Vasopressin

Arginine vasopressin (AVP), also known as argipressin or antidiuretic hormone (ADH), 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. It has also various functions in the brain.

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

These vasopressins are peptide hormones produced in the hypothalamus. Most of it is stored in the posterior part of the pituitary gland to be released into the blood stream; some of it is also released directly into the brain.

Control
Vasopressin is secreted from the posterior pituitary gland in response to reductions in plasma volume and in response to increases in the plasma osmotic pressure. Secretion in response to reduced plasma volume is activated by pressure receptors in the veins, atria, and arterioles. 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.

Many factors influence the secretion of vasopressin; for instance, ethanol and caffeine reduce vasopressin secretion. The resulting decrease in water reabsorption by the kidneys leads to a higher urine output.

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 neuroendocrine neurons of the paraventricular nucleus into the hypothalamo-hypophysial portal vessels of the median eminence. These vessels carry the peptide directly to the anterior pituitary gland, where it is an important releasing factor for ACTH, acting in conjunction with CRF.
 * Vasopressin is also released into the brain by several different populatons of neurons (see below).

Peripheral actions
Vasopressin acts on three different receptors, termed V1a, V1b and V2. The receptors are differently expressed in different tissues, and exert different actions:
 * V1a - vasoconstriction, gluconeogenesis in the liver, platelet aggregation and release of factor VIII and von Willebrand factor.
 * V1b - corticotropin secretion from the pituitary gland.
 * V2 - control of free water reabsorption in the cortical collecting ducts of the renal medulla. Activation of adenylate cyclase causes a release of aquaporin-2 channels into the luminal membrane of the cells lining the collecting duct. This allows water to be reabsorbed down an osmotic gradient, and so the urine is more concentrated.

Actions within the brain
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.

Structure and relation to oxytocin
The vasopressins are peptides consisting of nine amino acids (nonapeptides). The amino acid sequence of arginine vasopressin is cysteine - tyrosine - phenylalanine - glutamine - asparagine - cysteine - proline - arginine - glycine. The cysteine residues form a sulfur bridge. Lysine vasopressin has a lysine in place of the arginine.

The structure of vasopressin is very similar to that of oxytocin, also a nonapeptide with a sulfur bridge. Vasopressin and oxytocin are both produced by the hypothalamus and are the only known hormones released by the human posterior pituary. The similarity of the two can cause some cross-reactions: oxytocin has a slight antidiuretic function, and high levels of vasopressin can cause uterine contractions.

The magnocellular neurons that make vasopressin are adjacent to magnocellular neurons that make oxytocin, and are similar in many respects.

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

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

Pharmacology
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 extreme cases of bedwetting by children. Terlipressin and related analogues are used as vasocontrictors in certain conditions.

Demeclocycline, a tetracycline antibiotic, is sometimes used to block the action of vasopressin at the kidney in hyponatremia (low blood sodium levels) due to inappropriately high secretion of vasopressin (SIADH, see below), when fluid restriction has failed. A new class of medication (conivaptan, tolvaptan, relcovaptan, lixivaptan) acts by inhibiting the action of vasopressin on its receptors (V1 and V2), with tolvaptan acting on V1a and V2 and the remainder mainly on V1a receptors.

ADH Antidiuretisches Hormon Vazopresino Антидиуретический гормон Hormona antidiurética Vasopressine ADH Antidiuretikus hormon Вазопресин Antidiuretisch hormoon バソプレッシン Hormon antydiuretyczny Hormônio antidiurético