Serotonin 28764 224931574 2008-07-11T01:43:54Z 24.189.153.85 /* External links */ {{for|the professional [[stable (wrestling)|wrestling stable]]|Raven's Nest#Serotonin}} {{Chembox new | ImageFileL1 = Serotonin (5-HT).svg | ImageSizeL1 = 145px | ImageFileR1 = Serotonin-3D-vdW.png | ImageSizeR1 = 145px | IUPACName = 5-Hydroxytryptamine or<br>3-(2-aminoethyl)-1''H''-indol-5-ol | OtherNames = | Section1 = {{Chembox Identifiers | CASNo = 50-67-9 | PubChem = 5202 | SMILES = NCCc1c[nH]c2ccc(O)cc12 | MeSHName = Serotonin | InChI = <small>1/C10H12N2O/c11-4-3-7-6-12-10-2-1- 8(13)5-9(7)10/h1-2,5-6,12-13H,3-4,11H2</small> }} | Section2 = {{Chembox Properties | Formula = </sub>C<sub>10</sub>H<sub>12</sub>N<sub>2</sub>O<sub> | MolarMass = 176.215 | Appearance = | Density = | MeltingPt = | BoilingPt = }} | Section3 = {{Chembox Hazards | Solubility = | MainHazards = | FlashPt = | Autoignition = }} }} '''Serotonin''' ({{pronEng|ˌsɛrəˈtoʊnən}}) ('''5-hydroxytryptamine''', or '''5-HT''') is a [[monoamine]] [[neurotransmitter]] synthesized in serotonergic [[neuron]]s in the [[central nervous system]] (CNS) and [[enterochromaffin cell]]s in the [[gastrointestinal tract]] of [[animals]] including [[humans]]. Serotonin is also found in many [[mushrooms]] and [[plant]]s, including [[fruit]]s and [[vegetable]]s. == Function == In the [[central nervous system]], serotonin plays an important role as a [[neurotransmitter]] in the modulation of [[anger]], [[aggression]], [[Thermoregulation|body temperature]], [[Mood (psychology)|mood]], [[sleep]], [[Human sexual behavior|sexuality]], [[appetite]], and [[metabolism]], as well as stimulating [[vomiting]].{{Fact|date=June 2008}} Serotonin has broad activities in the brain, and genetic variation in serotonin receptors and the [[serotonin transporter]], which facilitates reuptake of serotonin into presynapses, have been implicated in neurological diseases. Drugs targeting serotonin-induced pathways are being used in the treatment of many psychiatric disorders, and one focus of clinical research is the influence of genetics on serotonin action and metabolism in psychiatric settings. Such studies have revealed that the variation in the promoter region of the serotonin transporter protein accounts for nearly 10% of total variance in anxiety-related personality <ref> {{Cite journal | author = Lesch, K.; Bengel, D.; Heils, A.; Sabol, S.Z.; Greenberg, B.D.; Petri, S.; andClemens R Müller, J.B.; Hamer, D.H. & Murphy, D.L. | title = Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region | journal = [[Science]] | year = 1996 | volume = 274 | pages = 1527–31 | doi = 10.1126/science.274.5292.1527 | pmid = 8929413}}</ref>, and the effect of this gene on [[Major depressive disorder|depression]] was found to interact with the environment <ref>{{Cite journal | author = Caspi, A.; Sugden, K.; Moffitt, T.E.; Taylor, A.; Craig, I.W.; Harrington, W.; McClay, J.; Mill, J.; Martin, J.; Braithwaite, A. & Poulton, R. | title = Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene | journal = [[Science]] | year = 2003 | volume = 301 | pages = 386–89 | doi = 10.1126/science.1083968 | pmid = 12869766}}</ref>. Levels of serotonin in the brain show association with aggression (Caspi et al. 2002), and a mutation in the gene which codes for the [[5-HT2A receptor|5-HT<sub>2A</sub>]] receptor may double the risk of suicide for those with that genotype.<ref>{{Cite journal | author = [[Greg Basky]] | title = Suicide linked to serotonin gene | journal = [[CMAJ]] | month = May | year = 2000 | volume = 162 | issue = 9 | url = http://www.cmaj.ca/cgi/content/full/162/9/1343-a }}</ref> Using the [[ultimatum game]] as model, it was shown that people whose serotonin levels have been artificially lowered will reject unfair offers more often than players with normal serotonin levels.