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14-September-2008 18:02:41 - Vasopressin Arginine vasopressin neurophysin II, antidiuretic hormone, diabetes insipidus, neurohypophyseal Space-filling model of arginine vasopressin Available structures: 1jk4, 1jk6, 1npo, 2bn2 Identifiers Symbols AVP; ADH; AVP-NPII; VP External IDs OMIM: 192340 MGI: 88121 HomoloGene: 417 Gene ontology Molecular function: neurohypophyseal hormone activity Cellular component: extracellular region soluble fraction Biological process: generation of precursor metabolites and energy water transport signal transduction cell-cell signaling diuresis positive regulation of cAMP biosynthetic process vasoconstriction RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 551 11998 Ensembl ENSG00000101200 ENSMUSG00000037727 Uniprot P01185 Q3UUQ5 Refseq NM_000490 mRNA NP_000481 protein NM_009732 mRNA NP_033862 protein Location Chr 20: 3.01 - 3.01 Mb Chr 2: 130.27 - 130.27 Mb Pubmed search 1 2 Arginine vasopressin AVP, also known as vasopressin, argipressin or antidiuretic hormone ADH, is a hormone found in most mammals, including humans.1 Vasopressin is a peptide hormone. It is derived from a preprohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the posterior pituitary. Most of it is stored in the posterior pituitary to be released into the blood stream; some of it is also released directly into the brain. Contents 1 Physiology 1.1 Function 1.1.1 Kidney 1.1.2 Cardiovascular system 1.1.3 Central nervous system CNS 1.2 Control 1.3 Secretion 1.4 Summary Table 2 Structure and relation to oxytocin 3 Role in disease 4 Pharmacology 4.1 Vasopressin analogues 4.2 Vasopressin receptor inhibition 5 References 6 Further reading Physiology Function One of the most important roles of AVP is to regulate the body's retention of water; it is released when the body is dehydrated and causes the kidneys to conserve water, thus concentrating the urine, and reducing urine volume. It also raises blood pressure by inducing moderate vasoconstriction. In addition, it has a variety of neurological effects on the brain, having been found, for example, to influence pair-bonding in voles. A very similar substance, lysine vasopressin LVP or lypressin, has the same function in pigs and is often used in human therapy. Kidney AVP increases the permeability to water of the distal convoluted tubules and collecting tubules in the nephrons of kidneys and thus allows water reabsorption and excretion of a smaller volume of concentrated urine - antidiuresis. This occurs through insertion of additional water channels Aquaporin-2s into the apical membrane of the tubules/collecting duct epithelial cells. The aquaporin allow water to pass out of the nephron at the distal convoluted tubules and the conducting tubules and into the cell, increasing the amount of water re-absorbed from the filtrate. V2 receptors, G protein-coupled receptors coupled to Gs, on the basolateral membrane of the cells lining the distal convoluted tubules and conducting tubules in the nephron have an active site for AVP. The G protein, which is in contact with the V2 receptor inside the cell, move to adenylyl cyclase, triggering adenylyl cyclase to convert ATP into cAMP, plus 2 inorganic phosphates. The cAMP cascade then triggers the insertion of Aquaporin-2 water pores by exocytosis of storage vesicles. The repressor protein that regulates the gene for protein kinase A PKA has a binding site for cAMP, causing the repressor protein to change its shape and leave the operator region of the gene. This allows for transcription of the gene for PKA. PKA then signals ATP to dephosphorylate, providing energy for vesicles which contain aquaporin channel proteins in their membranes to fuse with the apical membrane of the cell. Calcium ions may also be required in this process, therefore it may be possible that, PLC phospholipase C- beta has an associated role. It should be noted that PLC can be activated by a G-protein coupled receptor. AVP also increases permeability of the papillary portion of the collecting duct to urea, allowing increased reabsorption of urea into the medullary interstitium, down the concentration gradient created from the removal of water in the cortical collecting duct. Another renal role for AVP is that it stimulates sodium reabsorption in the thick-ascending loop of Henle. Cardiovascular system Vasopressin increases the resistance of the peripheral vessels and thus increases arterial blood pressure. This effect appears small in healthy individuals; however it becomes an important compensatory mechanism for restoring blood pressure in hypovolemic shock such as occurs during hemorrhage. Central nervous system CNS 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. Control Vasopressin is secreted from the posterior pituitary gland in response to reductions in plasma volume, in response to increases in the plasma osmolality, and in response to Cholecystokinin by the small intestine: 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. Secretion in response to increases in plasma Cholecystokinin is mediated by an unknown pathway. 