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|Synonyms||Arginine Vasopressin; Argipressin|
|Source tissues||Supraoptic nucleus; Paraventricular nucleus of hypothalamus|
|Receptors||V1A, V1B, V2, OXTR|
|Metabolism||Predominantly in the liver and kidneys|
|Metabolism||Predominantly in the liver and kidneys|
|Biological half-life||10-20 minutes|
|Chemical and physical data|
|Molar mass||1,084.24 g·mol−1|
|3D model (JSmol)|
|, ADH, ARVP, AVP-NPII, AVRP, VP, arginine vasopressin, Vasopressin|
Vasopressin, also named antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon of that cell, which terminates 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.
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.
It has a very short half-life, between 16–24 minutes.
Vasopressin is available for use as a medication.
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.
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.
Vasopressin has three main effects:
Vasopressin released within the brain may have several actions:
Many factors influence the secretion of vasopressin:
The physiologic 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 is secreted in spite of the presence of hypoosmolality (hyponatremia) when the arterial blood volume is low.
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. However, there are two other sources of AVP with important local effects:
The following describes the actions of AVP:
|Type||Second messenger system||Locations||Actions||Agonists||Antagonists|
|AVPR1A||Phosphatidylinositol/calcium||Liver, kidney, peripheral vasculature, brain||Vasoconstriction, gluconeogenesis, platelet aggregation, and release of factor VIII and von Willebrand factor; social recognition, circadian tau||Felypressin|
|AVPR1B or AVPR3||Phosphatidylinositol/calcium||Pituitary gland, brain||Adrenocorticotropic hormone secretion in response to stress; social interpretation of olfactory cues|
|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||AVP, desmopressin||"-vaptan" diuretics, i.e. tolvaptan|
The vasopressins are peptides consisting of nine amino acids (nonapeptides). (NB: the value in the table above of 164 amino acids is that obtained before the hormone is activated by cleavage.) 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. 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.
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 (see table below). 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.
Below is a table showing the superfamily of vasopressin and oxytocin neuropeptides:
|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|
|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 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|
|Invertebrate VP/OT Superfamily|
|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|
|†Vasotocin is the evolutionary progenitor of all the vertebrate neurohypophysial hormones.|
Vasopressin is used to manage anti-diuretic hormone deficiency. It has off-label uses and is used in the treatment of vasodilatory shock, gastrointestinal bleeding, ventricular tachycardia and ventricular defibrillation. Vasopressin is used to treat diabetes insipidus related to low levels of antiduretic hormone.It is available as Pressyn.
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.
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.
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, diarrhea, nausea, vomiting, sweating, paleness, and flatulence. The most severe adverse reactions are mycardial infarction and hypersensitivy.
The use of vasopressin is contraindicated in the presence of hypersentivity to beef or pork proteins, increased BUN and chronic renal failure. It 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.
There may be a connection between arginine vasopressin and autism.
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).
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 has 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. Hyponatremia can be treated pharmaceutically through the use of vasopressin receptor antagonists.
Vasopressin was elucidated and synthesized for the first time by Vincent du Vigneaud.
Evidence for an effect of AVP on monogamy vs promiscuity 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 promiscuous species in the distribution of AVP receptors, and sometimes in the distribution of vasopressin-containing axons, even when closely related species are compared.