Vasopressin

Source: Wikipedia, the free encyclopedia.
This article is about the natural peptide in humans. For the medication, see Vasopressin (medication).
Not to be confused with vasopressors generally, of which it is but one example.
Vasopressin
Physiological data
Source tissuesSupraoptic nucleus; paraventricular nucleus of hypothalamus
Target tissuesSystem-wide
ReceptorsV1A, V1B, V2, OXTR
AgonistsFelypressin, desmopressin
AntagonistsDiuretics
MetabolismPredominantly in the liver and kidneys
Pharmacokinetic data
Protein binding1%
MetabolismPredominantly in the liver and kidneys
Elimination half-life10–20 minutes
ExcretionUrine
Identifiers
  • 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
JSmol)
Density1.6±0.1 g/cm3
  • 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
  • InChI=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 checkY
  • Key:KBZOIRJILGZLEJ-LGYYRGKSSA-N checkY
AVP
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000101200

ENSMUSG00000037727

UniProt

P01185

P35455

RefSeq (mRNA)

NM_000490

NM_009732

RefSeq (protein)

NP_000481

NP_033862

Location (UCSC)Chr 20: 3.08 – 3.08 MbChr 2: 130.42 – 130.42 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin,[5] is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus,[6] 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.[7][8][9]

A third function is possible. Some AVP may be released directly into the

sexual motivation and pair bonding, and maternal responses to stress.[10]

Vasopressin induces differentiation of stem cells into

cardiomyocytes and promotes heart muscle homeostasis.[11]

It has a very short half-life, between 16 and 24 minutes.[9]

Physiology

Further information: Renal physiology

Function

Vasopressin regulates the

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.[12]

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.[13]

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.[14]

Kidney

Vasopressin has three main effects which are:

  1. 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.,
    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.[16]
  2. Increasing permeability of the inner medullary portion of the collecting duct to
    outer medullary collecting duct
    .
  3. Acute increase of
    collecting duct.[18]

Central nervous system

Vasopressin released within the brain may have several actions:

Regulation

Gene regulation

Further information: AVP gene

Vasopressin is regulated by

BMAL1 in order to reduce Per2 protein levels in the cell.[22] 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.[23]

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.[24]
  • Angiotensin II stimulates AVP secretion, in keeping with its general pressor and pro-volumic effects on the body.[25]
  • Atrial natriuretic peptide inhibits AVP secretion, in part by inhibiting Angiotensin II-induced stimulation of AVP secretion.[25]
  • Cortisol inhibits secretion of antidiuretic hormone.[26]

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, vasopressin secretion is also stimulated in the presence of hypoosmolality (hyponatremia) when the arterial blood volume is low by the unloading of

baroreceptors.[27]

The AVP that is measured in peripheral blood is almost all derived from secretion from the

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).[28]

Vasopressin during surgery and anaesthesia

Vasopressin concentration is used to measure

noxious stimuli,[29][30] predominantly during abdominal surgery,[31][32][33] especially at gut manipulation, traction of viscera,[34][35][36] as well as abdominal insufflation with carbon dioxide during laparoscopic surgery.[37][38]

Receptors

Types of AVP receptors and their actions:

Type Second messenger system Locations Actions Agonists Antagonists
AVPR1A
 Phosphatidylinositol/calcium Liver, kidney, peripheral vasculature, brain Vasoconstriction, glycogen breakdown,[39] platelet aggregation, and release of factor VIII and von Willebrand factor; social recognition,[40] circadian tau[41] Felypressin
AVPR1B or AVPR3
 Phosphatidylinositol/calcium Pituitary gland, brain Adrenocorticotropic hormone secretion in response to stress;[42] social interpretation of olfactory cues[43]
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
endothelial cells[44][45]
 AVP, desmopressin "-vaptan" diuretics, i.e. tolvaptan

Structure and relation to oxytocin

Chemical structure of the arginine vasopressin (argipressin) with an arginine at the 8th amino acid position. Lysine vasopressin differs only in having a lysine in this position.
Chemical structure of oxytocin. Differs from AVP at only the 3rd and 8th position.

The vasopressins are

primary amide.[46] 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.[47]

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.[48][49]

Comparison of vasopressin and oxytocin neuropeptide families:

Vertebrate Vasopressin Family
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
Vertebrate Oxytocin Family
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
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
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
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
†Vasotocin is the evolutionary progenitor of all the vertebrate neurohypophysial hormones.[50]

Medical use

Main article: Vasopressin (medication)

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.[51]

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

vasoconstrictors in certain conditions. Use of vasopressin analogues for esophageal varices commenced in 1970.[52]

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

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.[51]
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

diarrhoea, sweating, paleness, and flatulence. The most severe adverse reactions are myocardial infarction and hypersensitivity.[51]

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.[51]

Interactions

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 article: Syndrome of inappropriate antidiuretic hormone secretion

fluoroquinolones (including ciprofloxacin and moxifloxacin).[9] Finally, it can occur without a clear explanation.[53] Hyponatremia can be treated pharmaceutically through the use of vasopressin receptor antagonists.[53]

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.[54]

Human studies

Vasopressin has shown

autism, major depressive disorder, bipolar disorder, and schizophrenia.[56]

See also

References

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Further reading

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