Vasopressin

Arginine vasopressin (antidiuretic hormone) -human
Identifiers
Symbol(s)	AVP VP, ADH
Entrez	551
OMIM	192340
RefSeq	NM_000490
UniProt	P01185
Other data
Locus	Chr. 20 p13

Arginine vasopressin receptor 1a -human
Identifiers
Symbol(s)	AVPR1A
Entrez	552
OMIM	600821
RefSeq	NM_000706
UniProt	P37288
Other data
Locus	Chr. 12 q14-15

Arginine vasopressin receptor 1b -human
Identifiers
Symbol(s)	AVPR1B
Entrez	553
OMIM	600264
RefSeq	NM_000707
UniProt	P47901
Other data
Locus	Chr. 1 q32

Arginine vasopressin receptor 2 -human
Identifiers
Symbol(s)	AVPR2
Entrez	554
OMIM	304800
RefSeq	NM_000054
UniProt	P30518
Other data
Locus	Chr. X q28

Arginine vasopressin (AVP), also known as antidiuretic hormone (ADH) or argipressin, is a human hormone that is mainly released when the body is low on water; it causes the kidneys to conserve water by concentrating the urine and reducing urine volume. It also has various functions in the brain and blood vessels.

A very similar substance, lysine vasopressin (LVP) or lypressin, has the same function in pigs and is often used in human therapy.

Vasopressin is a peptide hormone liberated from a preprohormone precursor], the bulk of which is synthesized by the magnocelluollar neurons of the paraventricular and supraoptic nuclei of the hypothalamus, as it is transported to the posterior part of the pituitary gland to be released into the blood stream. Some of it is also released directly into the brain from the dendrites of the paraventricular and suproptic neurons as well as from other brain neurons (see below).

Physiology

Control

Vasopressin is secreted from the posterior pituitary gland in response to reductions in plasma volume and in response to increases in the plasma osmolality:

• Secretion in response to reduced plasma volume is activated by pressure receptors in the veins, atria, and carotids.
• Secretion in response to increases in plasma osmotic pressure is mediated by osmoreceptors in the hypothalamus.

The neurons that make vasopressin, in the supraoptic nucleus and paraventricular nucleus, are themselves osmoreceptors, but they also receive synaptic input from other osmoreceptors located in regions adjacent to the anterior wall of the third ventricle. These regions include the organum vasculosum of the lamina terminalis and the subfornical organ.

Many factors influence the secretion of vasopressin:

• Ethanol and caffeine reduce vasopressin secretion. The resulting decrease in water reabsorption by the kidneys leads to a higher urine output. Coffee is an example of a food product that supresses the body's release of antidiuretic hormones, due to its level of caffeine. This intake of caffeine causes the body to lose more water and may lead to dehydration if consumed excessively.
• Angiotensin II stimulates the secretion of vasopressin.

Sources

The vasopressin that is measured in peripheral blood is almost all derived from secretion from the posterior pituitary gland (except in cases of vasopressin-secreting tumours). However there are two other sources of vasopressin with important local effects:

• Vasopressin is secreted from parvocellular neurons of the paraventricular nucleus at the median eminence into the short portal vessels of the pituitary stalk. These vessels carry the peptide directly to the anterior pituitary gland, where it is an important releasing factor for ACTH, acting in conjunction with CRH.
• Vasopressin is also released into the brain by several different populations of neurons (see below).

Central actions

Vasopressin released within the brain has many actions:

• It has been implicated in memory formation, including delayed reflexes, image, short- and long-term memory, though the mechanism remains unknown, and these findings are controversial. However, the synthetic vasopressin analogue desmopressin has come to interest as a likely nootropic.

• Vasopressin is released into the brain in a circadian rhythm by neurons of the suprachiasmatic nucleus of the hypothalamus.

• Vasopressin released from centrally-projecting hypothalamic neurons is involved in aggression, blood pressure regulation and temperature regulation.

In recent years there has been particular interest in the role of vasopressin in social behavior. It is thought that vasopressin, released into the brain during sexual activity, initiates and sustains patterns of activity that support the pair-bond between the sexual partners; in particular, vasopressin seems to induce the male to become aggressive towards other males.

