5-HT receptor

Synonyms: serotonin receptor, 5-hydroxytryptamine receptor
German: 5-HT-Rezeptor, Serotoninrezeptor, 5-Hydroxytryptamin-Rezeptor

1 Definition
2 Occurrence
3 Classification
4 Effect
- 4.1 G protein–coupled 5-HT receptors
  - 4.1.1 Inhibitory effect
  - 4.1.2 Excitatory effect
- 4.2 Ligand-gated ion channels
5 Clinical significance

1 Definition

5-HT receptors, also known as serotonin receptors are receptors that are activated by serotonin. Almost all serotonin receptors are G protein–coupled receptors, with the exception of the 5-HT3 receptor subfamily which are ligand-gated ion channels.

2 Occurrence

Serotonin receptors are present in the central nervous system, as well as in the peripheral nervous system. They play important roles in various neuronal processes, including memory, mood, thermoregulation, appetite, cognition, and learning.

3 Classification

Serotonin receptors can be grouped into the following families and subfamilies:

Family	G protein	Mechanism of signal transduction	Function	Subtypes
5-HT₁ receptor	G_i/G₀	Decreases intracellular cAMP concentration	Inhibitory	1A, 1B, 1D, 1E, 1F
5-HT₂ receptor	G_q/11	Increases intracellular IP₃ and DAG concentration	Excitatory	2A, 2B, 2C
5-HT₃ receptor	Ligand-gated Na⁺-/K⁺ channel	Depolarizes cell membrane	Excitatory
5-HT₄ receptor	G_s	Increases intracellular cAMP concentration	Excitatory
5-HT₅ receptor	G_i/G₀	Decreases intracellular cAMP concentration	Inhibitory	5A, 5B
5-HT₆ receptor	G_s	Increases intracellular cAMP concentration	Excitatory
5-HT₇ receptor	G_s	Increases intracellular cAMP concentration	Excitatory

4 Effect

4.1 G protein–coupled 5-HT receptors

Except for 5-HT3 receptors, serotonin receptors are G protein-coupled receptors. 5-HT1A, 5-HT1B, 5-HT1D and 5-HT4 receptors inhibit the adenylyl cyclase protein. 5-HT1C and 5-HT2 receptors stimulate the transformation of inositol phosphates.

4.1.1 Inhibitory effect

The activation of, for example, a 5-HT1 receptor in pyramid cells of the hippocampus opens potassium channels via a G protein, which in turn causes the inhibition of neuronal activity due to the resulting hyperpolarization.

4.1.2 Excitatory effect

The activation of a 5-HT2 receptor stimulates phospholipase C which results in the synthesis of the messenger substance IP3 which effects the release of calcium from intracellular reservoirs, triggering the contraction of smooth muscle.

4.2 Ligand-gated ion channels

The 5-HT3 receptor belongs to the group of ligand-gated ion channels and is a non-selective cation channel. The physiologically most relevant ions passing through the channel are sodium and potassium. After the channel opens, Na⁺ flows into the cell and K⁺ leaves the cell, along their respective electrochemical gradients. The result is an ion current that is directed into the cell and results in depolarization. Thus, 5-HT3 receptors are excitatory. So far, they have been found in the autonomic nervous system, sensory pain fibers, and in the brain. The activation of 5-HT3 receptors in the solitary nucleus causes vomiting.