Serotonin: A Multifunctional Neurotransmitter
Serotonin (5-hydroxytryptamine or 5-HT) is a monoamine neurotransmitter that plays crucial roles in numerous physiological functions including mood regulation, sleep, appetite, temperature regulation, learning, memory, and social behavior, with approximately 90% of it produced in the gastrointestinal tract rather than the brain. 1, 2
Biochemistry and Production
- Serotonin is synthesized from the essential amino acid tryptophan 3
- While commonly known as a neurotransmitter in the central nervous system, approximately 90% of serotonin is actually produced in the gastrointestinal tract, particularly in enterochromaffin (EC) cells 4
- The serotonergic system includes a transporter protein in the plasma membrane of neurons that is responsible for serotonin reuptake 1
Receptor System
Serotonin acts through multiple receptor families:
- Seven major receptor families have been identified (5-HT1 through 5-HT7) 1
- Most serotonin receptors are G-protein coupled receptors that activate intracellular second messenger cascades 1
- The 5-HT3 receptor is unique as it functions as a ligand-gated ion channel rather than a G-protein coupled receptor 1, 4
- 5-HT1A receptors function as autoreceptors, inhibiting serotonin release when stimulated 1
- More than 14 different serotonin receptor subtypes exist throughout the body 3
Physiological Functions
Serotonin regulates numerous physiological processes:
Central Nervous System Functions
- Mood regulation and emotional processing
- Sleep-wake cycle regulation
- Appetite control and feeding behavior
- Learning and memory
- Temperature regulation
- Social behavior 1, 5
Peripheral Functions
- Cardiovascular function
- Gastrointestinal motility and secretory reflexes
- Platelet aggregation (through receptor-independent mechanisms)
- Inflammatory and immune responses
- Metabolic regulation in liver and adipose tissues 4, 3, 2
Clinical Significance
- Abnormalities in serotonergic neurotransmission in the brainstem have been implicated in up to 70% of infants who die of Sudden Infant Death Syndrome (SIDS) 6
- Excessive serotonergic activity can lead to serotonin syndrome, a potentially life-threatening condition characterized by mental status changes, autonomic hyperactivity, and neuromuscular abnormalities 7
- Serotonergic medications are used in treating various conditions including depression, anxiety, and obesity 6, 3
- Liraglutide, a glucagon-like peptide 1 receptor agonist, has been approved for obesity treatment and works through pathways that interact with serotonergic systems 6
Pathophysiological Implications
- Dysregulation of serotonin has been linked to various pathological conditions:
- Brainstem abnormalities involving the serotonin (5-HT) system have been confirmed in several independent studies of SIDS cases 6
Pharmacological Targeting
- Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine act primarily at the serotonin transporter protein to increase serotonin availability 1
- Multiple drugs target various serotonin receptors for treating conditions ranging from psychiatric disorders to gastrointestinal diseases 4, 2
- Caution must be exercised when combining serotonergic medications due to the risk of serotonin syndrome 7
Serotonin's widespread distribution and diverse functions throughout the body make it a critical neurotransmitter with implications for numerous physiological processes and disease states, extending far beyond its commonly recognized role in mood regulation.