5-HT receptors are specialized proteins found on the surface of cells throughout the body, acting as receivers for chemical signals. These receptors are an integral part of the body’s communication network, allowing cells to interact and coordinate various functions. They play a role in processing information and orchestrating responses across numerous biological systems, influencing a wide range of physiological processes.
Understanding Serotonin
Serotonin, also known as 5-hydroxytryptamine (5-HT), is a chemical that functions as both a neurotransmitter and a hormone within the body. It transmits signals between nerve cells in the brain and throughout the peripheral nervous system. Approximately 90% of serotonin is synthesized in the gastrointestinal tract by enterochromaffin cells, and the remaining portion produced in the brain.
The synthesis of serotonin begins with the amino acid L-tryptophan, which is obtained from dietary protein. L-tryptophan is transported into the brain, where the enzyme L-tryptophan hydroxylase (TPH) converts it into 5-hydroxytryptophan (5-HTP). Subsequently, 5-HTP is decarboxylated by L-aromatic amino acid decarboxylase to form serotonin. Once synthesized, serotonin is stored within vesicles in presynaptic neurons and released into the synaptic cleft when stimulated by nerve impulses.
Different Types of 5-HT Receptors
5-HT receptors are categorized into seven main families, labeled 5-HT1 through 5-HT7, with many of these families further divided into multiple subtypes. Most 5-HT receptors are G protein-coupled receptors (GPCRs), meaning they indirectly influence cell activity by initiating a cascade of chemical reactions inside the cell. The exception is the 5-HT3 receptor, which functions as a ligand-gated ion channel, directly opening to allow ions to pass through and change the cell’s electrical potential.
The 5-HT1 receptor family, including subtypes like 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F, are inhibitory and are found in the central nervous system (CNS), particularly in areas like the cerebral cortex, hippocampus, and raphe nuclei. They modulate neurotransmitter release and neuronal activity by inhibiting adenylate cyclase activity. The 5-HT2 family, comprising 5-HT2A, 5-HT2B, and 5-HT2C, are excitatory and are expressed in the cerebral cortex, basal ganglia, and peripheral tissues, where they activate phospholipase C.
The 5-HT3 receptors are excitatory ligand-gated ion channels located in the brain, including the area postrema involved in the vomiting reflex, and also in the gastrointestinal tract. The 5-HT4, 5-HT6, and 5-HT7 receptor families are excitatory, activating adenylate cyclase, and are found in various brain regions such as the hippocampus, as well as in the gut and blood vessels. The 5-HT5 family, consisting of 5-HT5A and 5-HT5B, are inhibitory and located in the brain, influencing processes like sleep and memory.
How 5-HT Receptors Influence the Body and Mind
5-HT receptors exert widespread influence across various physiological and psychological functions. They are involved in regulating mood and play a role in sleep cycles.
Beyond mood and sleep, 5-HT receptors influence appetite and digestion. For instance, serotonin release in the gut can speed up digestion and it also contributes to feelings of fullness during meals. Furthermore, these receptors are involved in pain perception and cognitive functions such as learning and memory.
5-HT Receptors and Medications
Understanding 5-HT receptors has advanced the development of medications designed to modulate their activity. These drugs target specific receptor subtypes to either activate or block their functions, allowing for the treatment of a range of conditions by fine-tuning the serotonergic system.
For example, selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants that block the reuptake of serotonin into presynaptic neurons, increasing its availability in the synapse to improve mood. Triptans, used for migraine relief, act as agonists, meaning they activate certain 5-HT1 receptor subtypes to constrict blood vessels in the brain and inhibit pain signals. Antiemetics, such as ondansetron, are 5-HT3 receptor antagonists that block these receptors, preventing nausea and vomiting. Other medications, including some antipsychotics, target various 5-HT receptors to manage symptoms of conditions like schizophrenia.