Serotonin
5-HTP | |
Biosynthesis | Aromatic L-amino acid decarboxylase |
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Metabolism | MAO |
Identifiers | |
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ECHA InfoCard | 100.000.054 |
Names | |
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IUPAC name
5-Hydroxytryptamine
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Preferred IUPAC name
3-(2-Aminoethyl)-1H-indol-5-ol | |
Other names
5-Hydroxytryptamine, 5-HT, Enteramine; Thrombocytin, 3-(β-Aminoethyl)-5-hydroxyindole, 3-(2-Aminoethyl)indol-5-ol, Thrombotonin
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Identifiers | |
3D model (
JSmol ) |
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ChEBI | |
ChEMBL | |
ChemSpider | |
ECHA InfoCard
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100.000.054 |
IUPHAR/BPS |
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KEGG | |
MeSH | Serotonin |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C10H12N2O | |
Molar mass | 176.215 g/mol |
Appearance | White powder |
Melting point | 167.7 °C (333.9 °F; 440.8 K) 121–122 °C (ligroin)[3] |
Boiling point | 416 ± 30 °C (at 760 Torr)[1] |
slightly soluble | |
Acidity (pKa) | 10.16 in water at 23.5 °C[2] |
2.98 D | |
Hazards | |
Lethal dose or concentration (LD, LC): | |
LD50 (median dose)
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750 mg/kg (subcutaneous, rat),[4] 4500 mg/kg (intraperitoneal, rat),[5] 60 mg/kg (oral, rat) |
Safety data sheet (SDS) | External MSDS |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Serotonin (/ˌsɛrəˈtoʊnɪn, ˌsɪərə-/)[6][7][8] or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex, touching on diverse functions including mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vasoconstriction.[9]
Serotonin is produced in the
The serotonin is secreted
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
Biochemically, the
Besides mammals, serotonin is found in all
Molecular structure
Biochemically, the
Crystal structure
Serotonin crystallizes in P212121 chiral space group forming different hydrogen-bonding interactions between serotonin molecules via N-H...O and O-H...N intermolecular bonds.[25] Serotonin also forms several salts, including pharmaceutical formulation of serotonin adipate.[26]
Biological role
Serotonin is involved in numerous physiological processes,
Cellular effects
Serotonin primarily acts through its receptors and its effects depend on which cells and tissues express these receptors.[30]
Metabolism involves first
Receptors
The 5-HT receptors, the
Termination
Serotonergic action is terminated primarily via
In contrast to the high affinity of SERT, the PMAT has been identified as a low-affinity transporter, with an apparent Km of 114 micromoles/l for serotonin, which is 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."[38] The study also suggests that the administration of SSRIs such as fluoxetine and sertraline may be associated with an inhibitory effect on PMAT activity when used at higher than normal dosages (IC50 test values used in trials were 3–4 fold higher than typical prescriptive dosage).
Serotonylation
Serotonin can also signal through a nonreceptor mechanism called serotonylation, in which serotonin modifies proteins.
The effects of serotonin upon vascular smooth muscle tone – the biological function after which serotonin was originally named – depend upon the serotonylation of proteins involved in the contractile apparatus of muscle cells.[41]
Receptor | Ki (nM)[42] | Receptor function[Note 1] |
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5-HT1 receptor family signals via Gi/o inhibition of adenylyl cyclase. | ||
5-HT1A | 3.17 | Memory[vague] (agonists ↓); learning[vague] (agonists ↓); anxiety (agonists ↓); depression (agonists ↓); positive, negative, and cognitive symptoms of schizophrenia (partial agonists ↓); analgesia (agonists ↑); aggression (agonists ↓); dopamine release in the prefrontal cortex (agonists ↑); serotonin release and synthesis (agonists ↓) |
5-HT1B | 4.32 | Vasoconstriction (agonists ↑); aggression (agonists ↓); bone mass (↓). Serotonin autoreceptor. |
5-HT1D | 5.03 | Vasoconstriction (agonists ↑) |
5-HT1E | 7.53 | |
5-HT1F | 10 | |
5-HT2 receptor family signals via Gq activation of phospholipase C. | ||
5-HT2A | 11.55 | Psychedelia (agonists ↑); depression (agonists & antagonists ↓); anxiety (antagonists ↓); positive and negative symptoms of schizophrenia (antagonists ↓); norepinephrine release from the locus coeruleus (antagonists ↑); glutamate release in the prefrontal cortex (agonists ↑); dopamine in the prefrontal cortex (agonists ↑);[43] urinary bladder contractions (agonists ↑)[44] |
5-HT2B | 8.71 | Cardiovascular functioning (agonists increase risk of pulmonary hypertension), empathy (via von Economo neurons[45] )