Evidence for this 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 vasopressin receptors, and sometimes in the distribution of vasopressin-containing axons, even when closely-related species are compared. Moreover, studies involving either injecting vasopressin agonists into the brain, or blocking the actions of vasopressin, support the hypothesis that vasopressin is involved in aggression towards other males. There is also evidence that differences in the vasopressin receptor gene between individual members of a species might be predictive of differences in social behavior.

Summary Table

Here is a table summarizing some of the actions of Avp at it's three receptors, differently expressed in different tissues and exerting different actions:

Type	Second messenger system	Locations	Actions
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
AVPR1B	phosphatidylinositol/calcium	pituitary gland, brain	adrenocorticotropic hormone secretion in response to stress; social interpretation to olfactory cues
AVPR2	adenylate cyclase/cAMP	apical 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.

Structure and relation to oxytocin

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 AVP is Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly, with the cysteine residues form a sulfur bridge. Lysine vasopressin has a lysine in place of the arginine.

The structure of oxytocin is very similar to that of the vasopressins: it is also a nonapeptide with a sulfur bridge and its amino acid sequence differs at only two positions (see table below). These two neuropeptides are encoded by genes that arose through duplication approximately 400 million years ago. The two genes are located on the same chromosome separated by a relatively small distance of less than 15,000 bases in various species. The magnocellular neurons that make AVP are adjacent to magnocellular neurons that make 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.

Here 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
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-Ile-Gly-NH2	Mesotocin	Most marsupials, all birds, reptiles, amphibians, lungfishes
Cys-Tyr-Ile-Ser-Asn-Cys-Pro-Ile-Gly-NH2	Isotocin	Bony fishes
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	Diuretic Hormone	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
†Vasotocin is the evolutionary progenitor of all the vertebrate neurohypophysial hormones. Only vasotocin found in hagfish & lampreys (Agnatha appeared 500 million years ago)

Role in disease

Decreased AVP release or decreased renal sensitivity to AVP leads to diabetes insipidus, a condition featuring hypernatremia (increased blood sodium content), polyuria (excess urine production), and polydipsia (thirst).

High levels of AVP secretion (syndrome of inappropriate antidiuretic hormone, SIADH) and resultant hyponatremia (low blood sodium levels) occurs in brain diseases and conditions of the lungs. In the perioperative period, the effects of surgical stress and some commonly used medications (e.g., opiates, syntocinon, anti-emetics) lead to a similar state of excess AVP secretion. This may cause mild hyponatraemia for several days.

Pharmacology

Vasopressin analogues

AVP agonists are used therapeutically in various conditions, and its long-acting synthetic analogue desmopressin is used in conditions featuring low AVP secretion, as well as for control of bleeding (in some forms of von Willebrand disease) and in extreme cases of bedwetting by children. Terlipressin and related analogues are used as vasocontrictors in certain conditions. Use of AVP analogues for esophageal varices commenced in 1970.

AVP infusion has been used as a second line of management in septic shock patients not responding to high dose of inotropes (e.g., dopamine or epinephrine). It had been shown to be more effective than epinephrine in asystolic cardiac arrest. While not all studies are in agreement, a 2006 study of out-of hospital cardiac arrests has added to the evidence for the superiority of AVP in this situation.

Vasopressin receptor inhibition

Demeclocycline, a tetracycline antibiotic, is sometimes used to block the action of AVP in the kidney in hyponatremia due to inappropriately high secretion of AVP (SIADH, see above), when fluid restriction has failed. A new class of medication (conivaptan, tolvaptan, relcovaptan, lixivaptan) acts by inhibiting the action of AVP on its receptors (V1 and V2), with tolvaptan acting on V1a and V2 and the remainder mainly on V1a receptors. The same class of drugs is also being studied in congestive heart failure.

Further reading

• Brenner & Rector's The Kidney, 7th ed., Saunders, 2004. Full Text with MDConsult subscription

• Caldwell, H.K. and Young, W.S., III. Oxytocin and Vasopressin: Genetics and Behavioral Implications in Lim, R. (ed.) Handbook of Neurochemistry and Molecular Neurobiology, 3rd edition, Springer, New York, pp. 573-607, 2006. 320kb PDF