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 alcohol reduces vasopressin secretion. The resulting decrease in water reabsorption by the kidneys leads to a higher urine output. Angiotensin II may stimulate the secretion of vasopressin.2 Secretion The main stimulus for secretion of vasopressin is increased osmolality of plasma. Reduced volume of extracellular fluid also has this effect, but is a less sensitive mechanism. 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 produced in the supraoptic nucleus of the hypothalamus and travels down the axons in neurosecretory granules through the infundibulum. These carry the peptide directly to the posterior pituitary gland, where it is stored in Herring bodies until it is released into the blood. Vasopressin is also released into the brain by several different populations of neurons see below. Summary Table Here is a table summarizing some of the actions of AVP at its 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,3 circadian tau4 AVPR1B phosphatidylinositol/calcium pituitary gland, brain adrenocorticotropic hormone secretion in response to stress;5 social interpretation of olfactory cues6 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 cells78 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 arginine vasopressin is Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly, with the cysteine residues forming 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. 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 vasopressin 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 vasopressin 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, 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 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. Vasotocin is only found in hagfish lampreys.9 Role in disease Decreased vasopressin release or decreased renal sensitivity to vasopressin leads to diabetes insipidus, a condition featuring hypernatremia increased blood sodium concentration, polyuria excess urine production, and polydipsia thirst. High levels of vasopressin secretion syndrome of inappropriate antidiuretic hormone, SIADH and resultant hyponatremia low blood sodium levels occurs in brain diseases and conditions of the lungs Small cell lung carcinoma. 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 vasopressin secretion. This may cause mild hyponatremia for several days. Pharmacology Vasopressin analogues 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. Use of vasopressin analogues for esophageal varices commenced in 1970.10 Vasopressin 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 norepinephrine. It had been shown to be more effective than epinephrine in asystolic cardiac arrest.11 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 vasopressin in this situation, but these studies relied on sub-group analysis and better designed prospective studies show no benefit in ACLS.1213 Vasopressin receptor inhibition Demeclocycline, a tetracycline antibiotic, is sometimes used to block the action of vasopressin in the kidney in hyponatremia due to inappropriately high secretion of vasopressin SIADH, see above, 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 conivaptan acting on V1a and V2 and the remainder mainly on V2 receptors. The same class of drugs is also being studied in congestive heart failure. References ^ Caldwell HK, Young WS III 2006. Oxytocin and Vasopressin: Genetics and Behavioral Implications, in Lajtha A, Lim R: Handbook of Neurochemistry and Molecular Neurobiology: Neuroactive Proteins and Peptides, 3rd ion, Berlin: Springer, pages 573-607. ISBN 0-387-30348-0. ^ Vander, Arthur J. 1995. Renal physiology, 5th ion, New York: McGraw-Hill, Health Professions Division. ISBN 0-07-067009-9. ^ Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ Mar 2004. Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology 29 3: 483-93. doi:10.1038/sj.npp.1300360. PMID 14647484. ^ Wersinger SR, Caldwell HK, Martinez L, Gold P, Hu SB, Young WS Aug 2007. Vasopressin 1a receptor knockout mice have a subtle olfactory deficit but normal aggression. Genes Brain Behav. 