“Serotonin”的意思、由来-开放百科全书

Biochemically, the indoleamine molecule derives from the amino acid tryptophan, via the (rate-limiting) hydroxylation of the 5 position on the ring (forming the intermediate 5-hydroxytryptophan), and then decarboxylation to produce serotonin.^[6] Serotonin is primarily found in the enteric nervous system located in the gastrointestinal tract (GI tract). However, it is also produced in the central nervous system (CNS), specifically in the Raphe nuclei located in the brainstem. Additionally, serotonin is stored in blood platelets and is released during agitation and vasoconstriction, where it then acts as an agonist to other platelets.^[7]

Approximately 90% of the human body's total serotonin is located in the enterochromaffin cells in the GI tract, where it regulates intestinal movements.^[8]^[9] The serotonin is secreted luminally and basolaterally, which leads to increased serotonin uptake by circulating platelets and activation after stimulation, which gives increased stimulation of myenteric neurons and gastrointestinal motility.^[10] The remainder is synthesized in serotonergic neurons of the CNS, where it has various functions. These include the regulation of mood, appetite, and sleep. Serotonin also has some cognitive functions, including memory and learning. Modulation of serotonin at synapses is thought{{by whom|date=November 2018}} to be a major action of several classes of pharmacological antidepressants.

Serotonin secreted from the enterochromaffin cells eventually finds its way out of tissues into the blood. There, it is actively taken up by blood platelets, which store it. When the platelets bind to a clot, they release serotonin, where it can serve as a vasoconstrictor or a vasodilator while regulating hemostasis and blood clotting. In high concentrations, serotonin acts as a vasoconstrictor by contracting endothelial smooth muscle directly or by potentiating the effects of other vasoconstrictors (e.g. angiotensin II, norepinephrine). The vasoconstrictive property is mostly seen in pathologic states affecting the endothelium - such as atherosclerosis or chronic hypertension. In physiologic states, vasodilation occurs through the serotonin mediated release of nitric oxide from endothelial cells. Additionally, it inhibits the release of norepinephrine from adrenergic nerves.^[11] Serotonin is also a growth factor for some types of cells, which may give it a role in wound healing. There are various serotonin receptors.

Serotonin is metabolized mainly to 5-HIAA, chiefly by the liver. Metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. There follows oxidation by aldehyde dehydrogenase to 5-HIAA, the indole acetic-acid derivative. The latter is then excreted by the kidneys.

Besides mammals, serotonin is found in all bilateral animals including worms and insects, as well as in fungi and in plants. Serotonin's presence in insect venoms and plant spines serves to cause pain, which is a side-effect of serotonin injection.^[13] Serotonin is produced by pathogenic amoebae, and its effect in the human gut is diarrhea.^[14] Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds.^[15]

Functions

Serotonin is a neurotransmitter and is found in all bilateral animals including insects.^[12]

Perception of resource availability

Serotonin mediates the animal's perceptions of resources; In less complex animals, such as some invertebrates, resources simply mean food availability.^[18] In plants serotonin synthesis seems to be associated with stress signals.^[13] In more complex animals, such as arthropods and vertebrates, resources also can mean social dominance.^[20] In response to the perceived abundance or scarcity of resources, an animal's growth, reproduction or mood may be elevated or lowered. This may somewhat depend on how much serotonin the organism has at its disposal.{{citation needed|date=October 2017}}

Cellular effects

In humans, serotonin is a neurotransmitter used throughout the body having action of 14 variants of the serotonin receptor to have diverse effects on mood, anxiety, sleep, appetite, temperature, eating behaviour, sexual behaviour, movements and gastrointestinal motility.^[14] Serotonin is not administered clinically as a drug itself as it is not specific enough, however drugs that selectively target specific serotonin receptor subtypes are used therapeutically for antidepressant effects, these are called selective serotonin re-uptake inhibitors. They are dependent on serotonin availability in the synapse.^[15]

Receptors

The 5-HT receptors, the receptors for serotonin, are located on the cell membrane of 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 hallucinogenic drugs. Except for the 5-HT₃ receptor, a ligand-gated ion channel, all other 5-HT receptors are G-protein-coupled receptors (also called seven-transmembrane, or heptahelical receptors) that activate an intracellular second messenger cascade.^[16]

Termination

Serotonergic action is terminated primarily via uptake of 5-HT from the synapse. This is accomplished through the specific monoamine transporter for 5-HT, SERT, on the presynaptic neuron. Various agents can inhibit 5-HT reuptake, including cocaine, dextromethorphan (an antitussive), tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). A 2006 study conducted by the University of Washington suggested that a newly discovered monoamine transporter, known as PMAT, may account for "a significant percentage of 5-HT clearance".^[17]

Contrasting with the high-affinity SERT, the PMAT has been identified as a low-affinity transporter, with an apparent K_m of 114 micromoles/l for serotonin; approximately 230 times higher than that of SERT. However, the PMAT, despite its relatively low serotonergic affinity, has a considerably higher transport 'capacity' than SERT, "resulting in roughly comparable uptake efficiencies to SERT in heterologous expression systems.”^[17] The study also suggests some SSRIs, such as fluoxetine and sertraline anti-depressants, inhibit PMAT but at IC₅₀ values which surpass the therapeutic plasma concentrations by up to four orders of magnitude. Therefore, SSRI monotherapy is "ineffective" in PMAT inhibition. At present, no known pharmaceuticals are known to appreciably inhibit PMAT at normal therapeutic doses. The PMAT also suggestively transports dopamine and norepinephrine, albeit at K_m values even higher than that of 5-HT (330–15,000 μmoles/L).^[17]

Serotonylation

Serotonin can also signal through a nonreceptor mechanism called serotonylation, in which serotonin modifies proteins.^[27] This process underlies serotonin's effects upon platelet-forming cells (thrombocytes) in which it links to the modification of signaling enzymes called GTPases that then trigger the release of vesicle contents by exocytosis.^[18] A similar process underlies the pancreatic release of insulin.^[27]

The effects of serotonin upon vascular smooth muscle tone (this is the biological function from which serotonin originally got its name) depend upon the serotonylation of proteins involved in the contractile apparatus of muscle cells.^[19]

Nervous system

The neurons of the raphe nuclei are the principal source of 5-HT release in the brain.^[26]

There are nine raphe nuclei, designated B1-B9, which contain the majority of serotonin-containing neurons (some scientists chose to group the nuclei raphes lineares into one nucleus), all of which are located along the midline of the brainstem, and centered on the reticular formation.^[27]^[28]

Axons from the neurons of the raphe nuclei form a neurotransmitter system reaching almost every part of the central nervous system. Axons of neurons in the lower raphe nuclei terminate in the cerebellum and spinal cord, while the axons of the higher nuclei spread out in the entire brain.

Ultrastructure and Function

The serotonin nuclei may also be divided into two main groups, the rostral and caudal containing three and four nuclei respectively. The rostral group consists of the caudal linear nuclei (B8), the dorsal raphe nuclei (B6 and B7) and the median raphe nuclei (B5, B8 and B9), that project into multiple cortical and subcortical structures. The caudal group consists of the nucleus raphe magnus (B3), raphe obscurus nucleus (B2), raphe pallidus nucleus (B1), and lateral medullary reticular formation, that project into the brainstem.^[29]

Serotonergic pathway are involved in sensorimotor function, with pathways projecting both into cortical (Dorsal and Median Raphe Nuclei), subcortical, and spinal areas involved in motor activity. Pharmacological manipulation suggest that serotonergic activity increases with motor activity, while firing rates of serotonergic neurons increase with intense visual stimuli. The descending projections form a pathway that inhibits pain called the "descending inhibitory pathway" that may be relevant to disorder such as fibromyalgia, migraine and other pain disorders, and the efficacy of antidepressants in them.^[30]

Serotonergic projections from the caudal nuclei are involved in regulating mood, emotion and hypo^[31] or hyperserotonergic^[32] states may be involved in depression and sickness behavior.

Microanatomy

Serotonin is released into the synapse, or space between neurons, and diffuses over a relatively wide gap (>20 nm) to activate 5-HT receptors located on the dendrites, cell bodies and presynaptic terminals of adjacent neurons.

