Serotonin

Serotonin

Chemical Nature/Structure:

Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS) and enterochromaffin cells in the gastrointestinal tract. The neurons in the brain that release serotonin are found in small dense collections of neurons called Raphe Nuclei. The Raphe Nuclei are found in the medulla, pons and midbrain which are all located at the top of the spinal cord. Serotonergic neurons have axons which project to many different parts of the brain, therefore serotonin affects (Rosling, Claire, 2004). In the body, serotonin is synthesized from the amino acid tryptophan by the activity of the enzymes Tryptophan hydroxylase (TPH) and Amino acid decarboxylase (DDC) (Dolnak, Douglas R. DO, 2006). The enzyme tryptophan hydroxylase adds a hydroxyl group to tryptophan's benzene ring at position 5, creating 5-hydroxytryptophan. Another enzyme, amino acid decarboxylase, then removes a carboxyl group from 5-hydroxytryptophan, forming 5-hydroxytryptamine which is more commonly known as serotonin. The average adult human possesses only 5 to 10 mg of serotonin, 90 % of which is in the intestine and the rest in blood platelets and the brain (Rosling, Claire, 2004).

Stimuli necessary for secretion

Serotonin is known to cause vasoconstriction and cellular proliferation in pulmonary arteries. Levels of serotonin are elevated in the plasma of patients with primary pulmonary arterial hypertension (Hippisley-Cox, Julia; Katherine Fielding, and Mike Pringle, 1998). Serotonin is also secreted in excess by carcinoid tumours. Some foods such as bananas, pineapples and walnuts contain serotonin and can increase the excretion of 5-HIAA (Maroteaux, Luc and Canan G. Nebigil, 2003). Studies have shown that serotonin levels are increased with increased exercise and the production of serotonin is increased for some days after the activity (Rosling, Claire, 2004).

Serotonin levels can also be controlled through the diet. A diet deficient in omega-3 fatty acids may lower brain levels of serotonin and cause depression. Complex carbohydrates raise the level of tryptophan in the brain resulting in a calming effect. Vitamin C is also required for the conversion of tryptophan into serotonin (Rosling, Claire, 2004).

Mechanism of Action

Serotonin functions via the MAPK ERK pathway. Binding of 5-HT to the G-coupled, 5-HT receptor activates phospholipase C, which initiates a rapid release of inositol triphosphate and increases intracellular calcium levels. The 5-HT receptor is expressed in the adult cardiovascular system, as well as in the gut and brain (Maroteaux, Luc and Canan G. Nebigil, 2003).

Serotonin is a neurotransmitter involved in the transmission of nerve impulses. Neurotransmitters are chemical messengers within the brain that allow the communication between nerve cells (Rosling, Claire, 2004). Serotonin receptors are divided into seven types, 5-HT1 through 5-HT7, each of which contains several subtypes (Buck, 2006). Packets of serotonin are released from the end of the presynaptic cell into the synaptic cleft. The serotonin molecules can then bind to receptor proteins within the postsynaptic cell, which causes a change in the electrical state of the cell. This change in electrical state can either excite the cell, passing along the chemical message, or inhibit it (Rosling, Claire, 2006). The concentration of serotonin available at postsynaptic receptors is regulated through feedback loops which govern reuptake and metabolism (Buck, 2006). Excess serotonin molecules are taken back up by the presynaptic cell and reprocessed (Rosling, Claire, 2006).

Physiological actions /functions

Serotonin is found in the following 3 main areas of the body: the intestinal wall (where it causes increased gastrointestinal motility), blood vessels (where it causes constriction of large vessels), and the central nervous system. Several lines of evidence suggest that 5-HT regulates cardiovascular function during embryogenesis and adulthood. 5-HT is secreted from enterochromaffin cells into the blood and stored in the platelets. Circulating 5-HT can also be taken up by sympathetic neurons and vascular endothelial cells and can be co-released (Maroteaux, Luc and Canan G. Nebigil, 2003).

Low levels of serotonin are linked to depression, anxiety, and attention deficit disorder. If depression arises as a result of a serotonin deficiency then pharmaceutical agents that increase the amount of serotonin in the brain should be helpful in treating depressed patients. Anti-depressant medications increase