Function<unk>  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<unk> oconstriction. AVP also may have a variety of neurological effects on the brain. It may influence pair-bonding in voles. The high-density distributions of<unk>  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. A very similar substance, lysine<unk>  (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. Kidney<unk>  has three main effects which are: # Increasing the water permeability of distal and cortical collecting tubules (DCT & 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. 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.<unk>  also increases the concentration of calcium in the collecting duct cells, by episodic release from intracellular stores.<unk> , acting through cAMP, also increases transcription of the aquaporin-2 gene, thus increasing the total number of aquaporin-2 molecules in collecting duct cells. # Increasing permeability of the inner medullary portion of the collecting duct to urea by regulating the cell surface expression of urea transporters, 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. Central nervous system<unk>  released within the brain may have several actions: *<unk>  is released into the brain in a circadian rhythm by neurons of the suprachiasmatic nucleus. *<unk>  released from posterior pituitary is associated with nausea. *Recent evidence suggests that<unk>  may have analgesic effects. The analgesia effects of<unk>  were found to be dependent on both stress and sex. Regulation Gene regulation<unk>  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. At the same time, Per2 also inhibits the transcription factors for the AVP gene in order to regulate its expression, the expression of<unk> , and other AVP gene products. Many factors influence the secretion of<unk> : * Ethanol (alcohol) reduces the calcium-dependent secretion of AVP by blocking voltage-gated calcium channels in neurohypophyseal nerve terminals in rats. * Angiotensin II stimulates AVP secretion, in keeping with its general pressor and pro-volumic effects on the body. *Atrial natriuretic peptide inhibits AVP secretion, in part by inhibiting Angiotensin II-induced stimulation of AVP secretion. *Cortisol inhibits secretion of antidiuretic hormone. Production and secretion The physiologic stimulus for secretion of<unk>  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,<unk>  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).<unk>  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).<unk>  during surgery and anaesthesia<unk>  concentration is used to measure surgical stress for evaluation of surgical techniques. Plasma<unk>  concentration is elevated by noxious stimuli, predominantly during abdominal surgery, especially at gut manipulation and traction of viscera. Receptors Types of AVP receptors and their actions: Type Second messenger system Locations Actions Agonists Antagonists AVPR1A Phosphatidylinositol/calcium Liver, kidney, peripheral<unk> culature, brain<unk> oconstriction, 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 Structure and relation to oxytocin Chemical structure of the arginine<unk>  (argipressin) with an arginine at the 8th amino acid position. Lysine<unk>  differs only in having a lysine in this position. Chemical structure of oxytocin. Differs from AVP at only the 3rd and 8th position. The<unk> s are peptides consisting of nine amino acids (nonapeptides). The amino acid sequence of arginine<unk>  (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<unk>  (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<unk>  is found in humans. The structure of oxytocin is very similar to that of the<unk> s: 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<unk>  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. Comparison of<unk>  and oxytocin neuropeptide families: Vertebrate<unk>  Family Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2 Argipressin (AVP,<unk>  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<unk> otocin† 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 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 Invertebrate<unk> /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 †Vasotocin is the evolutionary progenitor of all the vertebrate neurohypophysial hormones.
Vasopressin
Pentostatin
Prorenin
Incretin
Bryostatin
Orexin
Angiotensin II 
Endrin