When humans smell food, dopamine is released to increase the appetite. But, unlike in worms, serotonin does not increase anticipatory behaviour in humans; instead, the serotonin released while consuming activates 5-HT2C receptors on dopamine-producing cells. This halts their dopamine release, and thereby serotonin decreases appetite. Drugs that block 5-HT_2C receptors make the body unable to recognize when it is no longer hungry or otherwise in need of nutrients, and are associated with weight gain,^[33] especially in people with a low number of receptors.^[34] The expression of 5-HT_2C receptors in the hippocampus follows a diurnal rhythm,^[35] just as the serotonin release in the ventromedial nucleus, which is characterised by a peak at morning when the motivation to eat is strongest.^[36]

In macaques, alpha males have twice the level of serotonin released in the brain than subordinate males and females (as measured by the levels of 5-Hydroxyindoleacetic acid (5-HIAA) in the cerebro-spinal fluid). Dominance status and cerebro-serotonin levels appear to be positively correlated. When dominant males were removed from such groups, subordinate males begin competing for dominance. Once new dominance hierarchies were established, serotonin levels of the new dominant individuals also increased to double those in subordinate males and females. The reason why serotonin levels are only high in dominant males but not dominant females has not yet been established.^[37]

In humans, levels of 5-HT_1A receptor activation in the brain show negative correlation with aggression,^[38] and a mutation in the gene that codes for the 5-HT_2A receptor may double the risk of suicide for those with that genotype.^[39] Serotonin in the brain is not usually degraded after use, but is collected by serotonergic neurons by serotonin transporters on their cell surfaces. Studies have revealed nearly 10% of total variance in anxiety-related personality depends on variations in the description of where, when and how many serotonin transporters the neurons should deploy.^[40]

Psychological influences

Serotonin has been implicated in cognition, mood, anxiety and psychosis, but strong clarity has not been achieved.^[41]^[42]

Outside the nervous system

In the digestive tract (emetic)

Serotonin regulated gastrointestinal function, the gut is surrounded by enterochromaffin cells, which release serotonin in response to food in the lumen. This makes the gut contract around the food. Platelets in the veins draining the gut collect excess serotonin. There are often serotonin abnormalities in gastrointestinal disorders like constipation and irritable bowel syndrome.^[14]

If irritants are present in the food, the enterochromaffin cells release more serotonin to make the gut move faster, i.e., to cause diarrhea, so the gut is emptied of the noxious substance. If serotonin is released in the blood faster than the platelets can absorb it, the level of free serotonin in the blood is increased. This activates 5-HT3 receptors in the chemoreceptor trigger zone that stimulate vomiting.^[43] Thus, drugs and toxins stimulate serotonin release from enterochromaffin cells in the gut wall. The enterochromaffin cells not only react to bad food but are also very sensitive to irradiation and cancer chemotherapy. Drugs that block 5HT3 are very effective in controlling the nausea and vomiting produced by cancer treatment, and are considered the gold standard for this purpose.^[44]

Bone metabolism

In mice and humans, alterations in serotonin levels and signalling have been shown to regulate bone mass.^[45]^[46]^[47]^[48] Mice that lack brain serotonin have osteopenia, while mice that lack gut serotonin have high bone density. In humans, increased blood serotonin levels have been shown to be significant negative predictor of low bone density. Serotonin can also be synthesized, albeit at very low levels, in the bone cells. It mediates its actions on bone cells using three different receptors. Through 5-HT_1B receptors, it negatively regulates bone mass, while it does so positively through 5-HT_2B receptors and 5-HT_2C receptors. There is very delicate balance between physiological role of gut serotonin and its pathology. Increase in the extracellular content of serotonin results in a complex relay of signals in the osteoblasts culminating in FoxO1/ Creb and ATF4 dependent transcriptional events.^[49] These studies have opened a new area of research in bone metabolism that can be potentially harnessed to treat bone mass disorders.^[50]

Organ development

Since serotonin signals resource availability it is not surprising that it affects organ development. Many human and animal studies have shown that nutrition in early life can influence, in adulthood, such things as body fatness, blood lipids, blood pressure, atherosclerosis, behavior, learning and longevity.^[51]

Human serotonin can also act as a growth factor directly. Liver damage increases cellular expression of 5-HT2A and 5-HT2B receptors, mediating liver compensatory regrowth (see {{section link|Liver|Regeneration and transplantation}})^[59] Serotonin present in the blood then stimulates cellular growth to repair liver damage.^[60]

5HT2B receptors also activate osteocytes, which build up bone^[61] However, serotonin also inhibits osteoblasts, through 5-HT1B receptors.^[62]

Cardiovascular growth factor

Serotonin, in addition, evokes endothelial nitric oxide synthase activation and stimulates, through a 5-HT1B receptor-mediated mechanism, the phosphorylation of p44/p42 mitogen-activated protein kinase activation in bovine aortic endothelial cell cultures.{{clarify|incomprehensible to lay readers|date=December 2018}}^[63] In blood, serotonin is collected from plasma by platelets, which store it. It is thus active wherever platelets bind in damaged tissue, as a vasoconstrictor to stop bleeding, and also as a fibrocyte mitotic (growth factor), to aid healing.^[64]

Pharmacology

Several classes of drugs target the 5-HT system, including some antidepressants, antipsychotics, anxiolytics, antiemetics, and antimigraine drugs, as well as the psychedelic drugs and empathogens.

Mechanism of Action

Serotonin is stored in vesicle in the presynaptic neurone, when stimulated by nerve impulses, serotonin is released as a neurotransmitter into the synapse, it reversibly binds to the post synaptic receptor to induce a nerve impulse on the post synaptic neurone. Serotonin can also bind to auto receptors on the presynaptic neurone to regulate the synthesis and release of serotonin. Normally serotonin is taken back into the presynaptic neurone to stop its action, it is then reused or broken down by monoamine oxidase.^[65]

Psychedelic drugs

The serotonergic psychedelic drugs psilocin/psilocybin, DMT, mescaline, psychedelic mushroom and LSD are agonists, primarily at 5HT_2A_/2C receptors.^[66]^[67]^[68] The empathogen-entactogen MDMA releases serotonin from synaptic vesicles of neurons.^[69]

Antidepressants

Drugs that alter serotonin levels are used in treating depression, generalized anxiety disorder and social phobia. Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of monoamine neurotransmitters (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 synaptic cleft longer. The tricyclic antidepressants (TCAs) inhibit the reuptake of both serotonin and norepinephrine. The newer selective serotonin reuptake inhibitors (SSRIs) have fewer side-effects and fewer interactions with other drugs.^[70]

Certain SSRI medications have been shown to lower serotonin levels below the baseline after chronic use, despite initial increases.^[71] The 5-HTTLPR gene codes for the number of serotonin transporters in the brain, with more serotonin transporters causing decreased duration and magnitude of serotonergic signaling.^[72] The 5-HTTLPR polymorphism (l/l) causing more serotonin transporters to be formed is also found to be more resilient against depression and anxiety.^[73]^[74]

Serotonin syndrome

Extremely high levels of serotonin can cause a condition known as serotonin syndrome, with toxic and potentially fatal effects. In practice, such toxic levels are essentially impossible to reach through an overdose of a single antidepressant drug, but require a combination of serotonergic agents, such as an SSRI with an MAOI.^[75] The intensity of the symptoms of serotonin syndrome vary over a wide spectrum, and the milder forms are seen even at nontoxic levels.^[76]

Antiemetics

Some 5-HT₃ antagonists, 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 the treatment of postoperative nausea and vomiting.

Other

Some serotonergic agonist drugs cause fibrosis anywhere in the body, particularly the syndrome of retroperitoneal fibrosis, as well as cardiac valve fibrosis.^[77]

In the past, three groups of serotonergic drugs have been epidemiologically linked with these syndromes. These are the serotonergic vasoconstrictive antimigraine drugs (ergotamine and methysergide),^[77] the serotonergic appetite suppressant drugs (fenfluramine, chlorphentermine, and aminorex), and certain anti-Parkinsonian dopaminergic agonists, which also stimulate serotonergic 5-HT_2B receptors. These include pergolide and cabergoline, but not the more dopamine-specific lisuride.^[78]

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 declining in use since it was reported in 2003 to be associated with cardiac fibrosis.^[79]

Two independent studies published in the New England Journal of Medicine in January 2007, implicated pergolide, along with cabergoline, in causing valvular heart disease.^[80]^[81] As a result of this, the FDA removed pergolide from the United States market in March 2007.^[82] (Since cabergoline is not approved in the United States 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).^[83]

Methyl-tryptamines and hallucinogens

Several plants contain serotonin together with a family of related tryptamines that are methylated at the amino (NH₂) and (OH) groups, are N-oxides, or miss the OH group. These compounds do reach the brain, although some portion of them are metabolized by monoamine oxidase enzymes (mainly MAO-A) in the liver. Examples are plants from the genus Anadenanthera that are used in the hallucinogenic yopo snuff. These compounds are widely present in the leaves of many plants, and may serve as deterrents for animal ingestion. Serotonin occurs in several mushrooms of the genus Panaeolus.^[84]

Comparative biology and evolution

Unicellular organisms

Serotonin is used by a variety of single-cell organisms for various purposes. SSRIs have been found to be toxic to algae.^[85] The gastrointestinal parasite Entamoeba histolytica secretes serotonin, causing a sustained secretory diarrhea in some people.^[86]^[87] Patients infected with E. histolytica have been found to have highly elevated serum serotonin levels, which returned to normal following resolution of the infection.^[88] E. histolytica also responds to the presence of serotonin by becoming more virulent.^[89] This means serotonin secretion not only serves to increase the spread of enteamoebas by giving the host diarrhea but also serves to coordinate their behaviour according to their population density, a phenomenon known as quorum sensing. Outside the gut of a host, there is nothing that the entoamoebas provoke to release serotonin, hence the serotonin concentration is very low. Low serotonin signals to the entoamoebas they are outside a host and they become less virulent to conserve energy. When they enter a new host, they multiply in the gut, and become more virulent as the enterochromaffine cells get provoked by them and the serotonin concentration increases.

