Serotonin

Diet
Both serotonin and its precursor tryptophan are amino acids. Our diet cannot feed our brain the serotonin it needs because the blood-brain barrier (BBB) will block it from entering. Even tryptophan cannot cross BBB. Low serotonin is linked with depression.
http://bebrainfit.com/serotonin-foods-mood-brain/


Sources

1. Serotonin is released into the space between neurons, and diffuses over a relatively wide gap (>20 µm) to activate 5-HT receptors located on the dendrites, cell bodies and presynaptic terminals of adjacent neurons.
2. Serotonin in mammals is made by two different tryptophan hydroxylases: TPH1 produces serotonin in the pineal gland and the enterochromaffin cells, while TPH2 produces it in the raphe nuclei and in the myenteric plexus. 
3. Genetically altered mice lacking TPH1 develop progressive loss of heart strength early on. They have pale skin and breathing difficulties, are easily tired, and eventually die of heart failure. Genetically altered mice that lack TPH2 are normal when they are born. However, after three days, they appear to be smaller and weaker, and have softer skin than their siblings. In a purebred strain, 50% of the mutants died during the first four weeks, but in a mixed strain, 90% survived. Normally, the mother weans the litter after three weeks, but the mutant animals needed five weeks. After that, they caught up in growth and had normal mortality rates. Subtle changes in the autonomic nervous system are present, but the most obvious difference from normal mice is the increased aggressiveness and impairment in maternal care of young. Despite the blood–brain barrier, the loss of serotonin production in the brain is partially compensated by intestinal serotonin. The behavioural changes become greatly enhanced if one crosses TPH1- with TPH2-lacking mice and gets animals that lack TPH entirely.
4. 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 disgorge serotonin, where it serves as a vasoconstrictor and helps to regulate hemostasis and blood clotting. 
5. Serotonin also is a growth factor for some types of cells, which may give it a role in wound healing.
6. Approximately 90% of the human body's total serotonin is located in the enterochromaffin cells in the alimentary canal (gut), where it is used to regulate intestinal movements. 
7. The remainder is synthesized in serotonergic neurons of the CNS, where it has various functions. These include the regulation of mood, appetite, and sleep. 
8. Modulation of serotonin at synapses is thought to be a major action of several classes of pharmacological antidepressants.

