct principal cells, increasing water reabsorption. V3 receptor The human V3 receptor (V3R, previously known as V1BR) is a G-protein-coupled pituitary receptor that, because of its scarcity, was only recently characterized. The 424-amino-acid sequence of the V3R has homologies of 45%, 39%, and 45% with the V1R, V2R and oxytocin receptor (OTR), respectively. However, V3R has a pharmacologic profile that distinguishes it from the human V1R and activates several signaling pathways via different G-proteins, depending on the level of receptor expression. ==Function==

Although all three of these proteins are G-protein coupled receptors (GPCRs), activation of AVPR1A and AVPR1B stimulate phospholipase C, while activation of AVPR2 stimulates adenylate cyclase. These three receptors for vasopressin have unique tissue distributions. AVPR1A are expressed in vascular smooth muscle cells, hepatocytes, platelets, brain cells, and uterus cells. AVPR1B are expressed in cells of the anterior pituitary and throughout the brain, especially in the pyramidal neurons of the hippocampal CA2 field. AVPR2 are expressed in the kidney tubule, predominantly in the distal convoluted tubule and collecting ducts, in fetal lung tissue and lung cancer, the last two being associated with alternative splicing. AVPR2 is also expressed in the liver where stimulation releases a variety of clotting factors into the bloodstream. In the kidney, AVPR2's primary function is to respond to arginine vasopressin by stimulating mechanisms that concentrate the urine and maintain water homeostasis in the organism. When the function of AVPR2 is lost, the disease Nephrogenic Diabetes Insipidus (NDI) results. == Antagonists ==

Vasopressin receptor antagonists (VRAs) are drugs that block vasopressin receptors. Most commonly VRAs are used to treat hyponatremia caused by syndrome of inappropriate antidiuretic hormone secretion (SIADH), congestive heart failure (CHF) and cirrhosis. Normally, when osmolality falls below its set point, plasma vasopressin levels become undetectable, and an aquaresis results. In SIADH, vasopressin release is not fully suppressed, despite hypotonicity. In cirrhosis and CHF, impaired delivery of solute to the diluting sites or diminished glomerular filtration rate causes impairment of maximal water-excretory capacity, resulting in persistence of vasopressin release leading to water retention. Vasopressin receptor antagonists include the new class of "vaptan drugs" such as conivaptan, tolvaptan, mozavaptan, lixivaptan, satavaptan etc. == References ==