Plants

In drying seeds, serotonin production is a way to get rid of the buildup of poisonous ammonia. The ammonia is collected and placed in the indole part of L-tryptophan, which is then decarboxylated by tryptophan decarboxylase to give tryptamine, which is then hydroxylated by a cytochrome P450 monooxygenase, yielding serotonin.^[90]

However, since serotonin is a major gastrointestinal tract modulator, it may be produced by plants in fruits as a way of speeding the passage of seeds through the digestive tract, in the same way as many well-known seed and fruit associated laxatives. Serotonin is found in mushrooms, fruits and vegetables. The highest values of 25–400 mg/kg have been found in nuts of the walnut (Juglans) and hickory (Carya) genera. Serotonin concentrations of 3–30 mg/kg have been found in plantains, pineapples, banana, kiwifruit, plums, and tomatoes. Moderate levels from 0.1–3 mg/kg have been found in a wide range of tested vegetables.^[91]

Serotonin is one compound of the poison contained in stinging nettles (Urtica dioica), where it causes pain on injection in the same manner as its presence in insect venoms (see below). It is also naturally found in Paramuricea clavata, or the Red Sea Fan.^[92]

Serotonin and tryptophan have been found in chocolate with varying cocoa contents. The highest serotonin content (2.93 µg/g) was found in chocolate with 85% cocoa, and the highest tryptophan content (13.27–13.34 µg/g) was found in 70–85% cocoa. The intermediate in the synthesis from tryptophan to serotonin, 5-hydroxytryptophan, was not found.^[93]

Invertebrates

Serotonin functions as a neurotransmitter in the nervous systems of most animals. For example, in the roundworm Caenorhabditis elegans, which feeds on bacteria, serotonin is released as a signal in response to positive events, such as finding a new source of food or in male animals finding a female with which to mate.^[94] When a well-fed worm feels bacteria on its cuticle, dopamine is released, which slows it down; if it is starved, serotonin also is released, which slows the animal down further. This mechanism increases the amount of time animals spend in the presence of food.^[95] The released serotonin activates the muscles used for feeding, while octopamine suppresses them.^[96] Serotonin diffuses to serotonin-sensitive neurons, which control the animal's perception of nutrient availability.

If lobsters are injected with serotonin, they behave like dominant individuals whereas octopamine causes subordinate behavior.^[97] A crayfish that is frightened may flip its tail to flee, and the effect of serotonin on this behavior depends largely on the animal's social status. Serotonin inhibits the fleeing reaction in subordinates, but enhances it in socially dominant or isolated individuals. The reason for this is social experience alters the proportion between serotonin receptors (5-HT receptors) that have opposing effects on the fight-or-flight response.{{Clarify|date=January 2012}} The effect of 5-HT₁ receptors predominates in subordinate animals, while 5-HT₂ receptors predominates in dominants.^[98]

Insects

Serotonin is evolutionarily conserved and appears across the animal kingdom. It is seen in insect processes in roles similar to in the human central nervous system, such as memory, appetite, sleep, and behavior.^[99]^[12] Locust swarming is mediated by serotonin, by transforming social preference from aversion to a gregarious state that enables coherent groups.^[100] Learning in flies and honeybees is affected by the presence of serotonin.^[101]^[102] Insect 5-HT receptors have similar sequences to the vertebrate versions, but pharmacological differences have been seen. Invertebrate drug response has been far less characterized than mammalian pharmacology and the potential for species selective insecticides has been discussed.^[103]

If flies are fed serotonin, they are more aggressive; flies depleted of serotonin still exhibit aggression, but they do so much less frequently.^[107]

Growth and reproduction

In the nematode C. elegans, artificial depletion of serotonin or the increase of octopamine cues behavior typical of a low-food environment: C. elegans becomes more active, and mating and egg-laying are suppressed, while the opposite occurs if serotonin is increased or octopamine is decreased in this animal.^[108] Serotonin is necessary for normal nematode male mating behavior,^[109] and the inclination to leave food to search for a mate.^[110] The serotonergic signaling used to adapt the worm's behaviour to fast changes in the environment affects insulin-like signaling and the TGF beta signaling pathway,^[111] which control long-term adaption.

In the fruit fly insulin both regulates blood sugar as well as acting as a growth factor. Thus, in the fruit fly, serotonergic neurons regulate the adult body size by affecting insulin secretion.^[112]^[113] Serotonin has also been identified as the trigger for swarm behavior in locusts.^[114] In humans, though insulin regulates blood sugar and IGF regulates growth, serotonin controls the release of both hormones, modulating insulin release from the beta cells in the pancreas through serotonylation of GTPase signaling proteins.^[115] Exposure to SSRIs during Pregnancy reduces fetal growth.^[116]

Genetically altered C. elegans worms that lack serotonin have an increased reproductive lifespan, may become obese, and sometimes present with arrested development at a dormant larval state.^[117]^[118]

Aging and age-related phenotypes

Serotonin is known to regulate aging, learning and memory. The first evidence comes from the study of longevity in C. elegans.^[111] During early phase of aging{{vague|date=September 2017}}, the level of serotonin increases, which alters locomotory behaviors and associative memory.^[119] The effect is restored by mutations and drugs (including mianserin and methiothepin) that inhibit serotonin receptors. The observation does not contradict with the notion that the serotonin level goes down in mammals and humans, which is typically seen in late but not early{{vague|date=September 2017}} phase of aging.

Biochemical mechanisms

Biosynthesis

In animals including humans, serotonin is synthesized from the amino acid L-tryptophan by a short metabolic pathway consisting of two enzymes, tryptophan hydroxylase (TPH) and aromatic amino acid decarboxylase (DDC), and the coenzyme pyridoxal phosphate. 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 tissues, and TPH2, which is a neuron-specific isoform.^[120]

Serotonin can be synthesized from tryptophan in the lab using Aspergillus niger and Psilocybe coprophila as catalysts. The first phase to 5-hydroxytryptophan would require letting tryptophan sit in ethanol and water for 7 days, then mixing in enough HCl (or other acid) to bring the pH to 3, and then adding NaOH to make a pH of 13 for 1 hour. Asperigillus niger would be the catalyst for this first phase. The second phase to synthesizing tryptophan itself from the 5-hydroxytryptophan intermediate would require adding ethanol and water, and letting sit for 30 days this time. The next two steps would be the same as the first phase: adding HCl to make the pH = 3, and then adding NaOH to make the pH very basic at 13 for 1 hour. This phase uses the Psilocybe coprophila as the catalyst for the reaction.^[121]

Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system, because it does not cross the blood–brain barrier.^[6] However, tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which serotonin is synthesized, does cross the blood–brain barrier. These agents are available as dietary supplements, 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 tumors or cancers, and levels of these substances may be measured in the urine to test for these tumors.

Effects of food content

Consuming purified tryptophan increases brain serotonin whereas eating foods containing tryptophan does not.^[122] This is because the transport system which brings tryptophan across the blood-brain barrier is also selective for the other amino acids contained in protein sources.^[123] High plasma levels of other large neutral amino acids compete for transport and prevent the elevated plasma tryptophan from increasing serotonin synthesis.

History and etymology

In 1935, Italian Vittorio Erspamer showed an extract from enterochromaffin cells made intestines contract. Some believed it contained adrenaline, but two years later, Erspamer was able to show it was a previously unknown amine, which he named "enteramine".^[124] In 1948, Maurice M. Rapport, Arda Green, and Irvine Page of the Cleveland Clinic discovered a vasoconstrictor substance in blood serum, and since it was a serum agent affecting vascular tone, they named it serotonin.^[125]

In 1952, enteramine was shown to be the same substance as serotonin, and as the broad range of physiological roles was elucidated, the abbreviation 5-HT of the proper chemical name 5-hydroxytryptamine became the preferred name in the pharmacological field.^[126] Synonyms of serotonin include: 5-hydroxytriptamine, thrombotin, enteramin, substance DS, and 3-(β-Aminoethyl)-5-hydroxyindole.^[127] In 1953, Betty Twarog and Page discovered serotonin in the central nervous system.^[128]

