Vasopressin

{{Short description|Mammalian hormone released from the pituitary gland}}

{{About|the natural peptide in mammals|the medication|Vasopressin (medication)}}

{{distinguish|text=vasopressors generally, of which it is but one example}}

{{infobox drug

| Watchedfields = changed

| verifiedrevid =

| drug_name =

| IUPAC_name = 1-{[(4R,7S,10S,13S,16S,19R)-19-Amino-7-(2-amino-2-oxoethyl)-10-(3-amino-3-oxopropyl)-13-benzyl-16-(4-hydroxybenzyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentaazacycloicosan-4-yl]carbonyl}-L-p rolyl-L-arginylglycinamide

| synonyms= Antidiuretic hormone (ADH); arginine vasopressin (AVP); argipressin

| image = Vasopressin_labeled.png

| width = 250px

| image2 = Arginine_vasopressin3d.png

| pronounce = {{IPAc-en|ˌ|v|eɪ|z|oʊ|ˈ|p|r|ɛ|s|ɪ|n}}

| source_tissues = Supraoptic nucleus; paraventricular nucleus of hypothalamus

| target_tissues = System-wide

| receptors = V_1A, V_1B, V₂, OXTR

| agonists = Felypressin, desmopressin

| antagonists = Diuretics

| bioavailability =

| protein_bound = 1%

| metabolism = Predominantly in the liver and kidneys

| elimination_half-life = 10–20 minutes

| excretion = Urine

| ATC_prefix = H01

| ATC_suffix = BA01

| IUPHAR_ligand = 2168

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 11000-17-2

| PubChem = 644077

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00067

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 559126

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = Y87Y826H08

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D00101

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 9937

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 373742

| PDB_ligand =

| C=46 | H=65 | N=15 | O=12 | S=2

| molecular_weight =

| SMILES = c1ccc(cc1)C[C@H]2C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@H](C(=O)N2)Cc3ccc(cc3)O)N)C(=O)N4CCC[C@H]4C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)N)CC(=O)N)CCC(=O)N

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C46H65N15O12S2

/c47-27-22-74-75-23-33(45(73)61-17-5-9-34(61)44(72)56-28(8-4-16-53-46(51)52)39(67)54-21-37(50)65)60-43(71)32(20-36(49)64)59-40(68)29(14-15-35(48)63)55-41(69)31(18-24-6-2-1-3-7-24)58-42(70)30(57-38(27)66)19-25-10-12-26(62)13-11-25/h1-3,6-7,10-13,27-34,62H,4-5,8-9,14-23,47H2,(H2,48,63)(H2,49,64)(H2,50,65)(H,54,67)(H,55,69)(H,56,72)(H,57,66)(H,58,70)(H,59,68)(H,60,71)(H4,51,52,53)/t27-,28-,29-,30-,31-,32-,33-,34-/m0/s1

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = KBZOIRJILGZLEJ-LGYYRGKSSA-N

| density = 1.6±0.1

|alt=|caption=|type=|MedlinePlus=|legal_status=|licence_EU=|pregnancy_AU=|pregnancy_US=|pregnancy_category=|licence_US=}}

Mammalian vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin,{{cite book | vauthors = Anderson DA | title = Dorland's Illustrated Medical Dictionary | publisher=Elsevier | url = https://books.google.com/books?id=mNACisYwbZoC&q=argipressin | isbn = 978-1-4160-6257-8 | year = 2012 | edition = 32nd}} is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus,{{cite journal | vauthors = Sukhov RR, Walker LC, Rance NE, Price DL, Young WS 3rd | title = Vasopressin and oxytocin gene expression in the human hypothalamus | journal = Journal of Comparative Neurology | volume = 337 | issue = 2 | pages = 295–306 | date = 1993 | pmid = 8277003 | doi = 10.1002/cne.903370210| pmc = 9883978 | s2cid = 35174328 }} and is converted to AVP. It then travels down the axon terminating in the posterior pituitary, and is released from vesicles into the circulation in response to extracellular fluid hypertonicity (hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the circulation from the filtrate in the kidney tubules of the nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure.{{cite book | vauthors = Marieb E | title = Anatomy & physiology | publisher = Pearson Education, Inc | location = Glenview, IL | year = 2014 | isbn = 978-0-321-86158-0 }}{{cite book | vauthors = Caldwell HK, ((Young WS III)) | veditors = Lajtha A, Lim R | title = Handbook of Neurochemistry and Molecular Neurobiology: Neuroactive Proteins and Peptides | edition = 3rd | publisher = Springer | location = Berlin | year = 2006 | chapter = Oxytocin and Vasopressin: Genetics and Behavioral Implications | chapter-url= http://refworks.springer.com/mrw/fileadmin/pdf/Neurochemistry/0387303480C25.PDF | pages = 573–607| isbn = 978-0-387-30348-2 }}{{cite journal | vauthors = Babar SM | title = SIADH associated with ciprofloxacin | journal = The Annals of Pharmacotherapy | volume = 47 | issue = 10 | pages = 1359–63 | date = October 2013 | pmid = 24259701 | doi = 10.1177/1060028013502457 | s2cid = 36759747 }}