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5-HT2C | 5.02 | Dopamine release into the mesocorticolimbic pathway (agonists ↓); acetylcholine release in the prefrontal cortex (agonists ↑); dopaminergic and noradrenergic activity in the frontal cortex (antagonists ↑);[46] appetite (agonists ↓); antipsychotic effects (agonists ↑); antidepressant effects (agonists & antagonists ↑)
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Other 5-HT receptors | ||
5-HT3 | 593 | Emesis (agonists ↑); anxiolysis (antagonists ↑). |
5-HT4 | 125.89 | Movement of food across the GI tract (agonists ↑); memory & learning (agonists ↑); antidepressant effects (agonists ↑). Signalling via Gαs activation of adenylyl cyclase. |
5-HT5A | 251.2 | Memory consolidation.[47] Signals via Gi/o inhibition of adenylyl cyclase. |
5-HT6 | 98.41 | Cognition (antagonists ↑); antidepressant effects (agonists & antagonists ↑); anxiogenic effects (antagonists ↑[48]). Gs signalling via activating adenylyl cyclase. |
5-HT7 | 8.11 | Cognition (antagonists ↑); antidepressant effects (antagonists ↑). Acts by Gs signalling via activating adenylyl cyclase. |
Nervous system
The neurons of the
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.[52]
The serotonergic pathway is 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 suggests that serotonergic activity increases with motor activity while firing rates of serotonergic neurons increase with intense visual stimuli. Animal models suggest that kainate signaling negatively regulates serotonin actions in the retina, with possible implications for the control of the visual system.[53] The descending projections form a pathway that inhibits pain called the "descending inhibitory pathway" that may be relevant to a disorder such as fibromyalgia, migraine, and other pain disorders, and the efficacy of antidepressants in them.[54]
Serotonergic projections from the caudal nuclei are involved in regulating mood and emotion, and hypo-[55] or hyper-serotonergic[56] 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
When humans smell food, dopamine is released to
In macaques, alpha males have twice the level of serotonin in the brain as subordinate males and females (measured by the concentration of 5-HIAA in the cerebrospinal fluid (CSF)). Dominance status and CSF 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.[61]
In humans, levels of 5-HT1A receptor inhibition in the brain show negative correlation with aggression,[62] and a mutation in the gene that codes for the 5-HT2A receptor may double the risk of suicide for those with that genotype.[63] 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.[64]
Outside the nervous system
Digestive tract (emetic)
Serotonin regulates gastrointestinal (GI) 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 such as constipation and irritable bowel syndrome.[65]
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
Lungs
The
Skin
Serotonin is also produced by Merkel cells which are part of the somatosensory system.[71]
Bone metabolism
In mice and humans, alterations in serotonin levels and signalling have been shown to regulate bone mass.[72][73][74][75] 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 a 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-HT1B receptors, it negatively regulates bone mass, while it does so positively through 5-HT2B receptors and 5-HT2C 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.[76] Following the 2008 findings that gut serotonin regulates bone mass, the mechanistic investigations into what regulates serotonin synthesis from the gut in the regulation of bone mass have started. Piezo1 has been shown to sense RNA in the gut and relay this information through serotonin synthesis to the bone by acting as a sensor of single-stranded RNA (ssRNA) governing 5-HT production. Intestinal epithelium-specific deletion of mouse Piezo1 profoundly disturbed gut peristalsis, impeded experimental colitis, and suppressed serum 5-HT levels. Because of systemic 5-HT deficiency, conditional knockout of Piezo1 increased bone formation. Notably, fecal ssRNA was identified as a natural Piezo1 ligand, and ssRNA-stimulated 5-HT synthesis from the gut was evoked in a MyD88/TRIF-independent manner. Colonic infusion of RNase A suppressed gut motility and increased bone mass. These findings suggest gut ssRNA as a master determinant of systemic 5-HT levels, indicating the ssRNA-Piezo1 axis as a potential prophylactic target for treatment of bone and gut disorders. Studies in 2008, 2010 and 2019 have opened the potential for serotonin research to treat bone mass disorders.[77][78]
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.[79][80][81] Rodent experiment shows that neonatal exposure to SSRIs makes persistent changes in the serotonergic transmission of the brain resulting in behavioral changes,[82][83] which are reversed by treatment with antidepressants.[84] By treating normal and knockout mice lacking the serotonin transporter with fluoxetine scientists showed that normal emotional reactions in adulthood, like a short latency to escape foot shocks and inclination to explore new environments were dependent on active serotonin transporters during the neonatal period.[85][86]