See also

Notes

1. ^{{cite journal | vauthors = Mazák K, Dóczy V, Kökösi J, Noszál B | title = Proton speciation and microspeciation of serotonin and 5-hydroxytryptophan | journal = Chemistry & Biodiversity | volume = 6 | issue = 4 | pages = 578–90 | date = April 2009 | pmid = 19353542 | doi = 10.1002/cbdv.200800087 }}
2. ^{{cite journal | vauthors = Pietra S | title = [Indolic derivatives. II. A new way to synthesize serotonin] | language = Italian | journal = Il Farmaco; Edizione Scientifica | volume = 13 | issue = 1 | pages = 75–9 | date = 1958 | pmid = 13524273 | doi = | url = }}
3. ^Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994–2011 ACD/Labs)
4. ^{{cite journal | last = Erspamer | first = Vittorio | name-list-format = vanc | title = Ricerche preliminari sulle indolalchilamine e sulle fenilalchilamine degli estratti di pelle di Anfibio |journal= Ricerca Scientifica|year= 1952|volume= 22|pages= 694–702}}
5. ^{{cite journal | last = Tammisto | first = Tapani | name-list-format = vanc | title = Increased toxicity of 5-hydroxytryptamine by ethanol in rats and mice|journal= Annales Medicinae Experimentalis et Biologiae Fenniae |date= 1967|volume= 46|issue= 3, Pt. 2|pages= 382–4}}
6. ^{{cite journal | vauthors = González-Flores D, Velardo B, Garrido M, González-Gómez D, Lozano M, Ayuso MC, Barriga C, Paredes SD, Rodríguez AB | year = 2011 | title = Ingestion of Japanese plums (Prunus salicina Lindl. cv. Crimson Globe) increases the urinary 6-sulfatoxymelatonin and total antioxidant capacity levels in young, middle-aged and elderly humans: Nutritional and functional characterization of their content | url = https://www.researchgate.net/publication/259983119 | journal = Journal of Food and Nutrition Research | volume = 50 | issue = 4| pages = 229–236 }}
7. ^{{cite journal | vauthors = Schlienger RG, Meier CR | title = Effect of selective serotonin reuptake inhibitors on platelet activation: can they prevent acute myocardial infarction? | journal = American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions | volume = 3 | issue = 3 | pages = 149–62 | date = 2003 | pmid = 14727927 | doi = 10.2165/00129784-200303030-00001 }}
8. ^{{cite web |url = http://themedicalbiochemistrypage.org/nerves.html#5ht |title = Serotonin |author = King MW |work = The Medical Biochemistry Page |publisher = Indiana University School of Medicine |accessdate = 1 December 2009}}
9. ^{{cite journal | vauthors = Berger M, Gray JA, Roth BL | title = The expanded biology of serotonin | journal = Annual Review of Medicine | volume = 60 | pages = 355–66 | year = 2009 | pmid = 19630576 | pmc = 5864293 | doi = 10.1146/annurev.med.60.042307.110802 }}
10. ^{{cite journal | vauthors = Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY | title = Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis | journal = Cell | volume = 161 | issue = 2 | pages = 264–76 | date = April 2015 | pmid = 25860609 | pmc = 4393509 | doi = 10.1016/j.cell.2015.02.047 }}
11. ^{{cite journal | vauthors = Vanhoutte PM | title = Serotonin and the vascular wall | journal = International Journal of Cardiology | volume = 14 | issue = 2 | pages = 189–203 | date = February 1987 | doi = 10.1016/0167-5273(87)90008-8 | pmid = 3818135 }}
12. ^¹{{cite journal | vauthors = Huser A, Rohwedder A, Apostolopoulou AA, Widmann A, Pfitzenmaier JE, Maiolo EM, Selcho M, Pauls D, von Essen A, Gupta T, Sprecher SG, Birman S, Riemensperger T, Stocker RF, Thum AS | title = The serotonergic central nervous system of the Drosophila larva: anatomy and behavioral function | journal = PLOS One | volume = 7 | issue = 10 | pages = e47518 | year = 2012 | pmid = 23082175 | pmc = 3474743 | doi = 10.1371/journal.pone.0047518 | bibcode = 2012PLoSO...747518H }}
13. ^¹{{cite journal | vauthors = Ramakrishna A, Giridhar P, Ravishankar GA | title = Phytoserotonin: a review | journal = Plant Signaling & Behavior | volume = 6 | issue = 6 | pages = 800–9 | year = 2011 | pmid = 21617371 | pmc = 3218476 | doi = 10.1371/journal.pone.0047518 }}
14. ^¹{{cite journal |last1=Beattie |first1=D. T. |last2=Smith |first2=J. A. M. |title=Serotonin pharmacology in the gastrointestinal tract: a review |journal=Naunyn-Schmiedeberg's Archives of Pharmacology |date=9 April 2008 |volume=377 |issue=3 |pages=181–203 |doi=10.1007/s00210-008-0276-9 |pmid=18398601 }}
15. ^{{cite journal |last1=Sangkuhl |first1=K |last2=Klein |first2=TE |last3=Altman |first3=RB |title=Selective serotonin reuptake inhibitors pathway. |journal=Pharmacogenetics and Genomics |date=November 2009 |volume=19 |issue=11 |pages=907–9 |doi=10.1097/FPC.0b013e32833132cb |pmid=19741567 |pmc=2896866 }}
16. ^{{cite journal | vauthors = Hannon J, Hoyer D | title = Molecular biology of 5-HT receptors | journal = Behavioural Brain Research | volume = 195 | issue = 1 | pages = 198–213 | date = December 2008 | pmid = 18571247 | doi = 10.1016/j.bbr.2008.03.020 }}
17. ^¹²{{cite journal | vauthors = Zhou M, Engel K, Wang J | title = Evidence for significant contribution of a newly identified monoamine transporter (PMAT) to serotonin uptake in the human brain | journal = Biochemical Pharmacology | volume = 73 | issue = 1 | pages = 147–54 | date = January 2007 | pmid = 17046718 | pmc = 1828907 | doi = 10.1016/j.bcp.2006.09.008 }}
18. ^{{cite journal | vauthors = Walther DJ, Peter JU, Winter S, Höltje M, Paulmann N, Grohmann M, Vowinckel J, Alamo-Bethencourt V, Wilhelm CS, Ahnert-Hilger G, Bader M | title = Serotonylation of small GTPases is a signal transduction pathway that triggers platelet alpha-granule release | journal = Cell | volume = 115 | issue = 7 | pages = 851–62 | date = December 2003 | pmid = 14697203 | doi = 10.1016/S0092-8674(03)01014-6 }}
19. ^{{cite journal | vauthors = Watts SW, Priestley JR, Thompson JM | title = Serotonylation of vascular proteins important to contraction | journal = PLOS One | volume = 4 | issue = 5 | pages = e5682 | date = May 2009 | pmid = 19479059 | pmc = 2682564 | doi = 10.1371/journal.pone.0005682 | bibcode = 2009PLoSO...4.5682W }}
20. ^{{cite web | title = PDSP K_i Database | work = Psychoactive Drug Screening Program (PDSP) | vauthors = Roth BL, Driscol J | url = http://pdsp.med.unc.edu/pdsp.php | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | accessdate = 17 December 2013 | date = 12 January 2011 | deadurl = yes | archiveurl = https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php | archivedate = 8 November 2013 | df = dmy-all }}
21. ^References are ignored for the functions of these receptors due to the fact they appear on the wikipedia pages for the specific receptor in question
22. ^{{cite journal | vauthors = Moro C, Edwards L, Chess-Williams R | title = 2Areceptor enhancement of contractile activity of the porcine urothelium and lamina propria | journal = International Journal of Urology | volume = 23 | issue = 11 | pages = 946–951 | date = November 2016 | pmid = 27531585 | doi = 10.1111/iju.13172 }}
23. ^{{cite web|url=http://neuronbank.org/wiki/index.php/Von_Economo_neuron|title=Von Economo neuron – NeuronBank|website=neuronbank.org}}{{MEDRS|date=October 2017}}
24. ^{{cite journal | vauthors = Gonzalez R, Chávez-Pascacio K, Meneses A | title = Role of 5-HT5A receptors in the consolidation of memory | journal = Behavioural Brain Research | volume = 252 | pages = 246–51 | date = September 2013 | pmid = 23735322 | doi = 10.1016/j.bbr.2013.05.051 }}
25. ^{{cite journal | vauthors = Nautiyal KM, Hen R | title = Serotonin receptors in depression: from A to B | journal = F1000Research | volume = 6 | pages = 123 | year = 2017 | pmid = 28232871 | pmc = 5302148 | doi = 10.12688/f1000research.9736.1 }}
26. ^{{cite book | vauthors = Frazer A, Hensler JG | veditors = Siegel GJ, Agranoff, Bernard W, Fisher SK, Albers RW, Uhler MD |title = Basic Neurochemistry | url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=bnchm|edition = Sixth|year = 1999|publisher = Lippincott Williams & Wilkins|isbn = 978-0-397-51820-3|chapter = Understanding the neuroanatomical organization of serotonergic cells in the brain provides insight into the functions of this neurotransmitter|chapterurl = https://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.|editor-link = George J. Siegel}}
