Serotonin neurons (5-HT)
Serotonin is synthesized via two enzymatic steps involving tryptophan hydroxylase and aromatic amino acid decarboxylase. It is then stored in vesicles at the axonal end for release. There have been at least 14 different serotonin receptors subtypes identified. This schematic shows the major postsynaptic and presynaptic receptors. Serotonin is metabolized intra-cellularly by monoamine oxidase (MAO) following reuptake. Much of the research into finding a treatment for various psychiatric diseases (especially depression and anxiety) has focused on controlling serotonin neurotransmission. The physiological function of each receptor subtype has not yet been established, but is currently the subject of intensive
investigation. The following briefly summarizes our understanding of the function of the most widely studied 5-HT receptors: 5-HT1A: Agonists act as anxiolytics and this receptor has also been widely implicated in depression. 5-HT1D: Agonists at this site are effective in treating acute migraine headaches. 5-HT2A: These receptors are associated with neuronal depolarization and blockade is thought to modulate DA release. 5-HT2C: This subtype is thought to be involved in regulating depression, anxiety, satiety and sleep, although no agent solely working on 5HT2C has been marketed. 5-HT3: These receptors appear to be involved in the depolarization of peripheral neurons, pain, and the emesis reflex.
Serotonin, norepinephrine, and dopamine all utilize tyrosine as a substrate for synthesis.
Extra info: Norepinephrine and dopamine use tyrosine, but serotonin uses L-tryptophan as a substrate for synthesis.
Intracellular metabolism of serotonin via monoamine oxidase requires energy from axonal mitochondria.
Extra info: Mitochondria are the principal chemical energy transducers of the cell (except for the 10 reactions of the glycolytic pathway), and thus are responsible for the energy needed for MAO.
The stimulation of 5-HT3 receptors is associated with an increase in nausea.
Extra info: Drugs such as ondansetron which is used for chemotherapy-induced emesis are 5HT3 antagonists.
The 5-HT1D receptor agonists (like sumatriptan) which are used for migraine headaches cause a decrease in serotonin neurotransmission.
Extra info: As can be seen from the graphic, 5HT1D is a presynaptic receptor that inhibits 5HT neurotransmission.