Actions

1. Serotonin is known to regulate aging, learning and memory. 
2. Serotonin also has some cognitive functions, including memory and learning. 
3. Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS) of animals and humans. It is popularly thought to be a contributor to feelings of well-being and happiness.
4. In humans, serotonin levels are affected by diet. An increase in the ratio of tryptophan to phenylalanine and leucine will increase serotonin levels. Fruits with a good ratio include dates, papayas and bananas. Research also suggests eating a diet rich in carbohydrates and low in protein will increase serotonin by secreting insulin, which helps in amino acid competition. However, increasing insulin for a long period may trigger the onset of insulin resistance, obesity, type 2 diabetes, and lower serotonin levels. Muscles use many of the amino acids except tryptophan, allowing more muscular individuals to produce more serotonin.
5. Serotonin functions as a neurotransmitter in the nervous systems of simple, as well as complex, animals.
6. Serotonin is a neurotransmitter and is found in all bilateral animals, where it mediates gut movements and the animals' perceptions of resource availability. 
7. Serotonin is found in animals, fungi and plants. Serotonin is present in insect venoms and plant spines and serves to cause pain, which is a side effect of serotonin injection. 
8. Serotonin is produced by pathogenic amoebae, and its effect on the gut causes diarrhea. 
9. Its widespread presence in many seeds and fruits may serve to stimulate the digestive tract into expelling the seeds.
10. Serotonin is mainly metabolized to 5-HIAA, chiefly by the liver. Metabolism involves first oxidation by monoamine oxidase to the corresponding aldehyde. This is followed by oxidation by aldehyde dehydrogenase to 5-HIAA, the indole acetic acid derivative. The latter is then excreted by the kidneys. 
11. One type of tumor, called carcinoid, sometimes secretes large amounts of serotonin into the blood, which causes various forms of the carcinoid syndrome of flushing, diarrhea, and heart problems. 
12. Because of serotonin's growth-promoting effect on cardiac myocytes, persons with serotonin-secreting carcinoid may suffer a right heart (tricuspid) valve disease syndrome, caused by proliferation of myocytes onto the valve.
13. Since serotonin is an indicator of bleeding, a sudden large increase in peripheral levels causes pain. The reason wasps and deathstalker scorpions have serotonin in their venom may be to increase the pain of their stings on large animals, and also to cause lethal vasoconstriction in smaller prey.
14. Some serotonergic agonist drugs also cause fibrosis anywhere in the body, particularly the syndrome of retroperitoneal fibrosis, as well as cardiac valve fibrosis. In the past, three groups of serotonergic drugs have been epidemiologically linked with these syndromes. They are the serotonergic vasoconstrictive antimigraine drugs (ergotamine and methysergide), the serotonergic appetite suppressant drugs (fenfluramine, chlorphentermine, and aminorex), and certain anti-Parkinsonian dopaminergic agonists, which also stimulate serotonergic 5-HT2B receptors. 
15. 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. 
16. 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.
17. In humans, though insulin regulates blood sugar and IGF regulates growth, serotonin controls the release of both hormones, so serotonin suppresses insulin release from the beta-cells in the pancreas, and exposure to SSRIs reduces fetal growth. 
18. Human serotonin can also act as a growth factor directly. Liver damage increases cellular expression of 5-HT2A and 5-HT2B receptors. Serotonin present in the blood then stimulates cellular growth to repair liver damage. 5HT2B receptors also activate osteocytes, which build up bone. However, serotonin also inhibits osteoblasts, through 5-HT1B receptors.
19. 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 Htr1b receptors, it negatively regulates bone mass, while it does so positively through Htr2b and Htr2c. 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.
20. These studies have opened a new area of research in bone metabolism that can be potentially harnessed to treat bone mass disorders.
21. In humans, defective signaling of serotonin in the brain may be the root cause of sudden infant death syndrome (SIDS). 
22. Scientists from the European Molecular Biology Laboratory in Monterotondo, Italy genetically modified lab mice to produce low levels of the neurotransmitter serotonin. The results showed the mice suffered drops in heart rate and other symptoms of SIDS, and many of the animals died at an early age. Researchers now believe low levels of serotonin in the animals' brainstems, which control heartbeat and breathing, may have caused sudden death, they said in the July 4, 2008 issue of Science.
23. If neurons that make serotonin — serotonergic neurons — are abnormal in infants, there is a risk of sudden infant death syndrome (SIDS).
24. Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system, because it does not cross the blood–brain barrier (BBB). However, tryptophan and its metabolite 5-hydroxytryptophan (5-HTP), from which serotonin is synthesized, can and do cross the BBB. These agents are available as dietary supplements, and may be effective serotonergic agents. 
25. One product of serotonin breakdown is 5-hydroxyindoleacetic acid (5-HIAA), which is excreted in the urine. 
26. 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.
27. 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 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 neuron-specific isoform.
28. Serotonin can also signal through a nonreceptor mechanism called serotonylation, in which serotonin modifies proteins. This process underlies serotonin 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. A similar process underlies the pancreatic release of insulin. 
29. 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.
30. 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. 
31. Various agents can inhibit 5-HT reuptake, including MDMA (ecstasy), amphetamine, cocaine, dextromethorphan (an antitussive), tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). 
32. Interestingly, a 2006 study conducted by the University of Washington suggested a newly discovered monoamine transporter, known as PMAT, may account for "a significant percentage of 5-HT clearance". 
33. Contrasting with the high-affinity SERT, the PMAT has been identified as a low-affinity transporter, with an apparent Km of 114 micromoles/l for serotonin; approximately 230 times higher than that of SERT. 
34. 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." 
35. The study also suggests some SSRIs, such as fluoxetine and sertraline, 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. 
36. 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 Km values even higher than that of 5-HT (330–15,000 μmoles/L).
37. 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. 
38. With the exception of the 5-HT3 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.
39. 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.
40. The psychedelic drugs psilocin/psilocybin, DMT, mescaline, and LSD are agonists, primarily at 5HT2A/2C receptors. The empathogen-entactogen MDMA releases serotonin from synaptic vesicles of neurons.
41. Drugs which alter serotonin levels are used in depression, generalized anxiety disorder and social phobia. 
42. Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of monoamine neurotransmitters (including serotonin), and therefore increase concentrations of the neurotransmitter in the brain. 
43. 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. 
44. Some drugs inhibit the reuptake of serotonin, making it stay in the synaptic cleft longer. 
45. The tricyclic antidepressants (TCAs) inhibit the reuptake of both serotonin and norepinephrine. 
46. The newer selective serotonin reuptake inhibitors (SSRIs) have fewer side effects and fewer interactions with other drugs.

http://upload.wikimedia.org/wikipedia/commons/1/1c/Serotonin_biosynthesis.svg
http://upload.wikimedia.org/wikipedia/en/8/88/Dopamineseratonin.png
http://en.wikipedia.org/wiki/Serotonin