27. ^{{cite book|last1=Binder|first1=Marc D.|last2=Hirokawa|first2=Nobutaka | name-list-format = vanc |title=encyclopedia of neuroscience|date=2009|publisher=Springer|location=Berlin|isbn=978-3-540-23735-8|page=705}}
28. ^The raphe nuclei group of neurons are located along the brain stem from the labels 'Mid Brain' to 'Oblongata', centered on the pons. (See relevant image.)
29. ^{{cite book|last1=Jacobs|first1=edited by Christian P. Müller, Barry|title=Handbook of the behavioral neurobiology of serotonin|date=2009|publisher=Academic|location=London|isbn=9780123746344|pages=51–59|edition=1st}}
30. ^{{cite book | chapter = Seroonin in Pain and Pain Control | last = Sommer | first = Claudia | editor-last1 = Jacobs | editor-first1 = Christian P. | editor-last2 = Müller | editor-first2 = Barry | name-list-format = vanc |title=Handbook of the behavioral neurobiology of serotonin|date=2009|publisher=Academic|location=London|isbn=9780123746344|pages=457–460|edition=1st}}
31. ^{{cite book | chapter = Serotonin in Mode and Emotions | last = Hensler | first = Julie G. | editor-last1 = Jacobs | editor-first1 = Christian P. | editor-last2 = Müller | editor-first2 = Barry | name-list-format = vanc | title=Handbook of the behavioral neurobiology of serotonin|date=2009|publisher=Academic|location=London|isbn=9780123746344|pages=367–399|edition=1st}}
32. ^{{cite journal | vauthors = Andrews PW, Bharwani A, Lee KR, Fox M, Thomson JA | title = Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response | journal = Neuroscience and Biobehavioral Reviews | volume = 51 | pages = 164–88 | date = April 2015 | pmid = 25625874 | doi = 10.1016/j.neubiorev.2015.01.018 }}
33. ^{{cite journal | vauthors = Stahl SM, Mignon L, Meyer JM | title = Which comes first: atypical antipsychotic treatment or cardiometabolic risk? | journal = Acta Psychiatrica Scandinavica | volume = 119 | issue = 3 | pages = 171–9 | date = March 2009 | pmid = 19178394 | doi = 10.1111/j.1600-0447.2008.01334.x }}
34. ^{{cite journal | vauthors = Buckland PR, Hoogendoorn B, Guy CA, Smith SK, Coleman SL, O'Donovan MC | title = Low gene expression conferred by association of an allele of the 5-HT2C receptor gene with antipsychotic-induced weight gain | journal = The American Journal of Psychiatry | volume = 162 | issue = 3 | pages = 613–5 | date = March 2005 | pmid = 15741483 | doi = 10.1176/appi.ajp.162.3.613 }}
35. ^{{cite journal | vauthors = Holmes MC, French KL, Seckl JR | title = Dysregulation of diurnal rhythms of serotonin 5-HT2C and corticosteroid receptor gene expression in the hippocampus with food restriction and glucocorticoids | journal = The Journal of Neuroscience | volume = 17 | issue = 11 | pages = 4056–65 | date = June 1997 | pmid = 9151722 | doi = 10.1523/JNEUROSCI.17-11-04056.1997 }}
36. ^{{cite journal | vauthors = Leibowitz SF | title = The role of serotonin in eating disorders | journal = Drugs | volume = 39 Suppl 3 | pages = 33–48 | year = 1990 | pmid = 2197074 | doi = 10.2165/00003495-199000393-00005 }}
37. ^McGuire, Michael (2013) "Believing, the neuroscience of fantasies, fears and confictions" (Prometius Books)
38. ^{{cite journal | vauthors = Caspi N, Modai I, Barak P, Waisbourd A, Zbarsky H, Hirschmann S, Ritsner M | title = Pindolol augmentation in aggressive schizophrenic patients: a double-blind crossover randomized study | journal = International Clinical Psychopharmacology | volume = 16 | issue = 2 | pages = 111–5 | date = March 2001 | pmid = 11236069 | doi = 10.1097/00004850-200103000-00006 }}
39. ^{{cite journal | vauthors = Ito Z, Aizawa I, Takeuchi M, Tabe M, Nakamura T | title = [Proceedings: Study of gastrointestinal motility using an extraluminal force transducer. 6. Observation of gastric and duodenal motility using synthetic motilin] | journal = Nihon Heikatsukin Gakkai Zasshi | volume = 11 | issue = 4 | pages = 244–6 | date = December 1975 | pmc = 1232434 | pmid = 1232434 }}
40. ^{{cite journal | vauthors = Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Müller CR, Hamer DH, Murphy DL | title = Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region | journal = Science | volume = 274 | issue = 5292 | pages = 1527–31 | date = November 1996 | pmid = 8929413 | doi = 10.1126/science.274.5292.1527 | bibcode = 1996Sci...274.1527L }}
41. ^{{cite journal | vauthors = Chilmonczyk Z, Bojarski AJ, Pilc A, Sylte I | title = Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands | journal = International Journal of Molecular Sciences | volume = 16 | issue = 8 | pages = 18474–506 | date = August 2015 | pmid = 26262615 | pmc = 4581256 | doi = 10.3390/ijms160818474 }}
42. ^{{cite journal | vauthors = Blier P, El Mansari M | title = Serotonin and beyond: therapeutics for major depression | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 368 | issue = 1615 | pages = 20120536 | year = 2013 | pmid = 23440470 | pmc = 3638389 | doi = 10.1098/rstb.2012.0536 }}
43. ^{{cite book | vauthors = Rang HP |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |page=187 |isbn=978-0-443-07145-4}}
44. ^{{cite journal | vauthors = de Wit R, Aapro M, Blower PR | title = Is there a pharmacological basis for differences in 5-HT3-receptor antagonist efficacy in refractory patients? | journal = Cancer Chemotherapy and Pharmacology | volume = 56 | issue = 3 | pages = 231–8 | date = September 2005 | pmid = 15838653 | doi = 10.1007/s00280-005-1033-0 }}
45. ^{{cite journal | vauthors = Frost M, Andersen TE, Yadav V, Brixen K, Karsenty G, Kassem M | title = Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin | journal = Journal of Bone and Mineral Research | volume = 25 | issue = 3 | pages = 673–5 | date = March 2010 | pmid = 20200960 | doi = 10.1002/jbmr.44 }}
46. ^{{cite journal | vauthors = Rosen CJ | title = Breaking into bone biology: serotonin's secrets | journal = Nature Medicine | volume = 15 | issue = 2 | pages = 145–6 | date = February 2009 | pmid = 19197289 | doi = 10.1038/nm0209-145 }}
47. ^{{cite journal | vauthors = Mödder UI, Achenbach SJ, Amin S, Riggs BL, Melton LJ, Khosla S | title = Relation of serum serotonin levels to bone density and structural parameters in women | journal = Journal of Bone and Mineral Research | volume = 25 | issue = 2 | pages = 415–22 | date = February 2010 | pmid = 19594297 | pmc = 3153390 | doi = 10.1359/jbmr.090721 }}
48. ^{{cite journal | vauthors = Frost M, Andersen T, Gossiel F, Hansen S, Bollerslev J, van Hul W, Eastell R, Kassem M, Brixen K | title = Levels of serotonin, sclerostin, bone turnover markers as well as bone density and microarchitecture in patients with high-bone-mass phenotype due to a mutation in Lrp5 | journal = Journal of Bone and Mineral Research | volume = 26 | issue = 8 | pages = 1721–8 | date = August 2011 | pmid = 21351148 | doi = 10.1002/jbmr.376 }}
49. ^{{cite journal | vauthors = Kode A, Mosialou I, Silva BC, Rached MT, Zhou B, Wang J, Townes TM, Hen R, DePinho RA, Guo XE, Kousteni S | title = FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin | journal = The Journal of Clinical Investigation | volume = 122 | issue = 10 | pages = 3490–503 | date = October 2012 | pmid = 22945629 | pmc = 3461930 | doi = 10.1172/JCI64906 }}
50. ^{{cite journal | vauthors = Yadav VK, Balaji S, Suresh PS, Liu XS, Lu X, Li Z, Guo XE, Mann JJ, Balapure AK, Gershon MD, Medhamurthy R, Vidal M, Karsenty G, Ducy P | title = Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis | journal = Nature Medicine | volume = 16 | issue = 3 | pages = 308–12 | date = March 2010 | pmid = 20139991 | pmc = 2836724 | doi = 10.1038/nm.2098 }}
51. ^{{cite journal|vauthors=Ozanne SE, Hales CN|title=Lifespan: catch-up growth and obesity in male mice|journal=Nature|volume=427|issue=6973|pages=411–2|date=January 2004|pmid=14749819|doi=10.1038/427411b|url=https://www.nature.com/articles/427411b|bibcode=2004Natur.427..411O}}
52. ^{{cite journal|vauthors=Lewis DS, Bertrand HA, McMahan CA, McGill HC, Carey KD, Masoro EJ|title=Preweaning food intake influences the adiposity of young adult baboons|journal=J. Clin. Invest.|volume=78|issue=4|pages=899–905|date=October 1986|pmid=3760191|pmc=423712|doi=10.1172/JCI112678}}
