5-HT3

5-HT3


The 5-HT3 receptor is a member of the superfamily of ligand-gated ion channels, a superfamily that also includes the neuronal nicotinic acetylcholine receptors (nAChRs), and the inhibitory neurotransmitter receptors for GABA (both GABAA and GABAA receptors) and glycine.[1][2] The 5-HT3 receptor is most closely related by homology to the nicotinic acetylcholine receptor.

The 5-HT3 receptor consists of 5 subunits arranged around a central ion conducting pore, which is permeable to sodium, potassium, and calcium ions. Binding of the neurotransmitter 5-hydroxytryptamine (serotonin) to the 5-HT3 receptor opens the channel, which, in turn, leads to an excitatory response in neurons. The 5-HT3 receptor differs markedly in structure and mechanism from the other 5-HT receptor subtypes, which are all G-protein-coupled.

Structure

As with other ligand gated ion channels, the 5-HT3 receptor is composed of five subunits pseudo symmetrically arranged about a central ion conducting pore. These subunits are proteins encoded by the HTR3E genes.

A functional channel may be composed of five identical 5-HT3A subunits (homopentameric) or a mixture of 5-HT3A and one of the other four 5-HT3B,[3][4][5][6] 5-HT3C, 5-HT3D, or 5-HT3E subunits (heteropentameric).[7] It appears that only the 5-HT3A subunits form functional homopentameric channels. All other subunit subtypes must heteropentamerize with 5-HT3A subunits to form functional channels.

Tissue distribution

The 5-HT3 receptor is expressed throughout the central and peripheral nervous systems and mediates a variety of physiological functions.[2] On a cellular level, it has been shown that postsynaptic 5-HT3 receptors mediate fast excitatory synaptic transmission in rat neocortical interneurons, amygdala, and hippocampus, and in ferret visual cortex.[8][9][10][11] 5-HT3 receptors are also present on presynaptic nerve terminals, where they are thought to mediate or modulate neurotransmitter release.[12][13][14]

Effects

When the receptor is activated to open the ion channel by agonists, the following effects are observed:

Agonists

Agonists for the receptor include:

Antagonists

Antagonists for the receptor (sorted by their respective therapeutic application) include:

Discovery

Identification of the 5-HT3 receptor did not take place until 1986 because of a lack of selective pharmacological tool.[2] However, with the discovery that the 5-HT3 receptor plays a prominent role in chemotherapy- and radiotherapy-induced vomiting, and the concomitant development of selective 5-HT3 receptor antagonists to suppress these side effects aroused intense interest from the pharmaceutical industry[20][21] and therefore the identification of 5-HT3 receptors in cell lines and native tissues quickly followed.[2]

See also


References

External links

  • Medical Subject Headings (MeSH)