|arginine vasopressin receptor 1A|
|Locus||Chr. 12 q14-q15|
|arginine vasopressin receptor 1B|
|Locus||Chr. 1 q32|
|arginine vasopressin receptor 2|
|Alt. symbols||DIR3, DIR|
|Locus||Chr. X q28|
The actions of vasopressin are mediated by stimulation of tissue-specific G protein-coupled receptors (GPCRs) called vasopressin receptors that are classified into V1, V2 and V3 subtypes. These three subtypes differ in localization, function and signal transduction mechanisms.
- V1 receptor 1.1
- V2 receptor 1.2
- V3 receptor 1.3
- Function 2
- Antagonists 3
- See also 4
- References 5
- External links 6
There are three subtypes of vasopressin receptor: V1A (V1), V1B (V3) and V2.
|Subtype (symbol)||Signaling pathways||Location||Function|
|AVPR1A||V1A||V1||G protein-coupled, phosphatidylinositol/calcium||vascular smooth muscle, platelet, hepatocytes, myometrium||vasoconstriction, myocardial hypertrophy, platelet aggregation, glycogenolysis, uterine contraction|
|AVPR1B||V1B||V3||G protein-coupled, phosphatidylinositol/calcium||anterior pituitary gland||releases ACTH, prolactin, endorphins|
|AVPR2||V2||V2||Adenylyl cyclase/cAMP||basolateral membrane of collecting duct, vascular endothelium and vascular smooth muscle cell||insertion of AQP-2 water channels into apical membrane, induction of AQP-2 synthesis, releases von Willebrand factor and factor VIII, vasodilation|
V1 receptors (V1Rs) are found in high density on vascular smooth muscle and cause vasoconstriction by an increase in intracellular calcium via the phosphatidyl–inositol-bisphosphonate cascade. Cardiac myocytes also possess V1R. Additionally V1R are located in brain, testis, superior cervical ganglion, liver, blood vessels, and renal medulla.
V1R is present on platelets, which upon stimulation induces an increase in intracellular calcium, facilitating thrombosis. Studies have indicated that due to polymorphism of platelet V1R there is significant heterogeneity in the aggregation response of normal human platelets to vasopressin.
V1Rs are found in kidney, where they occur in high density on medullary interstitial cells, vasa recta, and epithelial cells of the collecting duct. 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 the antidiuretic action of vasopressin. Additionally, vasopressin selectively contracts efferent arterioles probably through the V1R, but not the afferent arteriole.
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.
The well known antidiuretic effect of vasopressin occurs via activation of V2R. Vasopressin regulates water excretion from the kidney by increasing the osmotic water permeability of the renal collecting duct – an effect that is explained by coupling of the V2R with the Gs signaling pathway, which activates cAMP. 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.
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.
Although all three of these proteins are Nephrogenic Diabetes Insipidus (NDI) results.
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.
- Holmes CL, Landry DW, Granton JT (December 2003). "Science review: Vasopressin and the cardiovascular system part 1--receptor physiology". Crit Care 7 (6): 427–34.
- Greenberg A, Verbalis JG (June 2006). "Vasopressin receptor antagonists". Kidney Int. 69 (12): 2124–30.
- Spanakis E, Milord E, Gragnoli C (December 2008). "AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance". J. Cell. Physiol. 217 (3): 605–17.
- "Vasopressin and Oxytocin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- Vasopressin Receptors at the US National Library of Medicine Medical Subject Headings (MeSH)