53. ^{{cite journal|vauthors=Hahn P|title=Effect of litter size on plasma cholesterol and insulin and some liver and adipose tissue enzymes in adult rodents|journal=J. Nutr.|volume=114|issue=7|pages=1231–4|date=July 1984|pmid=6376732|doi=10.1093/jn/114.7.1231}}
54. ^{{cite journal | vauthors = Popa D, Léna C, Alexandre C, Adrien J | title = Lasting syndrome of depression produced by reduction in serotonin uptake during postnatal development: evidence from sleep, stress, and behavior | journal = The Journal of Neuroscience | volume = 28 | issue = 14 | pages = 3546–54 | date = April 2008 | pmid = 18385313 | doi = 10.1523/JNEUROSCI.4006-07.2008 }}
55. ^{{cite journal | vauthors = Maciag D, Simpson KL, Coppinger D, Lu Y, Wang Y, Lin RC, Paul IA | title = Neonatal antidepressant exposure has lasting effects on behavior and serotonin circuitry | journal = Neuropsychopharmacology | volume = 31 | issue = 1 | pages = 47–57 | date = January 2006 | pmid = 16012532 | pmc = 3118509 | doi = 10.1038/sj.npp.1300823 }}
56. ^{{cite journal | vauthors = Maciag D, Williams L, Coppinger D, Paul IA | title = Neonatal citalopram exposure produces lasting changes in behavior which are reversed by adult imipramine treatment | journal = European Journal of Pharmacology | volume = 532 | issue = 3 | pages = 265–9 | date = February 2006 | pmid = 16483567 | pmc = 2921633 | doi = 10.1016/j.ejphar.2005.12.081 }}
57. ^{{cite journal | vauthors = Holden C | title = Neuroscience. Prozac treatment of newborn mice raises anxiety | journal = Science | volume = 306 | issue = 5697 | pages = 792 | date = October 2004 | pmid = 15514122 | doi = 10.1126/science.306.5697.792 }}
58. ^{{cite journal | vauthors = Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA | title = Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice | journal = Science | volume = 306 | issue = 5697 | pages = 879–81 | date = October 2004 | pmid = 15514160 | doi = 10.1126/science.1101678 | bibcode = 2004Sci...306..879A }}
59. ^{{cite journal | vauthors = Lesurtel M, Graf R, Aleil B, Walther DJ, Tian Y, Jochum W, Gachet C, Bader M, Clavien PA | title = Platelet-derived serotonin mediates liver regeneration | journal = Science | volume = 312 | issue = 5770 | pages = 104–7 | date = April 2006 | pmid = 16601191 | doi = 10.1126/science.1123842 | bibcode = 2006Sci...312..104L }}
60. ^{{cite journal | vauthors = Matondo RB, Punt C, Homberg J, Toussaint MJ, Kisjes R, Korporaal SJ, Akkerman JW, Cuppen E, de Bruin A | title = Deletion of the serotonin transporter in rats disturbs serotonin homeostasis without impairing liver regeneration | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 296 | issue = 4 | pages = G963–8 | date = April 2009 | pmid = 19246633 | doi = 10.1152/ajpgi.90709.2008 }}
61. ^{{cite journal | vauthors = Collet C, Schiltz C, Geoffroy V, Maroteaux L, Launay JM, de Vernejoul MC | title = The serotonin 5-HT2B receptor controls bone mass via osteoblast recruitment and proliferation | journal = FASEB Journal | volume = 22 | issue = 2 | pages = 418–27 | date = February 2008 | pmid = 17846081 | pmc = 5409955 | doi = 10.1096/fj.07-9209com }}
62. ^{{cite journal | vauthors = Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G | title = Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum | journal = Cell | volume = 135 | issue = 5 | pages = 825–37 | date = November 2008 | pmid = 19041748 | pmc = 2614332 | doi = 10.1016/j.cell.2008.09.059 | laysummary = https://www.sciencedaily.com/releases/2008/11/081126122209.htm | laysource = Science Daily }}
63. ^{{cite journal | vauthors = McDuffie JE, Motley ED, Limbird LE, Maleque MA | title = 5-hydroxytryptamine stimulates phosphorylation of p44/p42 mitogen-activated protein kinase activation in bovine aortic endothelial cell cultures | journal = Journal of Cardiovascular Pharmacology | volume = 35 | issue = 3 | pages = 398–402 | date = March 2000 | pmid = 10710124 | doi = 10.1097/00005344-200003000-00008 }}
64. ^{{cite book | last = Marieb | first = Elaine Nicpon | name-list-format = vanc | title = Essentials of Human Anatomy & Physiology | edition = Eighth|publisher = Pearson/Benjamin Cummings|location = San Francisco|year = 2009|isbn = 978-0-321-51342-7|page = 336}}
65. ^{{cite journal |last1=Fuller |first1=RW |title=Pharmacology of central serotonin neurons. |journal=Annual Review of Pharmacology and Toxicology |date=1980 |volume=20 |pages=111–27 |doi=10.1146/annurev.pa.20.040180.000551 |pmid=6992697 }}
66. ^{{cite journal | vauthors = Titeler M, Lyon RA, Glennon RA | title = Radioligand binding evidence implicates the brain 5-HT2 receptor as a site of action for LSD and phenylisopropylamine hallucinogens | journal = Psychopharmacology | volume = 94 | issue = 2 | pages = 213–6 | year = 1988 | pmid = 3127847 | doi = 10.1007/BF00176847 }}
67. ^{{cite book | vauthors = Nichols DE | veditors = Baumgarten HG, Gothert M |title = Serotoninergic Neurons and 5-HT Receptors in the CNS|publisher = Springer-Verlag TELOS|location = Santa Clara, CA|year = 2000|isbn = 978-3-540-66715-5|chapter = Role of serotonergic neurons and 5-HT receptors in the action of hallucinogens}}
68. ^{{cite journal | vauthors = Kapur S, Seeman P | title = NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia | journal = Molecular Psychiatry | volume = 7 | issue = 8 | pages = 837–44 | year = 2002 | pmid = 12232776 | doi = 10.1038/sj.mp.4001093 }}
69. ^{{cite journal | vauthors = Johnson MP, Hoffman AJ, Nichols DE | title = Effects of the enantiomers of MDA, MDMA and related analogues on [3H]serotonin and [3H]dopamine release from superfused rat brain slices | journal = European Journal of Pharmacology | volume = 132 | issue = 2–3 | pages = 269–76 | date = December 1986 | pmid = 2880735 | doi = 10.1016/0014-2999(86)90615-1 }}
70. ^{{Cite book | last1 = Goodman | first1 = Louis Sanford | last2 = Brunton | first2 = Laurence L. | last3 = Chabner | first3 = Bruce | last4 = Knollmann | first4 = Björn C. | name-list-format = vanc | title = Goodman and Gilman's pharmacological basis of therapeutics | year = 2001 | publisher = McGraw-Hill | location = New York | isbn = 978-0-07-162442-8 | pages = 459–461 }}
71. ^{{cite journal | vauthors = Benmansour S, Cecchi M, Morilak DA, Gerhardt GA, Javors MA, Gould GG, Frazer A | title = Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level | journal = The Journal of Neuroscience | volume = 19 | issue = 23 | pages = 10494–501 | date = December 1999 | pmid = 10575045 | doi = 10.1523/JNEUROSCI.19-23-10494.1999 }}
72. ^{{cite journal | vauthors = Beitchman JH, Baldassarra L, Mik H, De Luca V, King N, Bender D, Ehtesham S, Kennedy JL | title = Serotonin transporter polymorphisms and persistent, pervasive childhood aggression | journal = The American Journal of Psychiatry | volume = 163 | issue = 6 | pages = 1103–5 | date = June 2006 | pmid = 16741214 | doi = 10.1176/appi.ajp.163.6.1103 }}
73. ^{{cite journal | vauthors = Pezawas L, Meyer-Lindenberg A, Drabant EM, Verchinski BA, Munoz KE, Kolachana BS, Egan MF, Mattay VS, Hariri AR, Weinberger DR | title = 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression | journal = Nature Neuroscience | volume = 8 | issue = 6 | pages = 828–34 | date = June 2005 | pmid = 15880108 | doi = 10.1038/nn1463 }}
74. ^{{cite journal | vauthors = Schinka JA, Busch RM, Robichaux-Keene N | title = A meta-analysis of the association between the serotonin transporter gene polymorphism (5-HTTLPR) and trait anxiety | journal = Molecular Psychiatry | volume = 9 | issue = 2 | pages = 197–202 | date = February 2004 | pmid = 14966478 | doi = 10.1038/sj.mp.4001405 }}
75. ^{{cite journal | vauthors = Isbister GK, Bowe SJ, Dawson A, Whyte IM | title = Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose | journal = Journal of Toxicology. Clinical Toxicology | volume = 42 | issue = 3 | pages = 277–85 | year = 2004 | pmid = 15362595 | doi = 10.1081/CLT-120037428 }}
76. ^{{cite journal | vauthors = Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM | title = The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity | journal = QJM | volume = 96 | issue = 9 | pages = 635–42 | date = September 2003 | pmid = 12925718 | doi = 10.1093/qjmed/hcg109 }}
77. ^¹{{cite book | vauthors = Baskin SI|title = Principles of cardiac toxicology|publisher = CRC Press|location = Boca Raton|year = 1991|isbn = 978-0-8493-8809-5|url = https://books.google.com/?id=AW7M6jBixj4C&pg=PA626|accessdate = 3 February 2010}}
