Wikipedia

Vasopressin receptor

The actions ofvasopressinare mediated by stimulation of tissue-specificG protein-coupled receptors(GPCRs) calledvasopressin receptorsthat are classified into theV1(V1A),V2,andV3(V1B) receptor subtypes.[1]These three subtypes differ in localization, function and signal transduction mechanisms.[2]

arginine vasopressin receptor 1A
Identifiers
SymbolAVPR1A
Alt. symbolsAVPR1
NCBI gene552
HGNC895
OMIM600821
RefSeqNM_000706
UniProtP37288
Other data
LocusChr. 12q14-q15
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StructuresSwiss-model
DomainsInterPro
arginine vasopressin receptor 1B
Identifiers
SymbolAVPR1B
Alt. symbolsAVPR3
NCBI gene553
HGNC896
OMIM600264
RefSeqNM_000707
UniProtP47901
Other data
LocusChr. 1q32
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StructuresSwiss-model
DomainsInterPro
arginine vasopressin receptor 2
Identifiers
SymbolAVPR2
Alt. symbolsDIR3, DIR
NCBI gene897
HGNC897
OMIM300538
RefSeqNM_000054
UniProtP30518
Other data
LocusChr. Xq28
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StructuresSwiss-model
DomainsInterPro

Subtypes

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There are three subtypes of vasopressin receptor: V1A(V1), V1B(V3) and V2.[1]

Subtype (symbol) Signaling pathways Location Function
gene receptor
IUPHAR alternate
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

V1receptor

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Main article:Vasopressin receptor 1A

V1receptors(V1Rs) are found in high density onvascular smooth muscleand causevasoconstrictionby an increase in intracellular calcium via the phosphatidyl–inositol-bisphosphate cascade.[1]Cardiac myocytesalso 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 topolymorphismof 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 theantidiureticaction of vasopressin. Additionally, vasopressin selectively contractsefferent arteriolesprobably through the V1R, but not theafferent arteriole.[1]

V2receptor

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Main article:Vasopressin receptor 2

V2receptor(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 knownantidiureticeffect 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 Gssignaling pathway, which activatescAMP.The V2R continues to activate Gsafter being internalized by β-arrestinrather than being desensitized. This internalized Gssignaling by V2R is explained by the receptors ability to form "mega-complexes" consisting of a single V2R, β-arrestin, and heterotrimeric Gs.[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]

V3receptor

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Main article:Vasopressin receptor 1B

The humanV3receptor(V3R, previously known as V1BR) is a G-protein-coupledpituitaryreceptor 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]

Function

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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 tubuleandcollecting ducts,infetallungtissue andlung cancer,the last two being associated withalternative splicing.AVPR2 is also expressed in the liver where stimulation releases a variety ofclotting factorsinto the bloodstream. In the kidney, AVPR2's primary function is to respond to arginine vasopressin by stimulating mechanisms that concentrate theurineand maintainwaterhomeostasisin the organism. When the function of AVPR2 is lost, the diseaseNephrogenic Diabetes Insipidus(NDI) results.[4]

Antagonists

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Vasopressin receptor antagonists(VRAs) are drugs that block vasopressin receptors. Most commonly VRAs are used to treathyponatremiacaused 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]IncirrhosisandCHF,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,satavaptanetc.

References

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  1. ^abcdefghijklHolmes CL, Landry DW, Granton JT (December 2003)."Science review: Vasopressin and the cardiovascular system part 1--receptor physiology".Crit Care.7(6): 427–34.doi:10.1186/cc2337.PMC374366.PMID14624682.
  2. ^abcdGreenberg A, Verbalis JG (June 2006)."Vasopressin receptor antagonists".Kidney Int.69(12): 2124–30.doi:10.1038/sj.ki.5000432.PMID16672911.
  3. ^Thomsen AR, Plouffe B, Cahill TJ, Shukla AK, Tarrasch JT, Dosey AM, Kahsai AW, Strachan RT, Pani B, Mahoney JP, Huang L, Breton B, Heydenreich FM, Sunahara RK, Skiniotis G, Bouvier M, Lefkowitz RJ (2016)."GPCR-G Protein-β-Arrestin Super-Complex Mediates Sustained G Protein Signaling".Cell.166(4): 907–19.doi:10.1016/j.cell.2016.07.004.PMC5418658.PMID27499021.
  4. ^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.doi:10.1002/jcp.21552.PMID18726898.S2CID20462680.
  5. ^Inhibition by somatostatin of the vasopressin-stimulated adenylate cyclase in a kidney-derived line of cells grown in defined medium. FEBS Letters.https://doi.org/10.1016/0014-5793(84)80304-X
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