<ref>{{Cite journal | doi = 10.1126/science.1155577 | pages = 1155577 | last = Crockett | first = Molly J. | coauthors = Luke Clark, Golnaz Tabibnia, Matthew D. Lieberman, Trevor W. Robbins | title = Serotonin Modulates Behavioral Reactions to Unfairness | journal = Science | accessdate = 2008-06-22 | date = 2008-06-05 | url = http://www.scn.ucla.edu/pdf/Crockett%20(2008).pdf | pmid = 18535210 }}</ref> In addition, serotonin is also a [[Periphery|peripheral]] signal mediator. It is found extensively in the human [[gastrointestinal tract]] as about 80-90% of the body's total serotonin is found in the enterochromaffin cells in the gut.<ref>[http://web.indstate.edu/thcme/mwking/nerves.html Indiana State University]</ref><ref>[http://www.clinlabnavigator.com/Tests/Serotonin.html] Serotonin tests info, Accessed May 6, 2008</ref> In the blood, the major storage site is [[platelet]]s, which collect serotonin for use in mediating post-injury vasoconstriction. {{Fact|date=June 2008}} Recent research suggests that serotonin plays an important role in [[liver]] regeneration and acts as a [[mitogen]] (induces cell division) throughout the body. <b>Serotonin and SIDS</b> <P> Defective signalling of serotonin in the brain may be at the root cause of sudden infant death syndrome (SIDS), Italian researchers have found. <P>Scientists from the European Molecular Biology Laboratory in Monterotondo, Italy genetically modified the lab mice to produce low levels of the brain signaling protein serotonin. The results showed the mice suffered drops in heart rate and other symptoms of SIDS, and many of the animals died at an early age. <P>Researchers now believe that low levels of serotonin in the animals' brainstems, which control heartbeat and breathing, may have caused sudden death, researchers said in the July 4, 2008 issue of Science. <ref>{{cite journal | author = Lesurtel M. et al | year = 2006 | title = Platelet-derived serotonin mediates liver regeneration | journal = [[Science (journal)|Science]] | volume = 312 | issue = 5770 | pages = 104–7 | pmid = 16601191 | doi = 10.1126/science.1123842 }}</ref> ==Anatomy== === Gross anatomy === The neurons of the [[raphe nuclei]] are the principal source of 5-HT release in the brain.<ref>{{cite book | author = [[Alan Frazer]] and [[Julie G. Hensler]] | editor = [[George J. Siegel]] | others = Bernard W. Agranoff, Stephen K. Fisher, R. Wayne Albers, Michael D. Uhler | title = Basic Neurochemistry | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm | edition = Sixth | year = 1999 | publisher = Lippincott Williams and Wilkins | id = ISBN 0-397-51820-X | chapter = Understanding the neuroanatomical organization of serotonergic cells in the brain provides insight into the functions of this neurotransmitter | chapterurl = http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=raphe+AND+serotonin+release+AND+bnchm%5Bbook%5D+AND+160428%5Buid%5D&rid=bnchm.section.946#949 | quote = In 1964, Dahlstrom and Fuxe (discussed in [2]), using the Falck-Hillarp technique of histofluorescence, observed that the majority of serotonergic soma are found in cell body groups, which previously had been designated as the raphe nuclei. }}</ref> The raphe nuclei are neurons grouped into about nine pairs and distributed along the entire length of the [[brainstem]], centered around the [[reticular formation]].