Serotonin is 5-hydroxytryptamine [5-HT]).
It is formed from the decarboxylation and hydroxylation of tryptophan.
Serotonin is then stored in vesicles and released into the synaptic cleft when stimulated.
Serotonin is metabolized by monoamine oxidase-A (MAO-A) into 5-hydroxyindoleacetic acid.
Serotonin can bind to at least 7 families of 5-HT receptors.
5HT-2A receptors are the most important serotonin receptors involved in SS.
A monoamine neurotransmitter.
Biochemically derived from tryptophan.
Synthesized from the amino acid L-tryptophan by a short metabolic pathway consisting of two enzymes: tryptophan hydroxylase and amino acid.
Serotonin acts both peripherally and centrally.
Peripheral serotonin is produced primarily in the enterochromaffin cells of the gastrointestinal tract.
Mechanical and chemical stimuli release serotonin from enteric neurons and mucosal enterochromaffin cells.
Serotonin initiates motor reflexes and visceral sensation.
Serotonin stimulate vasoconstriction, uterine contraction, bronchoconstriction, GI motility, and platelet aggregation.
Centrally serotonin is located in the midline raphe nuclei of the brainstem from the midbrain to the medulla.
Serotonin functions to inhibit excitatory neurotransmission and to modulate wakefulness, attention, affective behavior of anxiety and depression, sexual behavior, appetite, thermoregulation, motor tone, migraine, emesis, nociception, and aggression.
Primarily found in the gastrointestinal (GI) tract, platelets, and in the central nervous system (CNS).
A contributor to feelings of well-being and happiness.
Approximately 90% is located in the enterochromaffin cells in the alimentary canal .
Peripheral serotonin is produced primarily in the enterochromaffin cells of the gastrointestinal tract.
Regulates intestinal motility.
Serotonin acts both peripherally and centrally.
The remainder is synthesized in serotonergic neurons of the CNS.
CNS functions include the regulation of mood, appetite, sleep, and some cognitive, learning, and memory processes.
A number of classes of antidepressants alter serotonin at synapses and provides their mechanism of action.
Serotonin secreted from the enterochromaffin cells enter the blood stream and is actively taken up and stored by platelets.
Upon binding to a clot, platelets disgorge serotonin, where it serves as a vasoconstrictor and helps to regulate hemostasis and blood clotting.
Serotonin stimulates vasoconstriction, uterine contraction, bronchoconstriction, GI motility, and platelet aggregation.
Serotonin functions to inhibit excitatory neurotransmission and to modulate wakefulness, attention, affective behavior of anxiety and depression, sexual behavior, appetite, thermoregulation, motor tone, migraine, emesis, nociception, and aggression.
Serotonin also is a growth factor that may give it a role in wound healing.
Mainly metabolized to 5-HIAA by the liver involving initial oxidation by monoamine oxidase to the corresponding aldehyde, and followed by oxidation by aldehyde dehydrogenase to 5-HIAA, the indole acetic acid derivative.
5-HIAA is excreted by the kidneys.
Carcinoid tumors secrete large amounts of serotonin into the blood, which causes various symptoms of the carcinoid syndrome of flushing, diarrhea, and heart problems.
Serotonin growth-promoting effects on cardiac myocytes in the carcinoid syndrome cause a right heart
valve disease syndrome, caused by proliferation of myocytes onto the valve.
Involved in numerous physiologic functions, such as appetite, sleep, sexuality, irritability and pain.
Culture studies have shown stimulation of subendocardial cell proliferation mediated by serotonin receptors and animal studies reveal long-term treatment with high doses of this agent form carcinoid like plaques on cardiac valves.
Serotonin is released when consuming food and activates 5-HT2C receptors on dopamine-producing cells, so that dopamine release is stopped and appetite is decreased.
Levels are affected by diet.
An increase in the ratio of tryptophan to phenylalanine and leucine increase serotonin levels.
Foods with a lower ratio inhibit the production of serotonin, and include whole wheat and rye bread.
Fruits such as dates, papayas and bananas have a good ratio.
Drugs which block 5-HT2C receptors prevent the ability to shut off appetite, and are associated with weight gain.
Hippocampus 5-HT2C receptor expression is diurnal, as is serotonin release in the ventromedial nucleus, and is characterized by a morning peak when the motivation to eat is strongest.
If irritants are present in the food, the Enterochromaffin cells release more serotonin when irritants are present in food, to cause diarrhea to rid the intestine of the noxious substances.
When serotonin is released in the blood faster than the platelets can absorb it, levels of free serotonin increase in the blood.
Serotonin inactivated 5HT3 receptors in the chemoreceptor trigger zone stimulate vomiting.
The enterochromaffin cells react to bad food, irradiation and cancer chemotherapy.
Drugs that block 5HT3 are very effective in controlling the nausea and vomiting produced by cancer treatment.
