At the same time from a very early stage of gestation, fetus also starts synthesizing its own serotonin in a special group of nuclei of the midbrain. Soon after serotonergic neurons distribute it throughout the brain and body of the fetus in turn increases division, migration and maturation of both central and peripheral tissues.
Serotonin, which is also known as 5-hydroxytryptamine 5-HT , acts both as neurotransmitter and hormone and is mainly found in the brain, bowels and blood platelets. In , Rapport identified a serum agent that affected vascular tone and called it serotonin. Later, in , he identified chemical composition of serotonin and named it 5-hydroxytryptamine.
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Serotonin, a biogenic amine is produced by the conversion of amino acid tryptophan in the presence of an enzyme tryptophan hydroxylase TPH that exists both in brain and bowel. Enteroendocrine cells derived 5-HT acts also as a hormone, which perform multiple functions including inhibition of osteoblast proliferation and promotion of hepatic regeneration. In the central nervous system, serotonin is synthesized by the neurons of the Raphe nuclei from the amino acid tryptophan through a short metabolic pathway that contains two enzymes: tryptophan hydroxylase and amino acid decarboxylase, and is distributed along the length of the brainstem.
Serotonin is released from the varicosities along the axon into the extra-neuronal space this provides a larger area for serotonin to activate its receptors that exist on the dendrites, the cell bodies and the presynaptic terminals of the adjacent neurons. Thus serotonin not only stimulates postsynaptic serotonin receptors but also present on the extrasynaptic neurons. Thus, it is not a surprise to find significant role of serotonin in the modulation of many behavioral and psychotic disorders such as mood, sleep, appetite, vomiting, sexuality, memory, learning, temperature, cardiovascular and endocrine regulation.
Both high and low levels of serotonin have harmful effect. It is important to mention here that serotonin is required for the metabolism of stress hormone. Scientific evidence confirms that genetic polymorphisms in the enzyme tryptophan hydroxylase in both TPH1 and TPH2 forms can affect the susceptibility to depression and anxiety.
Furthermore, ovarian hormones can affect the expression of tryptophan hydroxylase, triggering postnatal depression and premenstrual stress syndrome, and expression of abnormal serotonergic neurons in infants may lead to high possibility of having sudden infant death syndrome SIDS.
Microscopy Reveals Serotonin Receptor in Action | Technology Networks
Serotonin is also involved in the regeneration of organs such as liver and bone and induces cell division throughout the body. Large diversity of serotonin receptors creates its pharmacological complexity. There are at least seven types and eight subtypes of serotonin receptors that have been identified in different areas of the body, and they all have diverse effects.
A small dose of ecstasy, for example, stimulates a big release of serotonin in the body causing feelings of well-being and comfort but with many side effects. Activation of 5-HT1B and 1D receptors cause vasoconstriction and their antagonists are used for the treatment of schizophrenia and migraines and their partial agonist acts as therapeutic targets for anxiety and depression. Similarly, 5-HT2 receptor has three subtypes 5-HT2A—2C and responsible for sleep, pain and motor regulation and are targeted for conditions such as anxiety, migraine and eating disorders.
There are certain psychiatric medications that modulate the levels of serotonin in the human body. These drugs are classified into four general categories: 1 monoamine oxidase inhibitors MAO , 2 tricyclic TCA antidepressants, 3 atypical antipsychotics and 4 selective serotonin reuptake inhibitors SSRIs.
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SSRIs are prescribed for the treatment of social phobia, anxiety disorders, panic disorders, obsessive-compulsive disorders OCD , major depression, irritable bowel syndrome IBS and eating disorders. It is vital to know the mechanism of neuronal communication to understand the mode of action of SSRIs.
New images show serotonin activating its receptor for first time
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MOLECULAR IMAGING WITH PET
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PET imaging of serotonin system
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