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 Liver § Regeneration and transplantation)[87] Serotonin present in the blood then stimulates cellular growth to repair liver damage.[88] 5HT2B receptors also activate osteocytes, which build up bone[89] However, serotonin also inhibits osteoblasts, through 5-HT1B receptors.[90]
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.[clarification needed][91] 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.[92]
Pharmacology
Several classes of
Mechanism of action
At rest, serotonin is stored within the vesicles of presynaptic neurons. When stimulated by nerve impulses, serotonin is released as a neurotransmitter into the synapse, reversibly binding to the postsynaptic receptor to induce a nerve impulse on the postsynaptic neuron. Serotonin can also bind to auto-receptors on the presynaptic neuron to regulate the synthesis and release of serotonin. Normally serotonin is taken back into the presynaptic neuron to stop its action, then reused or broken down by monoamine oxidase.[93]
Psychedelic drugs
The
Antidepressants
Drugs that alter serotonin levels are used in treating
Certain SSRI medications have been shown to lower serotonin levels below the baseline after chronic use, despite initial increases.[99] 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.[100] The 5-HTTLPR polymorphism (l/l) causing more serotonin transporters to be formed is also found to be more resilient against depression and anxiety.[101][102]
Serotonin syndrome
Extremely high levels of serotonin can cause a condition known as
Antiemetics
Some
Other
Some serotonergic agonist drugs cause fibrosis anywhere in the body, particularly the syndrome of retroperitoneal fibrosis, as well as cardiac valve fibrosis.[108] 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),[108] the serotonergic appetite suppressant drugs (fenfluramine, chlorphentermine, and aminorex), and certain anti-Parkinsonian dopaminergic agonists, which also stimulate serotonergic 5-HT2B receptors. These include pergolide and cabergoline, but not the more dopamine-specific lisuride.[109]
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.[110]
Two independent studies published in The New England Journal of Medicine in January 2007 implicated pergolide, along with cabergoline, in causing valvular heart disease.[111][112] As a result of this, the FDA removed pergolide from the United States market in March 2007.[113] (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).[114]
Methyl-tryptamines and hallucinogens
Several plants contain serotonin together with a family of related
Comparative biology and evolution
Unicellular organisms
Serotonin is used by a variety of single-cell organisms for various purposes.
Edible plants and mushrooms
In drying
However, since serotonin is a major gastrointestinal tract modulator, it may be produced in the fruits of plants 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
Serotonin is one compound of the poison contained in
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.[122]
Root development in Arabidopsis thaliana is stimulated and modulated by serotonin – in various ways at various concentrations.[123]
Serotonin serves as a plant defense chemical against fungi. When infected with
Invertebrates
Serotonin functions as a neurotransmitter in the nervous systems of most animals.
Nematodes
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.[128] 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.[129] The released serotonin activates the muscles used for feeding, while octopamine suppresses them.[130][131] Serotonin diffuses to serotonin-sensitive neurons, which control the animal's perception of nutrient availability.
Decapods
If
In venoms
Serotonin is a common component of invertebrate venoms, salivary glands, nervous tissues, and various other tissues, across molluscs, insects, crustaceans, scorpions, various kinds of worms, and jellyfish.
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.[134][17] Some circuits in mushroom bodies are serotonergic.[135] (See specific Drosophila example below, §Dipterans.)
Acrididae
Locust swarming is initiated but not maintained by serotonin,[136] with release being triggered by tactile contact between individuals.[137] This transforms social preference from aversion to a gregarious state that enables coherent groups.[138][137][136] Learning in flies and honeybees is affected by the presence of serotonin.[139][140]
Role in insecticides
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.[141]
Hymenopterans
Dipterans
If flies are fed serotonin, they are more aggressive; flies depleted of serotonin still exhibit aggression, but they do so much less frequently.