<ref>|The [[Raphe nuclei]] group of [[neurons]] are located along the [[reticular formation|brain stem]] from the labels '[[mesencephalon|Mid Brain]]' to '[[medulla oblongata|Oblongata]]', centered on the [[pons]]. ([[:Image:Gray715.png|See relevant image]].)</ref> Axons from the neurons of the raphe nuclei form a [[neurotransmitter system]], reaching large areas of the brain. Axons of neurons in the ''caudal'' [[dorsal raphe nucleus]] terminate in the following locations: * [[Deep cerebellar nuclei]] * [[Cerebellar cortex]] * [[Spinal cord]] On the other hand, axons of neurons in the ''rostral'' [[dorsal raphe nucleus]] terminate in e.g.: <div style="column-count: 3;"> * [[Thalamus]] * [[Striatum]] * [[Hypothalamus]] * [[Nucleus accumbens]] * [[Neocortex]] * [[Cingulate gyrus]] * [[Cingulum]] * [[Hippocampus]] * [[Amygdala]]</div> Thus, activation of this serotonin system has effects on large areas of the brain. === Microanatomy === Serotonin is released from serotonergic varicosities (swellings) into the extra neuronal space, but not from synaptic terminal [[bouton]]s as other neurotransmitters. {{Fact|date=June 2008}} Serotonin diffuses over a relatively wide gap (>20µm) to activate [[5-HT receptor]]s located on the [[dendrite]]s, cell bodies and [[presynaptic terminal]]s of adjacent neurons. ==== Receptors ==== {{main|5-HT receptor}} [[5-HT receptor]]s are the [[receptor (biochemistry)|receptors]] for serotonin. They are located on the cell membrane of [[Neuron|nerve cells]] and other cell types in animals and mediate the effects of serotonin as the [[endogenous]] [[ligand]] and of a broad range of pharmaceutical and [[Psychedelics, dissociatives and deliriants|hallucinogenic drugs]]. With the exception of the [[5-HT3|5-HT<sub>3</sub> receptor]], a ligand gated [[ion channel]], all other 5-HT receptors are [[G-protein-coupled receptor|G protein coupled seven transmembrane]] (or ''heptahelical'') receptors that activate an [[intracellular]] [[second messenger]] cascade. {{Fact|date=June 2008}} ==== Termination ==== Serotonergic action is terminated primarily via [[reuptake|uptake]] of 5-HT from the synapse. This is through the specific [[monoamine transporter]] for 5-HT, [[Serotonin transporter|5-HT reuptake transporter]], on the presynaptic neuron. Various agents can inhibit 5-HT reuptake including [[MDMA]] (ecstasy), [[amphetamine]], [[cocaine]], [[dextromethorphan]] (an [[antitussive]]), [[tricyclic antidepressants]] (TCAs) and [[selective serotonin reuptake inhibitor]]s (SSRIs). ===Endothelial cell function and Serotonin === 5-hydroxytryptamine evokes [[endothelium|endothelial]] [[nitric oxide synthase]] activation and stimulates phosphorylation of p44/p42 mitogen-activated protein kinase activation in bovine aortic endothelial cell cultures.<ref>{{Cite journal | author = [[JE McDuffie]] | title = -hydroxytryptamine stimulates phosphorylation of p44/p42 mitogen-activated protein kinase activation in bovine aortic endothelial cell cultures. | journal = [[J Cardiovasc Pharmacol]] | month = Mar | year = 2000 | volume = 35 | issue = 3 | url = http://www.cardiovascularpharm.com/pt/re/jcardiopharm/abstract.00005344-200003000-00008.htm;jsessionid=LLhXJN6PTXBlSKWpG3mTNChLl7C4wQZFQF2yyFWnlQLcdph7zkQq!-1990489359!181195628!8091!