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5-hydroxytryptamine is an indole derivative, referred to as 5-HT, with a chemical formula of C10H12N2O and a molecular weight of 176.22. 5-hydroxytryptamine was first discovered in serum, also known as serotonin. It is widely present in mammalian tissues, especially in the cerebral cortex and synapses. It is also an inhibitory neurotransmitter. 5-hydroxytryptamine can react with acid to form crystalline salts. The melting point of its hydrochloride is 167~168°C; the melting point of its picrate is 185~189°C. The concentration of 5-hydroxytryptamine in brain tissue is high, and it is an important substance for regulating neural activity. Some body tissues can release 5-hydroxytryptamine when affected by certain drugs. For example, one reserpine molecule can cause the affected tissue to release hundreds of 5-hydroxytryptamine molecules, thus producing a series of physiological effects of reserpine. As a self-active substance, about 90% is synthesized and distributed in enterochromaffin cells, and is usually stored in cell granules together with substances such as ATP. Under the action of stimuli, 5-HT is released from the granules, diffuses into the blood, and is taken up and stored by platelets, accounting for about 8% of the body. As a neurotransmitter, 5-HT is mainly distributed in the pineal gland and hypothalamus, and may be involved in the regulation of physiological functions such as pain, sleep and body temperature. Abnormal 5-HT content and function in the central nervous system may be related to the onset of various diseases such as mental illness and migraine. 5-HT can only take effect through the mediation of corresponding receptors. The classification of 5-HT receptors is complex, and 7 5-HT receptor subtypes have been discovered. 5-HT can have different pharmacological effects by stimulating different 5-HT receptor subtypes.
Figure 1. Serotonin is synthesized in EC cells. (Sources: Kanova M, et al. 2021)
Serotonin is an amine neurotransmitter in the same category as dopamine and adrenaline. It is synthesized by the hydroxylation of tryptophan, one of the essential amino acids for the human body. This process is completed in the small intestinal epithelium, so it is clear that the raw material used by the small intestinal epithelium comes from tryptophan in the diet. Serotonin, a messenger between nerve cells, is mainly found in the digestive system and a small amount in blood platelets. It is secreted and stored by enterochromaffin cells, and when activated is released into the blood (called serotonin), and some is temporarily stored in the blood by platelets. Because the gut can secrete neurotransmitters that affect the brain, the digestion and metabolic pathways of the food we eat are far more complex than the energy and nutrient supply generally believed. The intestinal chromaffin cells are located in the intestinal epithelial cells, so they are also the first line of barrier between the intestine and food. Therefore, after serotonin enters the blood from the intestinal epithelium, it will act directly on the enteric nervous system through paracrine effects or act distally on the central nervous system through the endocrine system. Because there are neurons in the gut and the central nervous system that can receive serotonin, it is like having a receiving station for this type of messenger. And these receiving stations are different (different subtypes of receptors), which means that they all accept serotonin, but they perform different functions, so serotonin actually has very complex functions.
The role of serotonin in the central nervous system is very important. This is the emotion and perception that the brain can directly feel: it regulates pain, mental emotions, sleep, body temperature, sexual behavior, and pituitary endocrine. Because the reduction of serotonin (it may be production or secretion) is related to emotional depression and depression, the mechanism of some antidepressants is to reduce the degradation of serotonin, thereby temporarily increasing the concentration of serotonin in the body; but this is precisely why depression cannot be cured by drugs, because it does not solve the essential problem. In summary, serotonin is a messenger mainly secreted by the gastrointestinal epithelium. This messenger can not only directly act on the nerve plexus of the gastrointestinal tract, but also enter the blood and act in the central nervous system. As a result, the stimulation of the gastrointestinal tract (whether it is eating itself or the balance of nutrients) will be reflected in the health of the gastrointestinal tract and the perception of the brain. This is one of the operating mechanisms of the classic brain-gut axis. High or low levels of serotonin can also cause health problems. High levels can lead to serotonin syndrome, a life-threatening condition. Low levels can cause depression. Many health problems are linked to low levels of serotonin in the brain. There are many reasons for low serotonin levels, including stress, lack of sleep, poor diet and lack of exercise. When it drops below the required level, people have problems concentrating, which indirectly affects their ability to plan and organize. This condition is often accompanied by feelings of stress and boredom, and if serotonin levels drop further, it can lead to depression.
5-Hydroxytryptamine
5-HT
Enteramine
Thrombocytin
Hydroxytryptamine
References
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Paroxetine binding and activation of phosphofructokinase implicates energy metabolism in antidepressant mode of action
JOURNAL OF PSYCHIATRIC RESEARCH
Authors: Park, Dong Ik; Novak, Bozidar; Yan, Yu; Kaya, Melahat Ezgi; Turck, Christoph W.
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CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS
Authors: Thawani, Rajat; Nannapaneni, Srikant; Kumar, Vivek; Oo, Phone; Simon, Michael; Huang, Anna; Malhotra, Ishan; Xu, Yiqing
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