6 6: 540-51. doi:10.1111/j.1601-183X.2006.00281.x. PMID 17083331. ^ Lolait SJ, Stewart LQ, Jessop DS, Young WS, O'Carroll AM Feb 2007. The hypothalamic-pituitary-adrenal axis response to stress in mice lacking functional vasopressin V1b receptors. Endocrinology 148 2: 849-56. doi:10.1210/en.2006-1309. PMID 17122081. ^ Wersinger SR, Kelliher KR, Zufall F, Lolait SJ, O'Carroll AM, Young WS Dec 2004. Social motivation is reduced in vasopressin 1b receptor null mice despite normal performance in an olfactory discrimination task. Horm Behav 46 5: 638-45. doi:10.1016/j.yhbeh.2004.07.004. PMID 15555506. ^ Kanwar S, Woodman RC, Poon MC, Murohara T, Lefer AM, Davenpeck KL, Kubes P Oct 1995. Desmopressin induces endothelial P-selectin expression and leukocyte rolling in postcapillary venules. Blood 86 7: 2760-6. PMID 7545469. ^ Kaufmann JE, Oksche A, Wollheim CB, Günther G, Rosenthal W, Vischer UM Jul 2000. Vasopressin-induced von Willebrand factor secretion from endothelial cells involves V2 receptors and cAMP. J. Clin. Invest. 106 1: 107-16. doi:10.1172/JCI9516. PMID 10880054. ^ Acher R, Chauvet J Jul 1995. The neurohypophysial endocrine regulatory cascade: precursors, mediators, receptors, and effectors. Front Neuroendocrinol 16 3: 237-89. doi:10.1006/frne.1995.1009. PMID 7556852. ^ Baum S, Nusbaum M, Tumen HJ 1970. The control of gastrointestinal hemorrhage by selective mesenteric infusion of pitressin. Gastroenterology 58: 926. ^ Wenzel V, Krismer AC, Arntz HR, Sitter H, Stadlbauer KH, Lindner KH Jan 2004. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N. Engl. J. Med. 350 2: 105-13. doi:10.1056/NEJMoa025431. PMID 14711909. ^ Grmec S, Mally S Feb 2006. Vasopressin improves outcome in out-of-hospital cardiopulmonary resuscitation of ventricular fibrillation and pulseless ventricular tachycardia: a observational cohort study. Crit Care 10 1: R13. doi:10.1186/cc3967. PMID 16420660. ^ Gueugniaud PY, David JS, Chanzy E, et al Jul 2008. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N. Engl. J. Med. 359 1: 21-30. doi:10.1056/NEJMoa0706873. PMID 18596271. Further reading Rector, Floyd C.; Brenner, Barry M. 2004. Brenner Rector's the kidney, 7th ion, Philadelphia: Saunders. ISBN 0-7216-0164-2. v d e Endocrine system: hormones/endocrine glands Peptide hormones, Steroid hormones Hypothalamic-pituitary Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α FSH, LH, TSH, GH, prolactin, POMC ACTH, MSH, endorphins, lipotropin Adrenal axis Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA Thyroid axis Thyroid: thyroid hormone T3 and T4 - calcitonin - Parathyroid: PTH Gonadal axis Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin pregnancy Other end. glands Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin Non-end. glands Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Thymulin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor IGF-1, IGF-2 Target-derived NGF, BDNF, NT-3 v d e Urinary system, physiology: renal physiology and acid base physiology Filtration Renal blood flow - Ultrafiltration - Countercurrent exchange Hormones affecting filtration Antidiuretic hormone ADH - Aldosterone - Atrial natriuretic peptide Secretion/clearance Pharmacokinetics - Clearance of medications Reabsorption Solvent drag - Na+ - Cl- - urea - glucose - oligopeptides - protein Endocrine Renin - Erythropoietin EPO - Calcitriol Active vitamin D - Prostaglandins Assessing Renal function/ Measures of dialysis Glomerular filtration rate - Creatinine clearance - Renal clearance ratio - Urea reduction ratio - Kt/V - Standardized Kt/V - Hemodialysis product - PAH clearance Effective renal plasma flow - Extraction ratio Acid base physiology Fluid balance - Darrow Yannet diagram - Body water - Interstitial fluid - Extracellular fluid - Intracellular fluid/Cytosol - Plasma - Transcellular fluid - Base excess - Davenport diagram - Anion gap - Arterial blood gas Buffering/compensation Bicarbonate buffering system - Respiratory compensation - Renal compensation v d e Peptides: neuropeptides Hypothalamic Somatostatin - CRH - GnRH - GHRH - Orexins - TRH - POMC ACTH, MSH, Lipotropin Gastrointestinal hormones Cholecystokinin - Gastric inhibitory polypeptide - Gastrin - Motilin - Secretin - Vasoactive intestinal peptide Other hormones Vasopressin - Calcitonin - Other Angiotensin - Bombesin/Neuromedin B - Calcitonin gene-related peptide - Carnosine - Delta sleep-inducing peptide - FMRFamide - Galanin - Gastrin releasing peptide - Kinins Bradykinin, Tachykinins - Neuromedin B, N, U - Neuropeptide Y - Neurophysins - Neurotensin - Opioid peptide - Pancreatic polypeptide - Pituitary adenylate cyclase activating peptide Retrieved from http://en..org/wiki/Vasopressin Categories: Genes on chromosome 20 | Human proteins | Neuroscience | Neurotransmitters | Neuropeptides | Nootropics | Posterior pituitary hormones | Neuroendocrinology | Renal physiology Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages العربية БългарÑ?ки ÄŒesky Dansk Deutsch Þ‹Þ¨ÞˆÞ¬Þ€Þ¨Þ„Þ¦Þ?Þ° Español Esperanto Français Galego í•œêµì–´ Hrvatski Bahasa Indonesia Italiano עברית Lietuvių Magyar МакедонÑ?ки Nederlands 日本語 ‪Norsk bokmÃ¥l‬ Polski Português РуÑ?Ñ?кий Shqip SlovenÄ?ina Suomi Svenska ä¸æ–‡ This page was last modified on 10 September 2008, at 23:00
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