-1}}</ref> == Synthesis == [[Image:Serotonin biosynthesis.svg|thumb|right|400px|The pathway for the synthesis of serotonin from tryptophan]] In the body, serotonin is synthesized from the [[amino acid]] [[tryptophan]] by a short [[metabolic pathway]] consisting of two [[enzyme]]s: [[tryptophan hydroxylase]] (TPH) and [[Aromatic L-amino acid decarboxylase|amino acid decarboxylase]] (DDC). The TPH-mediated reaction is the rate-limiting step in the pathway. TPH has been shown to exist in two forms: TPH1, found in several [[Biological tissue|tissues]], and TPH2, which is a brain-specific [[Protein isoform|isoform]]. There is evidence that [[polymorphism (biology)|genetic polymorphisms]] in both these subtypes influence susceptibility to anxiety and depression. There is also evidence that [[ovarian hormones]] can affect the expression of TPH in various species, suggesting a possible mechanism for [[postpartum depression]] and [[premenstrual stress syndrome]]. Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system because it does not cross the [[blood-brain barrier]]. However, [[tryptophan]] and its [[metabolite]] [[5-hydroxytryptophan]] (5-HTP), from which serotonin is synthesized, can and do cross the blood-brain barrier. These agents are available as [[dietary supplement]]s and may be effective serotonergic agents. One product of serotonin breakdown is [[5-Hydroxyindoleacetic acid]] (5 HIAA), which is excreted in the [[urine]]. Serotonin and 5 HIAA are sometimes produced in excess amounts by certain [[tumor]]s or [[cancer]]s, and levels of these substances may be measured in the urine to test for these tumors. == Drugs targeting the 5-HT system == Several classes of [[drugs]] target the 5-HT system including some [[antidepressant]]s, [[antipsychotic]]s, [[anxiolytic]]s, [[antiemetic]]s, and [[migraine|antimigraine drugs]] as well as the [[psychedelic drug]]s and [[empathogen]]s. === Psychoactive drugs === The [[psychedelic drug]]s [[psilocin]]/[[psilocybin]], [[dimethyltryptamine|DMT]], [[mescaline]], and [[LSD]] mimic the action of serotonin primarily at [[5-HT2A receptor|5-HT<sub>2A</sub> receptor]]. The [[empathogen]] [[MDMA]] (ecstasy) releases serotonin from synaptic vesicles of neurons. === Antidepressants === The [[MAOI]]s prevent the breakdown of [[monoamine neurotransmitter]]s (including serotonin), and therefore increase concentrations of the neurotransmitter in the brain. MAOI therapy is associated with many adverse drug reactions, and patients are at risk of [[hypertensive emergency]] triggered by foods with high [[tyramine]] content and certain drugs. Some drugs inhibit the re-uptake of serotonin, making it stay in the synapse longer. The [[tricyclic antidepressants]] (TCAs) inhibit the re-uptake of both serotonin and [[norepinephrine]]. The newer [[Selective and non-selective|selective]] serotonin re-uptake inhibitors ([[SSRI]]s) have fewer (though still numerous) side-effects and fewer interactions with other drugs. === Antiemetics === [[5-HT3 antagonist|5-HT<sub>3</sub> antagonist]]s such as [[ondansetron]], [[granisetron]], and [[tropisetron]] are important [[antiemetic]] agents. They are particularly important in treating the [[nausea]] and [[vomiting]] that occur during anticancer [[chemotherapy]] using cytotoxic drugs. Another application is in treatment of post-operative nausea and vomiting. Applications to the treatment of depression and other mental and psychological conditions have also been investigated with some positive results. == Pathology == If neurons that make serotonin — serotonergic neurons — are abnormal in infants, there is a risk of [[sudden infant death syndrome]] (SIDS).<ref name="SIDS">{{cite journal | author = Paterson D.S. et al | year = 2006 | title = Multiple Serotonergic Brainstem Abnormalities in Sudden Infant Death Syndrome | journal = Journal of the American Medical Association | volume = 296 | number = 17 | pages = 2124–2132 | doi = 10.1001/jama.296.17.2124 <!