A European Informational Website
learn more
]] Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS) and enterochromaffin cells in the gastrointestinal tract of animals including humans. Serotonin is also found in many mushrooms and plants, including fruits and vegetables.
In the central nervous system, serotonin is believed to play an important role in the regulation of anger, aggression, body temperature, mood, sleep, vomiting, sexuality, and appetite. Low levels of serotonin may be associated with several disorders, namely increase in aggressive and angry behaviors, clinical depression, obsessive-compulsive disorder (OCD), migraine, irritable bowel syndrome, tinnitus, fibromyalgia, bipolar disorder, anxiety disorders and intense religious experiences[1]. If neurons of the brainstem that make serotonin—serotonergic neurons—are abnormal, there is a risk of sudden infant death syndrome (SIDS).[2][3]
Isolated and named in 1948 by Maurice M. Rapport, Arda Green, and Irvine Page,[4] the name "serotonin" is something of a misnomer and reflects the circumstances of the compound's discovery. It was initially identified as a vasoconstrictor substance in blood serum – hence serotonin, a serum agent affecting vascular tone. This agent was later chemically identified as 5-hydroxytryptamine (5-HT) by Rapport, and, as the broad range of physiological roles were elucidated, 5-HT became the preferred name in the pharmacological field.
Serotonin is synthesized extensively in the human gastrointestinal tract (about 90%),<sup>[4]</sup> and the major storage place is platelets in the blood stream.
In the body, serotonin is synthesized from the amino acid tryptophan by a short metabolic pathway consisting of two enzymes – tryptophan hydroxylase (TPH) and amino acid decarboxylase (DDC). The TPH mediated reaction is the rate limiting step in the pathway. TPH has been shown to exist in two forms; TPH1, found in several tissues and TPH2, which is a brain specific isoform. There is evidence that genetic polymorphisms in both these subtypes influence susceptibility to anxiety and depression (Nash et al 2005; Zhang et al 2005). There is also evidence that ovarian hormones can affect the expression of TPH in various species, suggesting a possible mechanism for postpartum depression and premenstrual stress syndrome (Hiroi et al 2006). The gut secretes over 95% of the body's serotonin.[5] <br />
<br style="clear: both;" />
Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system because it does not cross the blood-brain barrier. However, tryptophan and its metabolite 5-Hydroxytryptophan (5-HTP), from which serotonin is synthesized, can and 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.
The neurons of the Raphe nuclei are the principal source of 5-HT release in the brain.[6] The raphe nuclei are neurons grouped into about nine pairs and distributed along the entire length of the brainstem, centered around the reticular formation[7]. 5-HT is thought to be released from serotonergic varicosities into the extra neuronal space, in other words from swellings (varicosities) along the axon, rather than from synaptic terminal buttons (in the manner of classical neurotransmission). From here it is free to diffuse over a relatively large region of space (>20µm) and activate 5-HT receptors located on the dendrites, cell bodies and presynaptic terminals of adjacent neurons.
Serotonergic action is terminated primarily via uptake of 5-HT from the synapse. This is through the specific monoamine transporter for 5-HT, 5-HT reuptake transporter, on the presynaptic neuron. Various agents can inhibit 5-HT reuptake including MDMA (ecstasy), amphetamine, cocaine, dextromethorphan, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs).
Recent research suggests that serotonin plays an important role in liver regeneration and acts as a mitogen (induces cell division) throughout the body.[8]
The pharmacology of 5-HT is extremely complex, with its actions being mediated by a large and diverse range of 5-HT receptors. At least seven different receptor "families" are known to exist, each located in different parts of the body and triggering different responses. As with all neurotransmitters, the effects of 5-HT on the human mood and state of mind, and its role in consciousness, are very difficult to ascertain.
In the field of neurochemistry, 5-HT receptors are receptors for the neurotransmitter and peripheral signal mediator serotonin (5-HT). 5-HT receptors 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. With the exception of the 5-HT<sub>3</sub> receptor, a ligand gated ion channel, all other 5-HT receptors are G protein coupled seven transmembrane (or heptahelical) receptors that activate an intracellular second messenger cascade.
There exist many drugs that innately modulate the 5-HT system in such a way to produce alterations in perception, emotional response, and thought process. These include Psilocin/Psilocybin, DMT, Mescaline, LSD, MDMA (ecstasy), and Ibogaine. These and many more have been described in the books TiHKAL and PiHKAL by Alexander Shulgin.
Various drugs are used to modulate the 5-HT system including some antidepressants, anxiolytics, antiemetics, and triptans.
A variety of psychiatric medications affect serotonin levels, including the monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), atypical antipsychotics, the selective serotonin reuptake inhibitors (SSRIs), and amphetamines. Recreational substances such as MDA, MDMA, and MDEA also affect serotonin levels. Research by GW Pharma in the UK has shown that cannabis modulates serotonin levels through g-proteins, also resulting in an anti-nauseant effect.
The 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 crisis triggered by foods with high tyramine-content and certain drugs.
Some drugs inhibit this re-uptake of serotonin, again making it stay in the synapse longer. The tricyclic antidepressants inhibit the re-uptake of both serotonin and norepinephrine. The newer Selective Serotonin Re-uptake Inhibitors (SSRIs) have fewer (though still numerous) side effects and fewer interactions with other drugs.
Recent research conducted at Rockefeller University shows that in both patients who suffer from depression and in mice that model that disease, levels of the p11 protein are decreased. This protein is related to serotonin transmission within the brain.[9]
5-HT<sub>3</sub> 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 treatment of post-operative nausea and vomiting. Applications to the treatment of depression and other mental and psychological conditions have also been investigated with some positive results.
Extremely high levels of serotonin can have toxic and potentially fatal effects, causing a condition known as serotonin syndrome. In practice, such toxic levels are essentially impossible to reach through an overdose of a single anti-depressant drug, but require a combination of serotonergic agents, such as an SSRI with an MAOI.[10] The intensity of the symptoms of serotonin syndrome vary over a wide spectrum, and the milder forms are seen even at non-toxic levels.[11] For example, recreational doses of MDMA (ecstasy) will generally cause such symptoms but only rarely lead to true toxicity.
Serotonin is found in mushrooms and plants, including fruits and vegetables. The highest values of 25 - 400 mg/kg have been found in nuts of the walnut (Juglans) and hickory (Carya) genus. Serotonin concentrations of 3 - 30 mg/kg have been found in plantain, pineapple, banana, kiwi, plums, and tomatoes. Moderate levels from 0.1 - 3 mg/kg have been found in a wide range of tested vegetables.[12] Serotonin is one compound of the poison contained in the stinging hairs of the stinging nettle (Urtica dioica). Several plants contain serotonin together with a family of related tryptamines that are methylated at the amino (NH<sub>2</sub>) and hydroxy (OH) groups, are ''N''-oxides, or miss the OH group. Example are plants from the Anadenanthera genus that are used in the hallucinogenic yopo snuff.
</span></span></span>