Vertebrates
Serotonin, also referred to as 5-hydroxytryptamine (5-HT), is a neurotransmitter most known for its involvement in mood disorders in humans. It is also a widely present neuromodulator among vertebrates and invertebrates.[147] Serotonin has been found having associations with many physiological systems such as cardiovascular, thermoregulation, and behavioral functions, including: circadian rhythm, appetite, aggressive and sexual behavior, sensorimotor reactivity and learning, and pain sensitivity.[148] Serotonin's function in neurological systems along with specific behaviors among vertebrates found to be strongly associated with serotonin will be further discussed. Two relevant case studies are also mentioned regarding serotonin development involving teleost fish and mice.
In mammals, 5-HT is highly concentrated in the substantia nigra, ventral tegmental area and raphe nuclei. Lesser concentrated areas include other brain regions and the spinal cord.[147] 5-HT neurons are also shown to be highly branched, indicating that they are structurally prominent for influencing multiple areas of the CNS at the same time, although this trend is exclusive solely to mammals.[148]
5-HT system in vertebrates
Dogs / canine species
There are few studies of serotonin in dogs. One study reported serotonin values were higher at dawn than at dusk.[151] In another study, serum 5-HT levels did not seem to be associated with dogs' behavioural response to a stressful situation.[152] Urinary serotonin/creatinine ratio in bitches tended to be higher 4 weeks after surgery. In addition, serotonin was positively correlated with both cortisol and progesterone but not with testosterone after ovariohysterectomy.[153]
Teleost fish
Like non-placental vertebrates, teleost fish also possess 5-HT cells in other sections of the brain, including the basal forebrain.[149] Danio rerio (zebra fish) are a species of teleost fish often used for studying serotonin within the brain. Despite much being unknown about serotonergic systems in vertebrates, the importance in moderating stress and social interaction is known.[154] It is hypothesized that AVT and CRF cooperate with serotonin in the hypothalamic-pituitary-interrenal axis.[149] These neuropeptides influence the plasticity of the teleost, affecting its ability to change and respond to its environment. Subordinate fish in social settings show a drastic increase in 5-HT concentrations.[154] High levels of 5-HT long term influence the inhibition of aggression in subordinate fish.[154]
Mice
Researchers at the Department of Pharmacology and Medical Chemistry used serotonergic drugs on male mice to study the effects of selected drugs on their behavior.[155] Mice in isolation exhibit increased levels of agonistic behavior towards one another. Results found that serotonergic drugs reduce aggression in isolated mice while simultaneously increasing social interaction.[155] Each of the treatments use a different mechanism for targeting aggression, but ultimately all have the same outcome. While the study shows that serotonergic drugs successfully target serotonin receptors, it does not show specifics of the mechanisms that affect behavior, as all types of drugs tended to reduce aggression in isolated male mice.[155] Aggressive mice kept out of isolation may respond differently to changes in serotonin reuptake.
Behavior
Like in humans, serotonin is extremely involved in regulating behavior in most other vertebrates. This includes not only response and social behaviors, but also influencing mood. Defects in serotonin pathways can lead to intense variations in mood, as well as symptoms of mood disorders, which can be present in more than just humans.
Social interaction
One of the most researched aspects of social interaction in which serotonin is involved is aggression. Aggression is regulated by the 5-HT system, as serotonin levels can both induce or inhibit aggressive behaviors, as seen in mice (see section on Mice) and crabs.[155] While this is widely accepted, it is unknown if serotonin interacts directly or indirectly with parts of the brain influencing aggression and other behaviors.[147] Studies of serotonin levels show that they drastically increase and decrease during social interactions, and they generally correlate with inhibiting or inciting aggressive behavior.[156] The exact mechanism of serotonin influencing social behaviors is unknown, as pathways in the 5-HT system in various vertebrates can differ greatly.[147]
Response to stimuli
Serotonin is important in environmental response pathways, along with other neurotransmitters.[157] Specifically, it has been found to be involved in auditory processing in social settings, as primary sensory systems are connected to social interactions.[158] Serotonin is found in the IC structure of the midbrain, which processes specie specific and non-specific social interactions and vocalizations.[158] It also receives acoustic projections that convey signals to auditory processing regions.[158] Research has proposed that serotonin shapes the auditory information being received by the IC and therefore is influential in the responses to auditory stimuli.[158] This can influence how an organism responds to the sounds of predatory or other impactful species in their environment, as serotonin uptake can influence aggression and/or social interaction.