--Retrieved from CrossRef by DOI bot--> }}</ref><ref>[http://www.sciencedaily.com/releases/2007/03/070309103136.htm Sciencedaily Report ''Anger and Aggression in Women: Blame It On Genetics'']</ref> Low levels of serotonin may also be associated with [[Relationship between religion and science#Scientific study of religion|intense religious experiences]].<ref>Lars Farde & Jacqueline Borg, section of psychiatry at Karolinska Institutet in Stockholm, Sweden 2003, [http://ajp.psychiatryonline.org/cgi/content/full/160/11/1965? the study] and a [http://www.beliefnet.com/story/140/story_14076_1.html vulgarized article]</ref> Recent research conducted at [[Rockefeller University]] shows that in both patients who suffer from depression and in mice that model the disorder, levels of the [[p11 protein]] are decreased. This protein is related to serotonin transmission within the brain.<ref>{{cite journal | author = Svenningsson P, et al | year = 2006 | title = Alterations in 5-HT1B receptor function by p11 in depression-like states | journal = Science | volume = 311 | issue = 5757 | pages = 77–80 | pmid = 16400147 | doi = 10.1126/science.1117571 <!--Retrieved from CrossRef by DOI bot--> }}</ref> [[Obsessive-compulsive disorder]] (OCD) can be a debilitating disorder with the following two anxiety-related essential features: obsessions (undesirable, recurrent, disturbing thoughts) and compulsions (repetitive or ritualized behaviors). Some research shows that it may have to do with serotonin, which helps to keep people from repeating the same behaviors over and over again. A person who has OCD may not have enough serotonin. Therefore, many people who have OCD can function better when they take medicines that increase the amount of serotonin in their brain. === Serotonin syndrome === Extremely high levels of serotonin can have toxic and potentially fatal effects, causing a condition known as [[serotonin syndrome]]. In practice, such toxic levels are essentially impossible to reach through an [[overdose]] of a single anti-depressant drug, but require a combination of serotonergic agents, such as an [[SSRI]] with an [[MAOI]].<ref>Isbister, G.K., et al., Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. Journal of Toxicology. Clinical Toxicology, 2004. 42(3): p. 277-85.</ref> The intensity of the symptoms of serotonin syndrome vary over a wide spectrum, and the milder forms are seen even at non-toxic levels.<ref>Dunkley, E.J.C., et al., Hunter Serotonin Toxicity Criteria: a simple and accurate diagnostic decision rule for serotonin toxicity. Quarterly Journal of Medicine, 2003. 96: p. 635-642.</ref> For example, recreational doses of [[MDMA]] (ecstasy) will generally cause such symptoms but only rarely lead to true [[toxicity]].{{Fact|date=February 2008}} === Chronic diseases resulting from serotonin 5-HT<sub>2B</sub> overstimulation === {{main|Cardiac fibrosis}} In blood, serotonin stored in platelets is active wherever platelets bind, as a vasoconstrictor to stop bleeding, and also as a fibrocyte mitotic, to aid healing. Because of these effects, overdoses of serotonin, or serotonin agonist drugs, may cause acute or chronic pulmonary hypertension from pulmonary vasoconstriction, or else syndromes of [[retroperitoneal fibrosis]] or cardiac valve fibrosis ([[endocardial fibrosis]]) from overstimulation of serotonic growth receptors on fibrocytes.{{Fact|date=April 2008}} Serotonin itself may cause a syndrome of cardiac fibrosis when it is eaten in large quantities in the diet (the Matoki banana of East Africa) or when it is over-secreted by certain mid-gut [[carcinoid]] tumors.