A third function is possible. Some AVP may be released directly into the brain from the hypothalamus, and may play an important role in social behavior, sexual motivation and pair bonding, and maternal responses to stress.{{cite journal | vauthors = Insel TR | title = The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior | language = en | journal = Neuron | volume = 65 | issue = 6 | pages = 768–79 | date = March 2010 | pmid = 20346754 | pmc = 2847497 | doi = 10.1016/j.neuron.2010.03.005 }}

Vasopressin induces differentiation of stem cells into cardiomyocytes and promotes heart muscle homeostasis.{{cite journal | vauthors = Costa A, Rossi E, Scicchitano BM, Coletti D, Moresi V, Adamo S | title = Neurohypophyseal Hormones: Novel Actors of Striated Muscle Development and Homeostasis | journal = European Journal of Translational Myology | volume = 24 | issue = 3 | pages = 3790 | date = September 2014 | pmid = 26913138 | pmc = 4756744 | doi = 10.4081/bam.2014.3.217| department = review }}

It has a very short half-life, between 16 and 24 minutes.

Physiology

=Function=

Vasopressin regulates the tonicity of body fluids. It is released from the posterior pituitary in response to hypertonicity and causes the kidneys to reabsorb solute-free water and return it to the circulation from the tubules of the nephron, thus returning the tonicity of the body fluids toward normal. An incidental consequence of this renal reabsorption of water is concentrated urine and reduced urine volume. AVP released in high concentrations may also raise blood pressure by inducing moderate vasoconstriction.{{cite book | vauthors = Cuzzo B, Padala SA, Lappin SL |title=StatPearls |date=2024 |publisher=StatPearls Publishing |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK526069/ |chapter=Physiology, Vasopressin |pmid=30252325 }}

AVP also may have a variety of neurological effects on the brain. It may influence pair-bonding in voles. The high-density distributions of vasopressin receptor AVPr1a in prairie vole ventral forebrain regions have been shown to facilitate and coordinate reward circuits during partner preference formation, critical for pair bond formation.{{cite journal | vauthors = Lim MM, Young LJ | title = Vasopressin-dependent neural circuits underlying pair bond formation in the monogamous prairie vole | journal = Neuroscience | volume = 125 | issue = 1 | pages = 35–45 | year = 2004 | pmid = 15051143 | doi = 10.1016/j.neuroscience.2003.12.008 | s2cid = 16210017 }}

A very similar substance, lysine vasopressin (LVP) or lypressin, has the same function in pigs and its synthetic version was used in human AVP deficiency, although it has been largely replaced by desmopressin.{{Cite web|vauthors = Chapman IM, ((Professor of Medicine, Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital))|url=http://www.merckmanuals.com/professional/endocrine-and-metabolic-disorders/pituitary-disorders/central-diabetes-insipidus#v26379947|title=Central Diabetes Insipidus|website=MSD|publisher= Merck & Co. Inc.}}

==Kidney==

Vasopressin has three main effects which are:

Increasing the water permeability of distal convoluted tubule (DCT) and cortical collecting tubules (CCT), as well as outer and inner medullary collecting duct (OMCD & IMCD) in the kidney, thus allowing water reabsorption and excretion of more concentrated urine, i.e., antidiuresis. This occurs through increased transcription and insertion of water channels (Aquaporin-2) into the apical membrane of collecting tubule and collecting duct epithelial cells.{{cite book | title = Medical Physiology | vauthors = Boron WR, Boulpaep EL | isbn = 978-1-4557-4377-3 | edition = Third | location = Philadelphia, PA | publisher = Elsevier | oclc = 951680737 |date = 2016-05-05}} Aquaporins allow water to move down their osmotic gradient and out of the nephron, increasing the amount of water re-absorbed from the filtrate (forming urine) back into the bloodstream. This effect is mediated by V2 receptors. Vasopressin also increases the concentration of calcium in the collecting duct cells, by episodic release from intracellular stores. Vasopressin, acting through cAMP, also increases transcription of the aquaporin-2 gene, thus increasing the total number of aquaporin-2 molecules in collecting duct cells.{{cite journal | vauthors = Wilson JL, Miranda CA, Knepper MA| title = Vasopressin and the Regulation of Aquaporin-2 | journal = Clinical and Experimental Nephrology | year = 2013 | volume = 17 | issue = 6 | pages = 10.1007/s10157-013–0789-5 | doi = 10.1007/s10157-013-0789-5 | pmid = 23584881 | pmc = 3775849 }}
Increasing permeability of the inner medullary portion of the collecting duct to urea by regulating the cell surface expression of urea transporters,{{cite journal | vauthors = Sands JM, Blount MA, Klein JD | title = Regulation of renal urea transport by vasopressin | journal = Transactions of the American Clinical and Climatological Association | volume = 122 | pages = 82–92 | year = 2011 | pmid = 21686211 | pmc = 3116377 }} which facilitates its reabsorption into the medullary interstitium as it travels down the concentration gradient created by removing water from the connecting tubule, cortical collecting duct, and outer medullary collecting duct.
Acute increase of sodium absorption across the ascending loop of Henle. This adds to the countercurrent multiplication which aids in proper water reabsorption later in the distal tubule and collecting duct.{{cite journal | vauthors = Knepper MA, Kim GH, Fernández-Llama P, Ecelbarger CA | title = Regulation of thick ascending limb transport by vasopressin | journal = Journal of the American Society of Nephrology | volume = 10 | issue = 3 | pages = 628–34 | date = March 1999 | doi = 10.1681/ASN.V103628 | pmid = 10073614 | doi-access = free }}