Levels of 5-HT1A receptor activation in the brain show negative correlation with aggression.
A mutation in the gene that codes for the 5-HT2A receptor may double the risk of suicide.
Most of the brain serotonin is not degraded after use.
After use serotonin is collected at the cell surfaces of serotonergic neurons by serotonin transporters.
About 10% of variability in anxiety related personality qualities is dependent on serotonin transporter numbers and function.
Serotonin is known to play a role in regulating aging, learning and memory, and levels fall with late phase of aging.
Increased blood levels a predictor of low bone density, by inhibiting osteoblasts.
Suppresses insulin release from the beta cells in the pancreas.
When platelets bind in damaged tissue, serotonin is released and acts as a vasoconstrictor to stop bleeding, and also acts as a growth factor to aid healing.
Some serotonergic agonist drugs cause fibrosis such as the syndrome of retroperitoneal fibrosis, and cardiac valve fibrosis.
Serotonin can interact with receptors on fibroblasts and likley leads to valvular fibrosis seen in ling standing carcinoid syndrome.
Serotonin may cause fibrosis of the bowel, known as mesenteric fibrosis, and can lead to bowel obstruction.
Three groups of serotonergic drugs have been linked with these syndromes: 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 pergolide and cabergoline.
Defective signaling of serotonin in the brain may be related to the sudden infant death.
Patients with depression have decreased levels of the p11 protein, which is related to serotonin transmission within the brain.
Serotonin is made from tryptophan, is thought to regulate anxiety and improve mood.
The neurons of the raphe nuclei are the principal source of 5-HT release in the brain, and there are 7 or 8 raphe nuclei located along the midline of the brainstem, and centered around the reticular formation.
The level of serotonin within the brain has a major affect on our emotions, thinking and behavior.
Anti depressants modify the amount of serotonin within the brain.
It’s believed that serotonin plays a part in the forming of mental illness.
The TPH2 gene is a key part in controlling serotonin levels.
People who had a less functional short allele on a certain area of the serotonin gene have a more difficult time recovering from trauma compared to those with long alleles.
TPH2 is involved in the development of manic depression and depression.
Axons from the neurons of the raphe nuclei form a neurotransmitter system?
This neurotransmitter system reaches extensively in the central nervous system, with axons of neurons in the lower raphe nuclei terminating in the cerebellum and spinal cord, and those of the higher nuclei spread out in the entire brain.
As serotonin is released into the space between neurons, it diffuses to activate 5-HT receptors located on the dendrites, cell bodies and presynaptic terminals of adjacent neurons.
The 5-HT receptors for serotonin, are located on the cell membrane of nerve cells and mediate its effects.
Serotonergic action is terminated by the uptake of 5-HT from the synapse, and is accomplished through the specific monoamine transporter for 5-HT, SERT, on the presynaptic neuron.
Drugs that can inhibit 5-HT reuptake, include: amphetamine, cocaine, dextromethorphan, ecstasy, tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs).
Another monoamine transporter, PMAT, may be an additional agent for 5-HT clearance, and is not inhibited by present drugs.
Taken orally it does not pass into the serotonergic pathways of the central nervous system, because it does not cross the blood–brain barrier.
Tryptophan and its metabolite 5-hydroxytryptophan (5-HTP) can cross the blood–brain barrier and are the precursors to serotonin.
Tryptophan and its metabolite 5-hydroxytryptophan (5-HTP) are available as dietary supplements, and may be effective serotonergic agents.
Drugs that target the 5-HT system include: some antidepressants, antipsychotics, anxiolytics, antiemetics, antimigraine drugs, as well as the psychedelic drugs.
Monoamine oxidase inhibitors prevent the breakdown of monoamine neurotransmitters including serotonin.
Monoamine oxidase inhibitors increase concentrations of the neurotransmitter serotonin in the brain.
Some drugs can inhibit the reuptake of serotonin, making it stay in the synaptic cleft longer.
Certain SSRI medications can lower serotonin levels below the baseline after chronic use, despite initial increases, and the benefit of SSRIs may decrease in selected patients after a long-term treatment.
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.
Extremely high levels can cause a condition known as serotonin syndrome, with toxic and potentially fatal effects.
Such toxic levels are not reached through an overdose of a single antidepressant drug, but require a combination of serotonergic agents, such as an SSRI with an MAOI.
The intensity of the symptoms of serotonin syndrome vary over a wide spectrum of symptoms.
Some 5-HT3 antagonists, such as ondansetron, granisetron, are important antiemetic agents in treating chemotherapy induced and postoperative nausea and vomiting.
Found in mushrooms, fruits and vegetables.
Serotonin and tryptophan found in chocolate.
The highest serotonin content found in chocolate with 85% cocoa, and the highest tryptophan content found in 70-85% cocoa.
Since serotonin does not cross the blood–brain barrier, ingesting serotonin in the diet has no effect on brain serotonin.