{{Fact|date=April 2008}} The valvular fibrosis in such cases is typically on the right side of the heart, since excess serotonin in the serum outside platelets is metabolized in the lungs, and does not reach the left circulation.{{Fact|date=April 2008}} Serotonergic [[agonist]] drugs in overdose in experimental animals not only cause acute (and sometimes fatal) [[pulmonary hypertension]], but there is epidemiologic evidence that chronic use of certain of these drugs produce a chronic pulmonary hypertensive syndrome in humans.{{Fact|date=April 2008}} Some serotinergic agonist drugs also cause fibrosis anywhere in the body, particularly the syndrome of [[retroperitoneal fibrosis]], as well as [[cardiac fibrosis|cardiac valve fibrosis]].<ref>[http://books.google.com/books?id=AW7M6jBixj4C&pg=PA626&lpg=PA626&dq=ergotamine+endocardial+fibrosis&source=web&ots=BrjNzsIc-N&sig=X-WM0TaoW6I5nkx6xiTsxJYvLHo. books.google.com] Accessed May 6, 2008</ref> In the past, three groups of serotonergic drugs have been epidemiolgically linked with these syndromes. They are the serotonergic vasoconstrictive anti-migraine drugs ([[ergotamine]] and [[methysergide]]),<ref>[http://books.google.com/books?id=AW7M6jBixj4C&pg=PA626&lpg=PA626&dq=ergotamine+endocardial+fibrosis&source=web&ots=BrjNzsIc-N&sig=X-WM0TaoW6I5nkx6xiTsxJYvLHo. books.google.com] Acessed May 6, 2008</ref> the serotonergic appetite suppressant drugs ([[fenfluramine]], [[chlorphentermine]], and [[aminorex]]), and certain anti-parkinsonian dopaminergic agonists, which also stimulate serotonergic 5-HT<sub>2B</sub> receptors. These include [[pergolide]] and [[cabergoline]], but not the more dopamine-specific [[lisuride]].<ref> Jähnichen S, Horowski R, Pertz H. {{PDFlink|[http://userpage.fu-berlin.de/~hpertz/Presentation001.pdf "Pergolide and Cabergoline But not Lisuride Exhibit Agonist Efficacy at Serotonin 5-HT<sub>2B</sub> Receptors".]|515&nbsp;[[Kibibyte|KiB]]<!-- application/pdf, 528029 bytes -->}} Presentation. Retrieved on [[2007-03-30]].</ref> As with fenfluramine, some of these drugs have been withdrawn from the market after groups taking them showed a statistical increase of one or more of the side effects described. An example is [[pergolide]]. The drug was in decreasing use since reported in 2003 to be associated with cardiac fibrosis.<ref>{{cite journal | url = http://www.tga.gov.au/adr/aadrb/aadr0408.htm | year = 2004 | month = August | title = Cardiac valvulopathy with pergolide | author = [[Adverse Drug Reactions Advisory Committee|ADRAC]] | journal = Aust Adv Drug React Bull | volume = 23 | issue = 4}} [http://www.tga.gov.au/adr/aadrb/aadr0408.htm Free full text] from the [[Australia]]n [[Therapeutic Goods Administration]]</ref> Two independent studies published in the [[New England Journal of Medicine]] in January 2007, implicated pergolide along with [[cabergoline]] in causing [[valvular heart disease]].<ref>{{citation| last1=Schade| first1=Rene| last2=Andersohn |first2=Frank |last3=Suissa |first3=Samy |last4=Haverkamp |first4=Wilhelm |last5=Garbe |first5=Edeltraut |title=Dopamine Agonists and the Risk of Cardiac-Valve Regurgitation |journal=New England Journal of Medicine |volume=356 |issue=1 |pages=29–38 |date=[[2007-01-04]] |year=2007 |url=http://content.nejm.org/cgi/content/full/356/1/29 |doi= |id= |pmid=17202453}}</ref><ref>{{citation| last1=Zanettini| first1=Renzo| last2=Antonini |first2=Angelo |last3=Gatto |first3=Gemma |last4=Gentile |first4=Rosa |last5=Tesei |first5=Silvana |last6=Pezzoli |first6=Gianna |title=Valvular Heart Disease and the Use of Dopamine Agonists for Parkinson's Disease |journal=New England Journal of Medicine |volume=356 |issue=1 |pages=39–46 |date=[[2007-01-04]] |year=2007 |url=http://content.nejm.org/cgi/content/full/356/1/39 |doi= |id= |pmid=17202454}}</ref> As a result of this, the [[Food and Drug Administration|FDA]] removed pergolide from the U.S. market in March, 2007.