Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter.
It is found extensively in the gastrointestinal tract of animals, and about 80 to 90 percent of the human body's total serotonin is located in the enterochromaffin cells in the gut, where it is used to regulate intestinal movements. The remainder is synthesized in serotonergic neurons in the central nervous system (CNS) where it has various functions, including control of appetite, mood and anger.
Localization of Serotonin producing cells
The highest concentrations than 5-HT are found in three various bodily sites: in the cells enterochromaffin that contain approximately 90% of the amount total of 5-HT present in the organism, these are cells derived from the neural crest, similar to those of the medullary one of the adrenal gland, and stirred to the mucosal cells, mainly in the stomach and in the tenuous intestine.
Another site is the blood: the 5-HT present in it is elevated concentrations in the platelets, they accumulate than it from the plasma through a system of active transport they release and it later on aggregation that verification in the sites of damage for tissue; the last site is the central nervous system, where the 5-HT is an important emitter of the SNC
and present in elevated concentrations in specific areas of the mesencephalon.
The bodies of serotonergic neurons are located on the midline of the brainstem at the level of the bulb, midbrain and the bridge, concentrated in the raphe nuclei.
The raphe nuclei of give rise to a homogeneous group of neurons that project their axons to all major areas of the central nervous system: cortex, thalamus, amygdala, hippocampus, nuclei of the base, the nucleus accumbens, cerebellum, spinal cord. Serotonergic fibers projecting to the posterior horn of the spinal cord, especially to the plates I and II and to the spinal trigeminal nucleus, indicating an involvement of the serotonergic system in pain control.
Enterochromaffin (EC) cells (Kulchitsky cells) are a type of enteroendocrine cell occurring in the epithelia lining the lumen of the digestive tract and the respiratory tract.
They produce and contain about 90% of the body's store of serotonin (5-HT).
In the gastrointestinal tract, 5-HT is important in response to chemical, mechanical or pathological stimuli in the lumen. It activates both secretory and peristaltic reflexes, and activates vagal afferents (via 5-HT3 receptors) that signal to the brain (important in the generation of nausea). Ondansetron is an antagonist of the 5-HT3 receptor and is an effective anti-emetic.
Embryologically, the enterochromaffin cells are derived from the neural crest, a group of migratory cells derived from the ectoderm.
They are called "entero" meaning related to the gut and "chromaffin" because of a chromium salt reaction that they share with chromaffin cells of the adrenal medulla (adrenal glands).
SYNTHESIS, METABOLISM AND INVESCICLATION OF SEROTONIN (5-HT)
Neosynthetized serotonin is concentrated in synaptic vesicles by a specific transporter (SERT), the release is for exocytosis physiological Ca2+ - dependent modulated positively or negatively by different substances. Once released in the synaptic space, interacts with the serotonin-specific receptors on the postsynaptic cell, capable of spreading the transmission signal and generate the answer phone. The interruption of this signal is due both to the rapid removal of neurotransmitter from synapses that its metabolites, and by specific enzymes in catabolic inactive. The degradation of serotonin is made mainly by monoamine oxidase type A (MAO-A), enzymes located on the mitochondrial membrane and synaptic terminals, which oxidize serotonin 5-HT-indoleacetaldoxime and then converted to acid 5-hydroxy-3-indoleacetic (5-HIAA), whose levels represent a good measure of the turnover of serotonin.
The rapid removal of neurotransmitter from the synaptic space is done by mechanisms re-uptake in the same terminal from which neurotransmitter is released. Many studies of biochemical and pharmacological character focused on mechanisms of re-uptake and the possible significance of these is that pathological physiological situations. The serotonin transporter is the product of a single gene located on human chromosome 17 in region q11.2 near the centromeric. The functional heterogeneity of this protein is provided by the phenomena of splicing at the 5 'and polyadenylation alternative to 5'. Were recently identified several polymorphisms in the promoter of the gene coding for the serotonin transporter, which seem to influence gene expression and protein. In some populations these polymorphisms confer susceptibility to certain illnesses such as depression associated with stress.
The multiplicity of effects mediated by serotonin results from the neurotransmitter with a wide variety of membrane receptors, located both in the nervous system (central and peripheral) both in peripheral organs. They were, in fact, located in organs such as heart and other cardiovascular and intestines.
By convention the serotonin receptors have been divided into seven different subfamilies (5HT1 from a 5-HT7) on the basis of their pharmacological characteristics, the amino acid sequence, gene organization and system of signal transduction coupled to them. Serotonin receptors are almost exclusively type metabotropic, coupled to G proteins, the only ionotropic receptor is the 5-HT3 receptor, ion channel permeable to cations. The structure of the serotonergic receptors coupled to G proteins is very similar to that of any other receptors coupled to protein G. Proteins are closely associated with the double lipid layer, with seven putative transmembrane domains of a hydrophobic segments connected by three intracellular and three other extracellular.
Serotonin effect in various tissues
• Gastrointestinal feature. The 5-HT determines increase of the internal motility, partially for an effect directed on the smooth muscular cells and partially for an indirect effect of excitatory type on the enteric neurons. The 5-HT stimulates also the fluid secretion; moreover it provokes nausea and vomit by means of the stimulation of the smooth muscle and the sensory nerves in the stomach.
• It is gone blood: Usually it has a compulsion action on the large ones is gone, or arteries or veins. Activation of the receivers 5-HT1 gives origin to the vasoconstriction of the large intracranial vessels, whose expansion contributes headache.
• Platelets. 5-HT the cause platelet aggregation through the receivers 5-HT2A, and the platelets that are collected in are gone release other 5-HT. If endothelium is intact, the liberation of 5-HT from the adhesion platelets cause vasodilatation, that it allows the sliding of the blood flow; if it is damaged, 5-HT the cause constriction and hinders the hematic flow ulteriorly.
• Nervous endings and SNC: The 5-HT stimulates the nervous endings sensory nocicettive, mainly through the receivers 5-HT3. If it is inject to cutaneous level it provokes pain. The 5-HT excites some neurons and it inhibits others; moreover it acts to presynaptic level determining inhibition of the release of neurotransmitters from the nervous endings.
In the central nervous system, the serotonin carry out an important role in the regulation humoral, of the sleep, the body temperature, the sexuality and appetite.
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