The hormone vasopressin also stimulates the activity of NKCC2. Vasopressin stimulates sodium chloride reabsorption in the thick ascending limb of the nephron by activating signaling pathways. Vasopressin increases the traffic of NKCC2 to the membrane and phosphorylates some serine and threonine sites on the cytoplasmic N-terminal of the NKCC2 located in the membrane, increasing its activity. Increased NKCC2 activity aids in water reabsorption in the collecting duct through aquaporin 2 channels by creating a hypo-osmotic filtrate.{{cite journal | vauthors = Rieg T, Tang T, Uchida S, Hammond HK, Fenton RA, Vallon V | title = Adenylyl cyclase 6 enhances NKCC2 expression and mediates vasopressin-induced phosphorylation of NKCC2 and NCC | journal = Am. J. Pathol. | volume = 182 | issue = 1 | pages = 96–106 | date = January 2013 | pmid = 23123217 | pmc = 3532715 | doi = 10.1016/j.ajpath.2012.09.014 }}{{cite journal | vauthors = Ares GR, Caceres PS, Ortiz PA | title = Molecular regulation of NKCC2 in the thick ascending limb | journal = Am. J. Physiol. Renal Physiol. | volume = 301 | issue = 6 | pages = F1143–59 | date = December 2011 | pmid = 21900458 | pmc = 3233874 | doi = 10.1152/ajprenal.00396.2011 }}

==Central nervous system==

Vasopressin released within the brain may have several actions:

Vasopressin is released into the brain in a circadian rhythm by neurons of the suprachiasmatic nucleus.{{cite journal | vauthors = Forsling ML, Montgomery H, Halpin D, Windle RJ, Treacher DF | title = Daily patterns of secretion of neurohypophysial hormones in man: effect of age | journal = Experimental Physiology | volume = 83 | issue = 3 | pages = 409–18 | date = May 1998 | pmid = 9639350 | doi = 10.1113/expphysiol.1998.sp004124 | s2cid = 2295415 | doi-access = free }}
Vasopressin released from posterior pituitary is associated with nausea.{{cite journal | vauthors = Magtanong E | title = What Is Nausea? A Historical Analysis of Changing Views | journal = Auton Neurosci| year = 2017| volume = 202 | pages = 5–17 | doi = 10.1016/j.autneu.2016.07.003 | pmid = 27450627| pmc = 5203950 }}
Recent evidence suggests that vasopressin may have analgesic effects. The analgesia effects of vasopressin were found to be dependent on both stress and sex.{{cite journal | vauthors = Wiltshire T, Maixner W, Diatchenko L | title = Relax, you won't feel the pain | journal = Nature Neuroscience | volume = 14 | issue = 12 | pages = 1496–7 | date = December 2011 | pmid = 22119947 | doi = 10.1038/nn.2987 | s2cid = 205434100 }}

=Regulation=

== Gene regulation ==

Vasopressin is regulated by AVP gene expression which is managed by major clock controlled genes. In this circadian circuit known as the transcription-translation feedback loop (TTFL), Per2 protein accumulates and is phosphorylated by CK1E. Per2 subsequently inhibits the transcription factors Clock and BMAL1 in order to reduce Per2 protein levels in the cell.{{cite journal | vauthors = Dunlap JC | title = Molecular bases for circadian clocks | journal = Cell | volume = 96 | issue = 2 | pages = 271–90 | date = January 1999 | pmid = 9988221 | doi = 10.1016/s0092-8674(00)80566-8 | s2cid = 14991100 | doi-access = free }} At the same time, Per2 also inhibits the transcription factors for the AVP gene in order to regulate its expression, the expression of vasopressin, and other AVP gene products.{{cite journal | vauthors = Jin X, Shearman LP, Weaver DR, Zylka MJ, de Vries GJ, Reppert SM | title = A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock | journal = Cell | volume = 96 | issue = 1 | pages = 57–68 | date = January 1999 | pmid = 9989497 | doi = 10.1016/s0092-8674(00)80959-9 | s2cid = 6916996 | doi-access = free }}

Many factors influence the secretion of vasopressin:

Ethanol (alcohol) reduces the calcium-dependent secretion of AVP by blocking voltage-gated calcium channels in neurohypophyseal nerve terminals in rats.{{cite journal | vauthors = Wang XM, Dayanithi G, Lemos JR, Nordmann JJ, Treistman SN | title = Calcium currents and peptide release from neurohypophysial terminals are inhibited by ethanol | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 259 | issue = 2 | pages = 705–11 | date = November 1991 | doi = 10.1016/S0022-3565(25)20514-6 | pmid = 1941619 }}
Angiotensin II stimulates AVP secretion, in keeping with its general pressor and pro-volumic effects on the body.{{cite journal | vauthors = Matsukawa T, Miyamoto T | title = Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans | journal = American Journal of Physiology. Regulatory, Integrative and Comparative Physiology | volume = 300 | issue = 3 | pages = R624–9 | date = March 2011 | pmid = 21123762 | doi = 10.1152/ajpregu.00324.2010 }}
Atrial natriuretic peptide inhibits AVP secretion, in part by inhibiting Angiotensin II-induced stimulation of AVP secretion.
Cortisol inhibits secretion of antidiuretic hormone.{{cite book|author=Collège des enseignants d'endocrinologie, diabète et maladie|title=Endocrinologie, diabétologie et maladies métaboliques|date=2012-01-30|publisher=Elsevier Masson|isbn=978-2-294-72233-2}}

=Production and secretion=

The physiological stimulus for secretion of vasopressin is increased osmolality of the plasma, monitored by the hypothalamus. A decreased arterial blood volume, (such as can occur in cirrhosis, nephrosis, and heart failure), stimulates secretion, even in the face of decreased osmolality of the plasma: it supersedes osmolality, but

with a milder effect. In other words, the unloading of arterial baroreceptors when the arterial blood volume is low stimulates vasopressin secretion despite the presence of hypoosmolality (hyponatremia).{{cite journal | vauthors = Garrahy A, Thompston CJ | title = General Principles, Diabetes, Metabolism, Obesity, Gastrointestinal Hormones, Aging, Endocrine Toxicology | journal = Encyclopedia of Endocrine Diseases | volume = 1 | issue = 2 | pages = 969–974 | date = 2019}}

The AVP that is measured in peripheral blood is almost all derived from secretion from the posterior pituitary gland (except in cases of AVP-secreting tumours). Vasopressin is produced by magnocellular neurosecretory neurons in the paraventricular nucleus of hypothalamus (PVN) and supraoptic nucleus (SON). It then travels down the axon through the infundibulum within neurosecretory granules that are found within Herring bodies, localized swellings of the axons and nerve terminals. These carry the peptide directly to the posterior pituitary gland, where it is stored until released into the blood.

There are other sources of AVP, beyond the hypothalamic magnocellular neurons. For example, AVP is also synthesized by parvocellular neurosecretory neurons of the PVN, transported and released at the median eminence, from which it travels through the hypophyseal portal system to the anterior pituitary, where it stimulates corticotropic cells synergistically with CRH to produce ACTH (by itself it is a weak secretagogue).{{cite journal | vauthors = Salata RA, Jarrett DB, Verbalis JG, Robinson AG | title = Vasopressin stimulation of adrenocorticotropin hormone (ACTH) in humans. In vivo bioassay of corticotropin-releasing factor (CRF) which provides evidence for CRF mediation of the diurnal rhythm of ACTH | journal = The Journal of Clinical Investigation | volume = 81 | issue = 3 | pages = 766–74 | date = March 1988 | pmid = 2830315 | pmc = 442524 | doi = 10.1172/JCI113382 }}