Mood
We can describe mood not as specific to an emotional status, but as associated with a relatively long-lasting emotional state. Serotonin's association with mood is most known for various forms of depression and bipolar disorders in humans.
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.[31] Serotonin is necessary for normal nematode male mating behavior,[159] and the inclination to leave food to search for a mate.[160] 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,[161] which control long-term adaption.
In the
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.[165][166]
Serotonin is known to regulate aging, learning and memory. The first evidence comes from the study of longevity in
Biochemical mechanisms
Biosynthesis
In animals and 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:
Serotonin can be synthesized from tryptophan in the lab using
Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system, because it does not cross the
Analytical chemistry
History and etymology
It had been known to physiologists for over a century that a vasoconstrictor material appears in serum when blood was allowed to clot.[172] 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".[173][174] 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.[175]
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.
See also
Notes
- ^ References for the functions of these receptors are available on the wikipedia pages for the specific receptor in question
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p. 231,
The change in the number of several potential neurotransmitters ... such as serotonin... may play an important role in remodeling the CNS during phase change (26, 56, 80).
p. 233,
In the locust S. gregaria, the amount of serotonin in the thoracic ganglia was positively correlated with the extent of gregarious behavior induced by different periods of crowding. A series of pharmacological and behavioral experiments demonstrated that serotonin plays a key role in inducing initial behavioral gregarization (2, 80). However, serotonin is not responsible for maintaining gregarious behavior because its amount in long-term gregarious locusts is less than half that in long-term solitarious locusts (80). In L. migratoria, the injection of serotonin can also slightly initiate gregarious behavior, but serotonin when accompanying crowding treatment induced more solitarious-like behavior than did serotonin injection alone (48). Significant differences in serotonin levels were not found in brain tissues between the two phases of L. migratoria. A recent report by Tanaka & Nishide (97) measured attraction/avoidance behavior in S. gregaria after single and multiple injections of serotonin at different concentrations. Serotonin had only a short-term effect on the level of some locomotor activities and was not involved in the control of gregarious behavior (97). In addition, it is not clear how the neurotransmitter influences this unique behavior, because a binary logistic regression model used in these studies for the behavioral assay focused mostly on only one behavioral parameter representing an overall phase state. Obviously, behavioral phase change might involve alternative regulatory mechanisms in different locust species. Therefore, these studies demonstrate that CNS regulatory mechanisms governing initiation and maintenance of phase change are species specific and involve the interactions between these neurotransmitters.
Given the key roles of aminergic signaling, what are the downstream pathways involved in the establishment of long-term memory? Ott et al. (63) investigated the role of [] protein kinase[] in the phase change in S. gregaria: ... cAMP-dependent protein kinase A (PKA). Through use of pharmacological and RNAi intervention, these authors have demonstrated that PKA... has a critical role in modulating the propensity of locusts to acquire and express gregarious behavior. ... Unfortunately, although a correlation between serotonin and PKA was hypothesized, direct evidence was not provided. - ^ S2CID 52843907. p. 20:
...gregarization is evoked by... tactile stimulation... Tactile stimuli trigger the increase of biogenic amines, particularly serotonin, in the locust nervous system (1, 116); these amines play critical roles in the neurophysiology of locust behavioral phase change.
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Table 1 The respective potential peaks for various electroactive biomolecules that are produced or consumed by microbes reported in the literaturea ... Serotonin | Indium tin oxide | +0.67 | 66
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Further reading
- Gutknecht L, Jacob C, Strobel A, Kriegebaum C, Müller J, Zeng Y, et al. (June 2007). "Tryptophan hydroxylase-2 gene variation influences personality traits and disorders related to emotional dysregulation". The International Journal of Neuropsychopharmacology. 10 (3): 309–320. PMID 17176492.
External links
- 5-Hydroxytryptamine MS Spectrum
- Serotonin bound to proteins in the PDB
- PsychoTropicalResearch Extensive reviews on serotonergic drugs and Serotonin Syndrome.
- Molecule of the Month: Serotonin at University of Bristol
- 60-Second Psych: No Fair! My Serotonin Level Is Low, Scientific American
- Serotonin Test Interpretation on ClinLab Navigator.