78. ^{{cite web|url = http://userpage.fu-berlin.de/~hpertz/Presentation001.pdf|title = Pergolide and Cabergoline But not Lisuride Exhibit Agonist Efficacy at Serotonin 5-HT_2B Receptors| vauthors = Jähnichen S, Horowski R, Pertz H |accessdate = 3 February 2010}}
79. ^{{cite journal |year=2004 |title=Cardiac valvulopathy with pergolide |journal=Aust Adv Drug React Bull |volume=23 |issue=4 | author = Adverse Drug Reactions Advisory Committee, Australia |url=http://www.tga.gov.au/adr/aadrb/aadr0408.htm | dead-url = yes | archive-url = https://web.archive.org/web/20120627200919/http://www.tga.gov.au/adr/aadrb/aadr0408.htm |archivedate=27 June 2012 }}
80. ^{{cite journal | vauthors = Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E | title = Dopamine agonists and the risk of cardiac-valve regurgitation | journal = The New England Journal of Medicine | volume = 356 | issue = 1 | pages = 29–38 | date = January 2007 | pmid = 17202453 | doi = 10.1056/NEJMoa062222 }}
81. ^{{cite journal | vauthors = Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G | title = Valvular heart disease and the use of dopamine agonists for Parkinson's disease | journal = The New England Journal of Medicine | volume = 356 | issue = 1 | pages = 39–46 | date = January 2007 | pmid = 17202454 | doi = 10.1056/NEJMoa054830 }}
82. ^{{cite web |url=http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm152695.htm |title=Food and Drug Administration Public Health Advisory |date=29 March 2007 |accessdate=7 February 2010}}
83. ^{{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 = United States Food and Drug Administration|date = 29 March 2007|accessdate = 30 March 2007}}
84. ^{{cite journal | vauthors = Tyler VE | title = Occurrence of serotonin in a hallucinogenic mushroom | journal = Science | volume = 128 | issue = 3326 | pages = 718 | date = September 1958 | pmid = 13580242 | doi = 10.1126/science.128.3326.718 | bibcode = 1958Sci...128..718T }}
85. ^{{cite journal | vauthors = 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 = Ecotoxicology and Environmental Safety | volume = 67 | issue = 1 | pages = 128–39 | date = May 2007 | pmid = 16753215 | doi = 10.1016/j.ecoenv.2006.03.016 }}
86. ^¹{{cite journal | vauthors = McGowan K, Kane A, Asarkof N, Wicks J, Guerina V, Kellum J, Baron S, Gintzler AR, Donowitz M | title = Entamoeba histolytica causes intestinal secretion: role of serotonin | journal = Science | volume = 221 | issue = 4612 | pages = 762–4 | date = August 1983 | pmid = 6308760 | doi = 10.1126/science.6308760 | bibcode = 1983Sci...221..762M }}
87. ^{{cite book | vauthors = McGowan K, Guerina V, Wicks J, Donowitz M | title = Secretory hormones of Entamoeba histolytica | journal = Ciba Foundation Symposium | volume = 112 | pages = 139–54 | year = 1985 | pmid = 2861068 | doi = 10.1002/9780470720936.ch8 | series = Novartis Foundation Symposia | isbn = 9780470720936 }}
88. ^{{cite journal | vauthors = Banu N, Zaidi KR, Mehdi G, Mansoor T | title = Neurohumoral alterations and their role in amoebiasis | journal = Indian Journal of Clinical Biochemistry | volume = 20 | issue = 2 | pages = 142–5 | date = July 2005 | pmid = 23105547 | pmc = 3453840 | doi = 10.1007/BF02867414 }}
89. ^{{cite journal | vauthors = Acharya DP, Sen MR, Sen PC | title = Effect of exogenous 5-hydroxytryptamine on pathogenicity of Entamoeba histolytica in experimental animals | journal = Indian Journal of Experimental Biology | volume = 27 | issue = 8 | pages = 718–20 | date = August 1989 | pmid = 2561282 }}
90. ^{{cite book | vauthors = Schröder P, Abele C, Gohr P, Stuhlfauth-Roisch U, Grosse W | title = Latest on enzymology of serotonin biosynthesis in walnut seeds | volume = 467 | pages = 637–44 | year = 1999 | pmid = 10721112 | doi = 10.1007/978-1-4615-4709-9_81 | isbn = 978-0-306-46204-7 | series = Advances in Experimental Medicine and Biology }}
91. ^¹{{cite journal | vauthors = Feldman JM, Lee EM | title = Serotonin content of foods: effect on urinary excretion of 5-hydroxyindoleacetic acid | journal = The American Journal of Clinical Nutrition | volume = 42 | issue = 4 | pages = 639–43 | date = October 1985 | pmid = 2413754 | url = http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=2413754 | doi = 10.1093/ajcn/42.4.639 }}
92. ^{{cite journal | vauthors = Pénez N, Culioli G, Pérez T, Briand JF, Thomas OP, Blache Y | title = Antifouling properties of simple indole and purine alkaloids from the Mediterranean gorgonian Paramuricea clavata | journal = Journal of Natural Products | volume = 74 | issue = 10 | pages = 2304–8 | date = October 2011 | pmid = 21939218 | doi = 10.1021/np200537v }}
93. ^{{cite journal | vauthors = Guillén-Casla V, Rosales-Conrado N, León-González ME, Pérez-Arribas LV, Polo-Díez LM | title = Determination of serotonin and its precursors in chocolate samples by capillary liquid chromatography with mass spectrometry detection | journal = Journal of Chromatography A | volume = 1232 | issue = | pages = 158–65 | date = April 2012 | pmid = 22186492 | doi = 10.1016/j.chroma.2011.11.037 }}
94. ^Jonz, Michael G.Riga, EkateriniMercier, A. JoffrePotter, John W. "Effects Of 5-HT (Serotonin) On Reproductive Behaviour In Heterodera Schachtii (Nematoda)." Canadian Journal of Zoology 79.9 (2001): 1727. Canadian Reference Centre. Web. 11 August 2013.
95. ^{{cite journal | vauthors = Sawin ER, Ranganathan R, Horvitz HR | title = C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway | journal = Neuron | volume = 26 | issue = 3 | pages = 619–31 | date = June 2000 | pmid = 10896158 | doi = 10.1016/S0896-6273(00)81199-X }}
96. ^{{cite journal | vauthors = Niacaris T, Avery L | title = Serotonin regulates repolarization of the C. elegans pharyngeal muscle | journal = The Journal of Experimental Biology | volume = 206 | issue = Pt 2 | pages = 223–31 | date = January 2003 | pmid = 12477893 | pmc = 4441752 | doi = 10.1242/jeb.00101 }}
97. ^¹{{cite journal | vauthors = Kravitz EA | title = Hormonal control of behavior: amines and the biasing of behavioral output in lobsters | journal = Science | volume = 241 | issue = 4874 | pages = 1775–81 | date = September 1988 | pmid = 2902685 | doi = 10.1126/science.2902685 | bibcode = 1988Sci...241.1775K }}
98. ^{{cite journal | vauthors = Yeh SR, Fricke RA, Edwards DH | title = The effect of social experience on serotonergic modulation of the escape circuit of crayfish | journal = Science | volume = 271 | issue = 5247 | pages = 366–9 | date = January 1996 | pmid = 8553075 | doi = 10.1126/science.271.5247.366 | url = http://www.cns.nyu.edu/events/spf/SPF_papers/yehetal1996.pdf | bibcode = 1996Sci...271..366Y | citeseerx = 10.1.1.470.6528 }}
99. ^{{cite journal |doi=10.14800/nt.314 |title=Serotonin, serotonin receptors and their actions in insects |journal=Neurotransmitter |year=2015 |volume=2 |pages=1–14 }}
100. ^{{cite journal | vauthors = Anstey ML, Rogers SM, Ott SR, Burrows M, Simpson SJ | title = Serotonin mediates behavioral gregarization underlying swarm formation in desert locusts | journal = Science | volume = 323 | issue = 5914 | pages = 627–30 | date = January 2009 | pmid = 19179529 | doi = 10.1126/science.1165939 | bibcode = 2009Sci...323..627A }}
101. ^{{cite journal | vauthors = Sitaraman D, LaFerriere H, Birman S, Zars T | title = Serotonin is critical for rewarded olfactory short-term memory in Drosophila | journal = Journal of Neurogenetics | volume = 26 | issue = 2 | pages = 238–44 | date = June 2012 | pmid = 22436011 | doi = 10.3109/01677063.2012.666298 }}
102. ^{{cite journal | vauthors = Bicker G, Menzel R | title = Chemical codes for the control of behaviour in arthropods | journal = Nature | volume = 337 | issue = 6202 | pages = 33–9 | date = January 1989 | pmid = 2562906 | doi = 10.1038/337033a0 | bibcode = 1989Natur.337...33B }}
103. ^{{cite journal | vauthors = Cai M, Li Z, Fan F, Huang Q, Shao X, Song G | title = Design and synthesis of novel insecticides based on the serotonergic ligand 1-[(4-aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine (PAPP) | journal = Journal of Agricultural and Food Chemistry | volume = 58 | issue = 5 | pages = 2624–9 | date = March 2010 | pmid = 20000410 | doi = 10.1021/jf902640u }}