= Vasopressin during surgery and anaesthesia =

Vasopressin concentration is used to measure surgical stress for evaluation of surgical techniques. Plasma vasopressin concentration is elevated by noxious stimuli,{{cite journal | vauthors = Day TA, Sibbald JR | title = Noxious somatic stimuli excite neurosecretory vasopressin cells via A1 cell group | journal = The American Journal of Physiology | volume = 258 | issue = 6 Pt 2 | pages = R1516-20 | date = June 1990 | pmid = 2360697 | doi = 10.1152/ajpregu.1990.258.6.R1516 }}{{cite journal | vauthors = Höglund OV, Hagman R, Olsson K, Olsson U, Lagerstedt AS | title = Intraoperative changes in blood pressure, heart rate, plasma vasopressin, and urinary noradrenalin during elective ovariohysterectomy in dogs: repeatability at removal of the 1st and 2nd ovary | journal = Veterinary Surgery | volume = 43 | issue = 7 | pages = 852–9 | date = October 2014 | pmid = 25130060 | doi = 10.1111/j.1532-950X.2014.12264.x }} predominantly during abdominal surgery,{{cite journal | vauthors = Goldmann A, Hoehne C, Fritz GA, Unger J, Ahlers O, Nachtigall I, Boemke W | title = Combined vs. Isoflurane/Fentanyl anesthesia for major abdominal surgery: Effects on hormones and hemodynamics | journal = Medical Science Monitor | volume = 14 | issue = 9 | pages = CR445-52 | date = September 2008 | pmid = 18758414 }}{{cite journal | vauthors = Furuya K, Shimizu R, Hirabayashi Y, Ishii R, Fukuda H | title = Stress hormone responses to major intra-abdominal surgery during and immediately after sevoflurane-nitrous oxide anaesthesia in elderly patients | journal = Canadian Journal of Anaesthesia | volume = 40 | issue = 5 Pt 1 | pages = 435–9 | date = May 1993 | pmid = 8390330 | doi = 10.1007/BF03009513 | doi-access = free }}{{cite journal | vauthors = Haas M, Glick SM | title = Radioimmunoassayable plasma vasopressin associated with surgery | journal = Archives of Surgery | volume = 113 | issue = 5 | pages = 597–600 | date = May 1978 | pmid = 646620 | doi = 10.1001/archsurg.1978.01370170059011 }} especially at gut manipulation, traction of viscera,{{cite journal | vauthors = Nussey SS, Page SR, Ang VT, Jenkins JS | title = The response of plasma oxytocin to surgical stress | journal = Clinical Endocrinology | volume = 28 | issue = 3 | pages = 277–82 | date = March 1988 | pmid = 3168310 | doi = 10.1111/j.1365-2265.1988.tb01213.x | s2cid = 37668345 }}{{cite journal | vauthors = Melville RJ, Forsling ML, Frizis HI, LeQuesne LP | title = Stimulus for vasopressin release during elective intra-abdominal operations | journal = The British Journal of Surgery | volume = 72 | issue = 12 | pages = 979–82 | date = December 1985 | pmid = 4084755 | doi = 10.1002/bjs.1800721215 | s2cid = 43764321 }}{{cite journal | vauthors = Moran WH, Miltenberger FW, Shuayb WA, Zimmermann B | title = The Relationship of Antidiuretic Hormone Secretion to Surgical Stress | journal = Surgery | volume = 56 | pages = 99–108 | date = July 1964 | pmid = 14175989 }} as well as abdominal insufflation with carbon dioxide during laparoscopic surgery.{{cite journal | vauthors = Gutt CN, Oniu T, Mehrabi A, Schemmer P, Kashfi A, Kraus T, Büchler MW | title = Circulatory and respiratory complications of carbon dioxide insufflation | journal = Digestive Surgery | volume = 21 | issue = 2 | pages = 95–105 | date = 2004 | pmid = 15010588 | doi = 10.1159/000077038 | s2cid = 3369276 | id = {{ProQuest|223606053}} | doi-access = free }}{{cite journal | vauthors = Nguyen NT, Wolfe BM | title = The physiologic effects of pneumoperitoneum in the morbidly obese | journal = Annals of Surgery | volume = 241 | issue = 2 | pages = 219–226 | date = February 2005 | pmid = 15650630 | pmc = 1356906 | doi = 10.1097/01.sla.0000151791.93571.70 }}

= Receptors =

Types of AVP receptors and their actions:

class="wikitable" ! Type !! Second messenger system !! Locations !! Actions ! Agonists ! Antagonists
AVPR1A	Phosphatidylinositol/calcium	Liver, kidney, peripheral vasculature, brain	Vasoconstriction, glycogen breakdown,{{cite book\|isbn=978-0-8153-4455-1\|title=Essential Cell Biology \| vauthors = Alberts B, Bray D, Hopkin K, Johnson AD, Lewis J, Roberts K \|date=2014 \|publisher=Garland Science }} platelet aggregation, and release of factor VIII and von Willebrand factor; social recognition,{{cite journal \| vauthors = Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ \| title = Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice \| journal = Neuropsychopharmacology \| volume = 29 \| issue = 3 \| pages = 483–93 \| date = March 2004 \| pmid = 14647484 \| doi = 10.1038/sj.npp.1300360 \| doi-access = free }} circadian tau{{cite journal \| vauthors = Wersinger SR, Caldwell HK, Martinez L, Gold P, Hu SB, Young WS \| title = Vasopressin 1a receptor knockout mice have a subtle olfactory deficit but normal aggression \| journal = Genes, Brain and Behavior \| volume = 6 \| issue = 6 \| pages = 540–51 \| date = August 2007 \| pmid = 17083331 \| doi = 10.1111/j.1601-183X.2006.00281.x \| s2cid = 29923520 \| doi-access = free }} \|Felypressin \|
AVPR1B or AVPR3	Phosphatidylinositol/calcium	Pituitary gland, brain	Adrenocorticotropic hormone secretion in response to stress;{{cite journal \| vauthors = Lolait SJ, Stewart LQ, Jessop DS, Young WS, O'Carroll AM \| title = The hypothalamic-pituitary-adrenal axis response to stress in mice lacking functional vasopressin V1b receptors \| journal = Endocrinology \| volume = 148 \| issue = 2 \| pages = 849–56 \| date = February 2007 \| pmid = 17122081 \| pmc = 2040022 \| doi = 10.1210/en.2006-1309 }} social interpretation of olfactory cues{{cite journal \| vauthors = Wersinger SR, Kelliher KR, Zufall F, Lolait SJ, O'Carroll AM, Young WS \| title = Social motivation is reduced in vasopressin 1b receptor null mice despite normal performance in an olfactory discrimination task \| journal = Hormones and Behavior \| volume = 46 \| issue = 5 \| pages = 638–45 \| date = December 2004 \| pmid = 15555506 \| doi = 10.1016/j.yhbeh.2004.07.004 \| s2cid = 38444963 \| url = https://zenodo.org/record/1259471 }} \| \|
AVPR2	Adenylate cyclase/cAMP	Basolateral membrane of the cells lining the collecting ducts of the kidneys (especially the cortical and outer medullary collecting ducts)	Insertion of aquaporin-2 (AQP2) channels (water channels). This allows water to be reabsorbed down an osmotic gradient, and so the urine is more concentrated. Release of von Willebrand factor and surface expression of P-selectin through exocytosis of Weibel-Palade bodies from endothelial cells{{cite journal \| vauthors = Kanwar S, Woodman RC, Poon MC, Murohara T, Lefer AM, Davenpeck KL, Kubes P \| title = Desmopressin induces endothelial P-selectin expression and leukocyte rolling in postcapillary venules \| journal = Blood \| volume = 86 \| issue = 7 \| pages = 2760–6 \| date = October 1995 \| doi = 10.1182/blood.V86.7.2760.2760 \| pmid = 7545469 \| url = http://bloodjournal.hematologylibrary.org/cgi/reprint/86/7/2760 \| doi-access = free }}{{cite journal \| vauthors = Kaufmann JE, Oksche A, Wollheim CB, Günther G, Rosenthal W, Vischer UM \| title = Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP \| journal = The Journal of Clinical Investigation \| volume = 106 \| issue = 1 \| pages = 107–16 \| date = July 2000 \| pmid = 10880054 \| pmc = 314363 \| doi = 10.1172/JCI9516 }} \|AVP, desmopressin \|"-vaptan" diuretics, i.e. tolvaptan

=Structure and relation to oxytocin=

File:vasopressin labeled.png at the 8th amino acid position. Lysine vasopressin differs only in having a lysine in this position.]]

File:Oxytocin with labels.png. Differs from AVP at only the 3rd and 8th position.]]

The vasopressins are peptides consisting of nine amino acids (nonapeptides). The amino acid sequence of arginine vasopressin (argipressin) is Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH₂, with the cysteine residues forming a disulfide bond and the C-terminus of the sequence converted to a primary amide.{{cite book|url=https://books.google.com/books?id=BBLRUI4aHhkC&q=vasopressin+oxytocin+amino+acid+sequence&pg=PA1833|title=Tietz Textbook of Clinical Chemistry and Molecular Diagnostics| vauthors = Burtis CA, Ashwood ER, Bruns DE |publisher=Elsevier Health Sciences|year=2012|isbn=978-1-4557-5942-2|edition=5th|page=1833 }} Lysine vasopressin (lypressin) has a lysine in place of the arginine as the eighth amino acid, and is found in pigs and some related animals, whereas arginine vasopressin is found in humans.{{cite book |doi=10.1016/B978-0-7506-0167-2.50010-8 |chapter=Polyuria and Disorders of Thirst |chapter-url={{Google books|P3XbAgAAQBAJ|page=76|plainurl=yes}} |title=Scientific Foundations of Biochemistry in Clinical Practice |edition=2nd |pages=76–102 |year=1994 |publisher=Butterworth-Heinemann | vauthors = Donaldson D |isbn=978-0-7506-0167-2 | veditors = Williams DL, Marks V }}

The structure of oxytocin is very similar to that of the vasopressins: It is also a nonapeptide with a disulfide bridge and its amino acid sequence differs at only two positions. The two genes are located on the same chromosome separated by a relatively small distance of less than 15,000 bases in most species. The magnocellular neurons that secrete vasopressin are adjacent to magnocellular neurons that secrete oxytocin, and are similar in many respects. The similarity of the two peptides can cause some cross-reactions: oxytocin has a slight antidiuretic function, and high levels of AVP can cause uterine contractions.{{cite journal | vauthors = Li C, Wang W, Summer SN, Westfall TD, Brooks DP, Falk S, Schrier RW | title = Molecular mechanisms of antidiuretic effect of oxytocin | journal = Journal of the American Society of Nephrology | volume = 19 | issue = 2 | pages = 225–32 | date = February 2008 | pmid = 18057218 | pmc = 2396735 | doi = 10.1681/ASN.2007010029 }}{{cite journal | vauthors = Joo KW, Jeon US, Kim GH, Park J, Oh YK, Kim YS, Ahn C, Kim S, Kim SY, Lee JS, Han JS | title = Antidiuretic action of oxytocin is associated with increased urinary excretion of aquaporin-2 | journal = Nephrology, Dialysis, Transplantation | volume = 19 | issue = 10 | pages = 2480–6 | date = October 2004 | pmid = 15280526 | doi = 10.1093/ndt/gfh413 | doi-access = }}

