Serotonin

Serotonin is a neurotransmitter in the CNS and a biogenic amine that occurs in large quantities in the intestinal mucosa in stored form.

Serotonin is formed from tryptophan. The enzymes responsible for the synthesis are:

• tryptophan hydrolase.
• the aromatic L-amino acid decarboxylase

Serotonin is broken down via the MAO-A. The resulting main metabolite (5-hydroxyindoleacetic acid) is eliminated renally. In tryptaminergic neurons, the axolemmal serotonin transporter (SERT) is primarily responsible for the removal of synaptic serotonin.

In the CNS, serotonin is involved in many different processes. The importance of serotonin in the development of affective psychoses is undisputed. The large number of symptoms that carcinoids can also cause by the release of serotonin shows the pathogenetic importance of this neurotransmitter in intestinal diseases.

• Currently, 14 different receptors for serotonin are known to be distributed in the cardiovascular system, the central nervous system, the blood vessels and the gastrointestinal tract. The serotonin receptors are also known as 5-HT receptors. They are divided into 4 families:
  • _Gi/o -coupled 5-HT1 and 5-HT5 receptors

  • Gq/11 -coupled 5-HT2 receptors

  • the inotropic 5-HT3 receptor

  • G5 -coupled 5-HT4, 5-HT6 and 5-HT7 receptors
• In the gastrointestinal tract, serotonin stimulates intestinal peristalsis. Elevated serum levels are found in tumours with an affinity for enterochrome, which release more of the hormone. Serotonin has a vasoconstrictive effect in the lungs and kidneys. In the skeletal muscles, on the other hand, it has a vasodilating effect. These vasoactive effects also play a role in the treatment of migraine.
• An intravascular injection of serotonin causes a complex reaction of the cardiovascular system involving several receptors: after an initial drop in blood pressure, there is an increase in blood pressure after a few seconds to finally end in a long-lasting hypotension. In smaller blood vessels it contributes to wound healing by vasoconstricting and promoting blood clotting.
• Central serotonin neurons are believed to help regulate mood, sleep-wake rhythm, pain perception, food intake and body temperature. However, it is controversial whether depression and anxiety disorders are associated with or caused by a real lack of serotonin in the brain.

1. Jimenez-Genchi A (2006) Immediate switching from moclobemide to duloxetine may induce serotonin syndrome. J Clin Psychiatry 67: 1821-1822
2. Ruhe HG et al (2006) Switching antidepressants after a first selective serotonin reuptake inhibitor in major depressive disorder: a systematic review. J Clin Psychiatry 67: 1836-1855
3. Steinberg M et al (2007) Mild serotonin syndrome associated with concurrent linezolid and fluoxetine. At J Health Syst Pharm 64: 59-62