104. ^{{cite book |first1=Stanley E. |last1=Manahan | name-list-format = vanc |title=Toxicological Chemistry and Biochemistry |edition=3rd |publisher=CRC Press |year=2002 |isbn=978-1-4200-3212-3 |page=393 }}
105. ^¹{{cite journal | vauthors = Chen J, Lariviere WR | title = The nociceptive and anti-nociceptive effects of bee venom injection and therapy: a double-edged sword | journal = Progress in Neurobiology | volume = 92 | issue = 2 | pages = 151–83 | year = 2010 | pmid = 20558236 | pmc = 2946189 | doi = 10.1016/j.pneurobio.2010.06.006 }}
106. ^{{cite book |last1=Postma |first1=Terri L | name-list-format = vanc |chapter=Neurotoxic Animal Poisons and Venoms |chapterurl=http://www.sciencedirect.com/science/article/pii/B9780323052603500496 |pages=463–89 |editor1-first=Michael R. |editor1-last=Dobbs |year=2009 |title=Clinical Neurotoxicology |isbn=978-0-323-05260-3 }}
107. ^{{cite journal | vauthors = Dierick HA, Greenspan RJ | title = Serotonin and neuropeptide F have opposite modulatory effects on fly aggression | journal = Nature Genetics | volume = 39 | issue = 5 | pages = 678–82 | date = May 2007 | pmid = 17450142 | doi = 10.1038/ng2029 }}
108. ^¹{{cite journal | vauthors = Srinivasan S, Sadegh L, Elle IC, Christensen AG, Faergeman NJ, Ashrafi K | title = Serotonin regulates C. elegans fat and feeding through independent molecular mechanisms | journal = Cell Metabolism | volume = 7 | issue = 6 | pages = 533–44 | date = June 2008 | pmid = 18522834 | pmc = 2495008 | doi = 10.1016/j.cmet.2008.04.012 }}
109. ^{{cite journal | vauthors = Loer CM, Kenyon CJ | title = Serotonin-deficient mutants and male mating behavior in the nematode Caenorhabditis elegans | journal = The Journal of Neuroscience | volume = 13 | issue = 12 | pages = 5407–17 | date = December 1993 | pmid = 8254383 | doi = 10.1523/JNEUROSCI.13-12-05407.1993 }}
110. ^{{cite journal | vauthors = Lipton J, Kleemann G, Ghosh R, Lints R, Emmons SW | title = Mate searching in Caenorhabditis elegans: a genetic model for sex drive in a simple invertebrate | journal = The Journal of Neuroscience | volume = 24 | issue = 34 | pages = 7427–34 | date = August 2004 | pmid = 15329389 | doi = 10.1523/JNEUROSCI.1746-04.2004 }}
111. ^¹{{cite journal | vauthors = Murakami H, Murakami S | title = Serotonin receptors antagonistically modulate Caenorhabditis elegans longevity | journal = Aging Cell | volume = 6 | issue = 4 | pages = 483–8 | date = August 2007 | pmid = 17559503 | doi = 10.1111/j.1474-9726.2007.00303.x }}
112. ^{{cite journal | vauthors = Kaplan DD, Zimmermann G, Suyama K, Meyer T, Scott MP | title = A nucleostemin family GTPase, NS3, acts in serotonergic neurons to regulate insulin signaling and control body size | journal = Genes & Development | volume = 22 | issue = 14 | pages = 1877–93 | date = July 2008 | pmid = 18628395 | pmc = 2492735 | doi = 10.1101/gad.1670508 }}
113. ^{{cite journal | vauthors = Ruaud AF, Thummel CS | title = Serotonin and insulin signaling team up to control growth in Drosophila | journal = Genes & Development | volume = 22 | issue = 14 | pages = 1851–5 | date = July 2008 | pmid = 18628391 | pmc = 2735276 | doi = 10.1101/gad.1700708 }}
114. ^{{cite journal | vauthors = Anstey ML, Rogers SM, Ott SR, Burrows M, Simpson SJ | title = Serotonin mediates behavioral gregarization underlying swarm formation in desert locusts | journal = Science | volume = 323 | issue = 5914 | pages = 627–30 | date = January 2009 | pmid = 19179529 | doi = 10.1126/science.1165939 | laysummary = http://news.bbc.co.uk/2/hi/science/nature/7858996.stm | laysource = BBC News | bibcode = 2009Sci...323..627A }}
115. ^¹²{{cite journal | vauthors = Paulmann N, Grohmann M, Voigt JP, Bert B, Vowinckel J, Bader M, Skelin M, Jevsek M, Fink H, Rupnik M, Walther DJ | title = Intracellular serotonin modulates insulin secretion from pancreatic beta-cells by protein serotonylation | journal = PLOS Biology | volume = 7 | issue = 10 | pages = e1000229 | date = October 2009 | pmid = 19859528 | pmc = 2760755 | doi = 10.1371/journal.pbio.1000229 | editor1-last = O'Rahilly | editor1-first = Steve }}
116. ^{{cite journal | vauthors = Davidson S, Prokonov D, Taler M, Maayan R, Harell D, Gil-Ad I, Weizman A | title = Effect of exposure to selective serotonin reuptake inhibitors in utero on fetal growth: potential role for the IGF-I and HPA axes | journal = Pediatric Research | volume = 65 | issue = 2 | pages = 236–41 | date = February 2009 | pmid = 19262294 | doi = 10.1203/PDR.0b013e318193594a }}
117. ^{{cite journal | vauthors = Ben Arous J, Laffont S, Chatenay D | title = Molecular and sensory basis of a food related two-state behavior in C. elegans | journal = PLOS One | volume = 4 | issue = 10 | pages = e7584 | date = October 2009 | pmid = 19851507 | pmc = 2762077 | doi = 10.1371/journal.pone.0007584 | editor1-last = Brezina | bibcode = 2009PLoSO...4.7584B | editor1-first = Vladimir }}
118. ^{{cite journal | vauthors = Sze JY, Victor M, Loer C, Shi Y, Ruvkun G | title = Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant | journal = Nature | volume = 403 | issue = 6769 | pages = 560–4 | date = February 2000 | pmid = 10676966 | doi = 10.1038/35000609 | bibcode = 2000Natur.403..560S }}
119. ^{{cite journal | vauthors = Murakami H, Bessinger K, Hellmann J, Murakami S | title = Manipulation of serotonin signal suppresses early phase of behavioral aging in Caenorhabditis elegans | journal = Neurobiology of Aging | volume = 29 | issue = 7 | pages = 1093–100 | date = July 2008 | pmid = 17336425 | doi = 10.1016/j.neurobiolaging.2007.01.013 }}
120. ^{{cite journal | vauthors = Côté F, Thévenot E, Fligny C, Fromes Y, Darmon M, Ripoche MA, Bayard E, Hanoun N, Saurini F, Lechat P, Dandolo L, Hamon M, Mallet J, Vodjdani G | title = Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 23 | pages = 13525–30 | date = November 2003 | pmid = 14597720 | pmc = 263847 | doi = 10.1073/pnas.2233056100 | first14 = G | bibcode = 2003PNAS..10013525C }}
121. ^{{cite journal | vauthors = Alarcon J | year = 2008 | title = Biotransformation of indole derivatives by mycelial cultures | url = | journal = Zeitschrift für Naturforschung C | volume = 63 | issue = 1–2| page = 82 | doi=10.1515/znc-2008-1-215}}
122. ^{{cite journal | vauthors = Wurtman RJ, Hefti F, Melamed E | title = Precursor control of neurotransmitter synthesis | journal = Pharmacological Reviews | volume = 32 | issue = 4 | pages = 315–35 | date = December 1980 | pmid = 6115400 }}
123. ^¹²{{cite journal | vauthors = Young SN | title = How to increase serotonin in the human brain without drugs | journal = Journal of Psychiatry & Neuroscience | volume = 32 | issue = 6 | pages = 394–9 | date = November 2007 | pmid = 18043762 | pmc = 2077351 }}
124. ^{{cite journal | vauthors = Negri L | title = [Vittorio Erspamer (1909–1999)] | journal = Medicina Nei Secoli | volume = 18 | issue = 1 | pages = 97–113 | year = 2006 | pmid = 17526278 | url = https://www.medicinaneisecoli.it/index.php/MedSecoli/article/view/491 }}
125. ^{{cite journal | vauthors = Rapport MM, Green AA, Page IH | title = Serum vasoconstrictor, serotonin; isolation and characterization | journal = The Journal of Biological Chemistry | volume = 176 | issue = 3 | pages = 1243–51 | date = December 1948 | pmid = 18100415 | url = http://www.jbc.org/content/176/3/1243.short }}
126. ^{{cite journal | vauthors = Feldberg W, Toh CC | title = Distribution of 5-hydroxytryptamine (serotonin, enteramine) in the wall of the digestive tract | journal = The Journal of Physiology | volume = 119 | issue = 2–3 | pages = 352–62 | date = February 1953 | pmid = 13035756 | pmc = 1392800 | doi = 10.1113/jphysiol.1953.sp004850 }}
127. ^SciFinder – Serotonin Substance Detail. Accessed (4 November 2012).{{full citation needed|date=October 2017}}
128. ^{{cite journal | vauthors = Twarog BM, Page IH | title = Serotonin content of some mammalian tissues and urine and a method for its determination | journal = The American Journal of Physiology | volume = 175 | issue = 1 | pages = 157–61 | date = October 1953 | pmid = 13114371 | doi = 10.1152/ajplegacy.1953.175.1.157 | url = http://ajplegacy.physiology.org/content/175/1/157 }}