Comparison of vasopressin and oxytocin neuropeptide families:

colspan="3" \| Vertebrate Oxytocin Family
class="wikitable" width="80%" ! colspan="3" \| Vertebrate Vasopressin Family
style="width:25em" \|Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH₂	Argipressin (AVP, ADH)	Most mammals
Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Lys-Gly-NH₂	Lypressin (LVP)	Pigs, hippos, warthogs, some marsupials
Cys-Phe-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH₂	Phenypressin	Some marsupials
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Arg-Gly-NH₂	Vasotocin†	Non-mammals
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH₂	Oxytocin (OXT)	Most mammals, ratfish
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Pro-Gly-NH₂	Prol-Oxytocin	Some New World monkeys, northern tree shrews
Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Ile-Gly-NH₂	Mesotocin	Most marsupials, all birds, reptiles, amphibians, lungfishes, coelacanths
Cys-Tyr-Ile-Gln-Ser-Cys-Pro-Ile-Gly-NH₂	Seritocin	Frogs
Cys-Tyr-Ile-Ser-Asn-Cys-Pro-Ile-Gly-NH₂	Isotocin	Bony fishes
Cys-Tyr-Ile-Ser-Asn-Cys-Pro-Gln-Gly-NH₂	Glumitocin	skates
Cys-Tyr-Ile-Asn/Gln-Asn-Cys-Pro-Leu/Val-Gly-NH₂	Various tocins	Sharks
colspan="3" \| Invertebrate VP/OT Superfamily
Cys-Leu-Ile-Thr-Asn-Cys-Pro-Arg-Gly-NH₂	Inotocin	Locust
Cys-Phe-Val-Arg-Asn-Cys-Pro-Thr-Gly-NH₂	Annetocin	Earthworm
Cys-Phe-Ile-Arg-Asn-Cys-Pro-Lys-Gly-NH₂	Lys-Connopressin	Geography & imperial cone snail, pond snail, sea hare, leech
Cys-Ile-Ile-Arg-Asn-Cys-Pro-Arg-Gly-NH₂	Arg-Connopressin	Striped cone snail
Cys-Tyr-Phe-Arg-Asn-Cys-Pro-Ile-Gly-NH₂	Cephalotocin	Octopus
Cys-Phe-Trp-Thr-Ser-Cys-Pro-Ile-Gly-NH₂	Octopressin	Octopus
colspan="3" \| †Vasotocin is the evolutionary progenitor of all the vertebrate neurohypophysial hormones.{{cite journal\|date=July 1995\|title=The neurohypophysial endocrine regulatory cascade: precursors, mediators, receptors, and effectors\|journal=Frontiers in Neuroendocrinology\|volume=16\|issue=3\|pages=237–89\|doi=10.1006/frne.1995.1009\|pmid=7556852\|vauthors=Acher R, Chauvet J\|s2cid=12739464}}

Medical use

Vasopressin is used to manage anti-diuretic hormone deficiency. Vasopressin is used to treat diabetes insipidus related to low levels of antidiuretic hormone. It is available as Pressyn.{{cite web|url=http://davisplus.fadavis.com/3976/meddeck/pdf/vasopressin.pdf|title=Vasopressin|date=2017|publisher=F.A. Davis Company|access-date=2017-03-13}}{{dead link|date=March 2021}}

Vasopressin has off-label uses and is used in the treatment of vasodilatory shock, gastrointestinal bleeding, ventricular tachycardia and ventricular fibrillation.

Vasopressin agonists are used therapeutically in various conditions, and its long-acting synthetic analogue desmopressin is used in conditions featuring low vasopressin secretion, as well as for control of bleeding (in some forms of von Willebrand disease and in mild haemophilia A) and in extreme cases of bedwetting by children. Terlipressin and related analogues are used as vasoconstrictors in certain conditions. Use of vasopressin analogues for esophageal varices commenced in 1970.{{cite journal | vauthors = Baum S, Nusbaum M | title = The control of gastrointestinal hemorrhage by selective mesenteric arterial infusion of vasopressin | journal = Radiology | volume = 98 | issue = 3 | pages = 497–505 | date = March 1971 | pmid = 5101576 | doi = 10.1148/98.3.497 }}

Vasopressin infusions are also used as second line therapy for septic shock patients not responding to fluid resuscitation or infusions of catecholamines (e.g., dopamine or norepinephrine) to increase the blood pressure while sparing the use of catecholamines. These argipressins have much shorter elimination half-life (around 20 minutes) comparing to synthetic non-arginine vasopresines with much longer elimination half-life of many hours. Further, argipressins act on V1a, V1b, and V2 receptors which consequently lead to higher eGFR and lower vascular resistance in the lungs. A number of injectable arginine vasopressins are currently in clinical use in the United States and in Europe.

