The actions ofvasopressin are mediated by stimulation of tissue-specificG protein-coupled receptors (GPCRs) calledvasopressin receptors that are classified into theV₁ (V_1A),V₂, andV₃ (V_1B) receptor subtypes.^[1] These three subtypes differ in localization, function and signal transduction mechanisms.^[2]

There are three subtypes of vasopressin receptor: V_1A (V₁), V_1B (V₃) and V₂.^[1]

V₁ receptors (V₁Rs) are found in high density onvascular smooth muscle and causevasoconstriction by an increase in intracellular calcium via the phosphatidyl–inositol-bisphosphate cascade.^[1]Cardiac myocytes also possess V₁R. Additionally V₁R are located inbrain,testis,superior cervical ganglion,liver,blood vessels, andrenal medulla.^[1]

V₁R is present onplatelets, which upon stimulation induces an increase in intracellular calcium, facilitatingthrombosis. Studies have indicated that due topolymorphism of platelet V₁R there is significant heterogeneity in the aggregation response of normal human platelets tovasopressin.^[1]

V₁Rs are found inkidney, where they occur in high density onmedullary interstitial cells,vasa recta, and epithelial cells of thecollecting duct.^[1] Vasopressin acts on medullary vasculature through V₁R to reduce blood flow to inner medulla without affecting blood flow to outer medulla. V₁Rs on the luminal membrane of the collecting duct limit theantidiuretic action of vasopressin. Additionally, vasopressin selectively contractsefferent arterioles probably through the V₁R, but not theafferent arteriole.^[1]

V₂ receptor (V₂R) differs from V₁R primarily in the number of sites susceptible to N-linked glycosylation; the V₁R has sites at both the amino-terminus and at the extracellular loop, whereas the V₂R has a single site at the extracellular amino-terminus.^[1]

The well knownantidiuretic effect of vasopressin occurs via activation of V₂R.^[1] Vasopressin regulates water excretion from the kidney by increasing the osmotic water permeability of the renalcollecting duct – an effect that is explained by coupling of the V₂R with the G_s signaling pathway, which activatescAMP. The V₂R continues to activate G_s after being internalized by β-arrestin rather than being desensitized. This internalized G_s signaling by V₂R is explained by the receptors ability to form "mega-complexes" consisting of a single V₂R, β-arrestin, and heterotrimeric G_s.^[3] The increased intracellular cAMP in the kidney in turn triggers fusion ofaquaporin-2-bearing vesicles with the apical plasma membrane of the collecting ductprincipal cells, increasing water reabsorption.^[1]

The humanV₃ receptor (V₃R, previously known as V_1BR) is a G-protein-coupledpituitary receptor that, because of its scarcity, was only recently characterized.^[1] The 424-amino-acid sequence of the V₃R has homologies of 45%, 39%, and 45% with the V₁R, V₂R andoxytocin receptor (OTR), respectively. However, V₃R has a pharmacologic profile that distinguishes it from the human V₁R and activates several signaling pathways via differentG-proteins, depending on the level of receptor expression.^[1]

Although all three of these proteins areG-protein coupled receptors (GPCRs), activation of AVPR1A and AVPR1B stimulatephospholipase C, while activation of AVPR2 stimulatesadenylate 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 thekidney tubule, predominantly in thedistal convoluted tubule andcollecting ducts, infetallung tissue andlung cancer, the last two being associated withalternative splicing. AVPR2 is also expressed in the liver where stimulation releases a variety ofclotting factors into the bloodstream. In the kidney, AVPR2's primary function is to respond to arginine vasopressin by stimulating mechanisms that concentrate theurine and maintainwaterhomeostasis in the organism. When the function of AVPR2 is lost, the diseaseNephrogenic Diabetes Insipidus (NDI) results.^[4]

Vasopressin receptor antagonists (VRAs) are drugs that block vasopressin receptors. Most commonly VRAs are used to treathyponatremia caused bysyndrome of inappropriate antidiuretic hormone secretion (SIADH),congestive heart failure (CHF) andcirrhosis.^[2]

Somatostatin is a competitive inhibitor.^[5]

Normally, when osmolality falls below its set point, plasma vasopressin levels become undetectable, and an aquaresis results. InSIADH, vasopressin release is not fully suppressed, despite hypotonicity.^[2] Incirrhosis andCHF, 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.^[2]

Vasopressin receptor antagonists include the new class of "vaptan drugs" such asconivaptan,tolvaptan,mozavaptan,lixivaptan,satavaptan etc.

• "Vasopressin and Oxytocin Receptors".IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived fromthe original on 2016-03-03. Retrieved2007-10-25.
• Vasopressin+Receptors at the U.S. National Library of MedicineMedical Subject Headings (MeSH)

• Genes on human chromosome 12
• Genes on human chromosome 1
• Genes on human chromosome X
• G protein-coupled receptors

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