<ref>{{cite web |url=http://www.fda.gov/cder/drug/advisory/pergolide.htm |title=Food and Drug Administration Public Health Advisory |date=[[2007-03-29]] |accessdate=2007-04-27}}</ref> (Since cabergoline is not approved in the U.S. for Parkinson's Disease, but for hyperprolactinemia, the drug remains on the market. Treatment for hyperprolactinemia requires lower doses than that for Parkinson's Disease, diminishing the risk of valvular heart disease).<ref name="FDAwithdraw">{{cite web | url = http://www.fda.gov/medwatch/safety/2007/safety07.htm#Pergolide | title = MedWatch - 2007 Safety Information Alerts. Permax (pergolide) and generic equivalents | publisher = U.S. [[Food and Drug Administration]] | date = March 29, 2007 | accessdate = 2007-03-30}}</ref> Because neither the amino acid [[L-tryptophan]] nor the [[SSRI]]-class antidepressants raise blood serotonin levels {{Fact|date=April 2008}}, they are not under suspicion to cause the syndromes described. However, since 5-hydroxytryptophan ([[5-HTP]]) does raise blood serotonin levels, it is under some of the same scrutiny as actively serotonergic drugs.{{Fact|date=April 2008}} == In unicellular organisms == Serotonin is used by a variety of single-cell organisms for various purposes. Selective serotonin re-uptake inhibitors (SSRIs) have been found to be toxic to algae.<ref>{{cite journal |author=Johnson DJ, Sanderson H, Brain RA, Wilson CJ, Solomon KR |title=Toxicity and hazard of selective serotonin reuptake inhibitor antidepressants fluoxetine, fluvoxamine, and sertraline to algae |journal=Ecotoxicol. Environ. Saf. |volume=67 |issue=1 |pages=128–39 |year=2007 |pmid=16753215 |doi=10.1016/j.ecoenv.2006.03.016}}</ref> The gastrointestinal parasite ''[[Entamoeba histolytica]]'' secretes serotonin, causing a sustained secretory diarrhea in some patients.<ref>{{cite journal |author=McGowan K, Kane A, Asarkof N, ''et al'' |title=Entamoeba histolytica causes intestinal secretion: role of serotonin |journal=Science |volume=221 |issue=4612 |pages=762–4 |year=1983 |pmid=6308760| doi = 10.1126/science.6308760 <!--Retrieved from CrossRef by DOI bot-->}}</ref><ref>{{cite journal |author=McGowan K, Guerina V, Wicks J, Donowitz M |title=Secretory hormones of Entamoeba histolytica |journal=Ciba Found. Symp. |volume=112 |issue= |pages=139–54 |year=1985 |pmid=2861068 |doi=}}</ref> Patients infected with ''[[Entamoeba histolytica]]'' have been found to have highly elevated serum serotonin levels which returned to normal following resolution of the infection.<ref>{{cite journal |author=Banu, Naheed, et al. |title=Neurohumoral alterations and their role in amoebiasis. |journal=Indian J. Clin Biochem |volume=20 |issue=2 |pages=142–5 |year=2005 |url=http://medind.nic.in/iaf/t05/i2/iaft05i2p142.pdf | doi = 10.1007/BF02867414 <!--Retrieved from CrossRef by DOI bot-->}}</ref> ''[[Entamoeba histolytica]]'' also responds to the presence of serotonin by becoming more virulent.