=Pharmacokinetics=

Vasopressin is administered through an intravenous device, intramuscular injection or a subcutaneous injection. The duration of action depends on the mode of administration and ranges from thirty minutes to two hours. It has a half life of ten to twenty minutes. It is widely distributed throughout the body and remains in the extracellular fluid. It is degraded by the liver and excreted through the kidneys. Arginin vasopressins for use in septic shock are intended for intravenous use only.

= Side effects =

The most common side effects during treatment with vasopressin are dizziness, angina, chest pain, abdominal cramps, heartburn, nausea, vomiting, trembling, fever, water intoxication, pounding sensation in the head, diarrhoea, sweating, paleness, and flatulence. The most severe adverse reactions are myocardial infarction and hypersensitivity.

=Contraindications=

The use of lysine vasopressin is contraindicated in the presence of hypersensitivity to beef or pork proteins, increased BUN and chronic kidney failure. It is recommended that it be cautiously used in instances of perioperative polyuria, sensitivity to the drug, asthma, seizures, heart failure, a comatose state, migraine headaches, and cardiovascular disease.

=Interactions=

alcohol - may lower the antidiuretic effect
carbamazepine, chloropropamide, clofibrate, tricyclic antidepressants and fludrocortisone may raise the antidiuretic effect
lithium, demeclocycline, heparin or norepinephrine may lower the antidiuretic effect
vasopressor effect may be higher with the concurrent use of ganglionic blocking medications

=Deficiency=

Decreased AVP release (neurogenic — i.e. due to alcohol intoxication or tumour) or decreased renal sensitivity to AVP (nephrogenic, i.e. by mutation of V2 receptor or AQP) leads to diabetes insipidus, a condition featuring hypernatremia (increased blood sodium concentration), polyuria (excess urine production), and polydipsia (thirst).

=Excess=

{{Main|Syndrome of inappropriate antidiuretic hormone secretion}}

Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in turn can be caused by a number of problems. Some forms of cancer can cause SIADH, particularly small cell lung carcinoma but also a number of other tumors. A variety of diseases affecting the brain or the lung (infections, bleeding) can be the driver behind SIADH. A number of drugs have been associated with SIADH, such as certain antidepressants (serotonin reuptake inhibitors and tricyclic antidepressants), the anticonvulsant carbamazepine, oxytocin (used to induce and stimulate labor), and the chemotherapy drug vincristine. It has also been associated with fluoroquinolones (including ciprofloxacin and moxifloxacin). Finally, it can occur without a clear explanation.{{cite journal|date=November 2007|title=Hyponatremia treatment guidelines 2007: expert panel recommendations|journal=The American Journal of Medicine|volume=120|issue=11 Suppl 1|pages=S1–21|doi=10.1016/j.amjmed.2007.09.001|pmid=17981159|vauthors=Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH|citeseerx=10.1.1.499.7585}} Hyponatremia can be treated pharmaceutically through the use of vasopressin receptor antagonists.

History

Vasopressin was elucidated and synthesized for the first time by Vincent du Vigneaud.

Animal studies

Evidence for an effect of AVP on monogamy vs polygamy comes from experimental studies in several species, which indicate that the precise distribution of vasopressin and vasopressin receptors in the brain is associated with species-typical patterns of social behavior. In particular, there are consistent differences between monogamous species and polygamous species in the distribution of AVP receptors, and sometimes in the distribution of vasopressin-containing axons, even when closely related species are compared.{{cite journal|date=October 2009|title=The neuroendocrinology of the social brain|journal=Frontiers in Neuroendocrinology|volume=30|issue=4|pages=425–8|doi=10.1016/j.yfrne.2009.06.002|pmid=19596026|vauthors=Young LJ|s2cid=31960688}}

Human studies

Vasopressin has shown nootropic effects on pain perception and cognitive function.{{cite journal | vauthors = Mavani GP, DeVita MV, Michelis MF | title = A review of the nonpressor and nonantidiuretic actions of the hormone vasopressin | journal = Frontiers in Medicine | volume = 2 | pages = 19 | date = 2015 | pmid = 25853137 | pmc = 4371647 | doi = 10.3389/fmed.2015.00019 | doi-access = free }} Vasopressin also plays a role in autism, major depressive disorder, bipolar disorder, and schizophrenia.{{cite journal | vauthors = Iovino M, Messana T, De Pergola G, Iovino E, Dicuonzo F, Guastamacchia E, Giagulli VA, Triggiani V | title = The Role of Neurohypophyseal Hormones Vasopressin and Oxytocin in Neuropsychiatric Disorders | journal = Endocrine, Metabolic & Immune Disorders Drug Targets | volume = 18 | issue = 4 | pages = 341–347 | date = 2018 | pmid = 29468985 | doi = 10.2174/1871530318666180220104900 | s2cid = 3465601 }}