<ref>{{cite journal |author=Acharya DP, Sen MR, Sen PC |title=Effect of exogenous 5-hydroxytryptamine on pathogenicity of Entamoeba histolytica in experimental animals |journal=Indian J. Exp. Biol. |volume=27 |issue=8 |pages=718–20 |year=1989 |pmid=2561282 |doi=}}</ref> == In plants == Serotonin is found in [[mushroom]]s and [[plant]]s, including [[fruits]] and [[vegetable]]s. The highest values of 25–400 mg/kg have been found in nuts of the [[walnut]] (''Juglans'') and [[hickory]] (''Carya'') genuses. Serotonin concentrations of 3–30 mg/kg have been found in [[plantain]], [[pineapple]], [[banana]], [[kiwifruit]], [[plum]]s, and [[tomato]]es. Moderate levels from 0.1–3 mg/kg have been found in a wide range of tested vegetables.<ref>Jerome M. Feldman,Ellen M. Lee, Serotonin content of foods: effect on urinary excretion of 5-hydroxyindoleacetic acid. Am. J. Clin. Nutr. 42(4):639-43 (1985) PMID 2413754 http://www.ajcn.org/cgi/reprint/42/4/639.pdf</ref> Serotonin is one compound of the poison contained in the [[stinging hair]]s of the [[stinging nettle]] (''Urtica dioica''). It should be noted that serotonin, unlike its precursors 5-HTP and tryptophan, does not cross the [[Blood-brain barrier|blood–brain barrier]]. Several plants contain serotonin together with a family of related [[tryptamine]]s that are [[methyl]]ated at the [[amine|amino]] (NH<sub>2</sub>) and [[hydroxy]] (OH) groups, are [[amine oxide|''N''-oxides]], or miss the OH group. Examples are plants from the ''[[Anadenanthera]]'' genus that are used in the [[hallucinogen]]ic [[yopo]] snuff. == In animals == Serotonin as a [[neurotransmitter]] is found in all animals, including [[insect]]s. Several [[bufo alvarius|toad venom]]s, as well as that of the [[Brazilian wandering spider]] and [[stingray]], contain serotonin and related [[tryptamine]]s. == History == Isolated and named in 1948 by Maurice M. Rapport, Arda Green, and [[Irvine Page]] of the [[Cleveland Clinic]],<ref>{{Cite journal | author = Maurice M. Rapport, Arda A. Green, Irvine H. Page | year = 1948 | title = Serum vasoconstrictor (serotonin). IV. Isolation and characterization | journal = [[J. Biol. Chem.]] | volume = 176 | issue = 3 | pages = 1243–1251 }}</ref> the name ''serotonin'' is something of a [[misnomer]] and reflects the circumstances of the compound's discovery. It was initially identified as a vasoconstrictor substance in [[Blood plasma|blood serum]] – hence ''serotonin'', a serum agent affecting vascular tone. This agent was later chemically identified as 5-hydroxytryptamine (5-HT) by Rapport, and, as the broad range of physiological roles were elucidated, 5-HT became the preferred name in the pharmacological field. == References == {{reflist}} == External links == * [http://www.psychotropical.com/ PsychoTropicalResearch] Extensive reviews on serotonergic drugs and Serotonin Syndrome. * [http://www.chm.bris.ac.uk/motm/serotonin/home1.htm Molecule of the Month: Serotonin] at [[University of Bristol]] * Scientific America 60-Second Psych: [http://www.sciam.com/podcast/episode.cfm?id=68FC98F1-E48A-251D-8F65277181DB9A4E No Fair! My Serotonin Level Is Low]. * [http://www.clinlabnavigator.com/Tests/Serotonin.html Serotonin Test Interpretation on ClinLab Navigator]. {{Tryptamines}} {{Autacoids}} [[Category:Biogenic amines]] [[Category:Neurotransmitters]] [[Category:Tryptamines]] [[Category:Natural tryptamine alkaloids]] [[Category:Cell signaling]] [[Category:Signal transduction]] [[ar:سيروتونين]] [[bg:Серотонин]] [[ca:Serotonina]] [[cs:Serotonin]] [[da:Serotonin]] [[de:Serotonin]] [[el:Σεροτονίνη]] [[es:Serotonina]] [[fr:Sérotonine]] [[hy:Սերոտոնին]] [[hr:Serotonin]] [[id:Serotonin]] [[it:Serotonina]] [[he:סרוטונין]] [[la:Serotoninum]] [[lt:Serotoninas]] [[hu:Szerotonin]] [[nl:Serotonine]] [[ja:セロトニン]] [[no:Serotonin]] [[pl:Serotonina]] [[pt:Serotonina]] [[ru:Серотонин]] [[sl:Serotonin]] [[sr:Серотонин]] [[fi:Serotoniini]] [[sv:Serotonin]] [[tr:Serotonin]] [[uk:Серотонін]] [[zh:血清張力素]]