5-HT3 receptor

Source: Wikipedia, the free encyclopedia.

The 5-HT3 receptor belongs to the

nervous systems.[1]

As with other ligand gated ion channels, the 5-HT3 receptor consists of five subunits arranged around a central ion conducting pore, which is permeable to

anions.[1] They are most closely related by homology to the nicotinic acetylcholine receptor
.

Structure

The 5-HT3 receptor differs markedly in structure and mechanism from the other

transmembrane domain contains the central ion pore, receptor gate, and principle selectivity filter that allows ions to cross the cell membrane.[2]

Human and mouse genes

The genes encoding human 5-HT3 receptors are located on

5-HT efficacies. The pathophysiological role for these additional subunits has yet to be identified.[11]

The human 5-HT3A receptor gene is similar in structure to the mouse gene which has 9 exons and is spread over ~13 kb. Four of its introns are exactly in the same position as the introns in the homologous α7-acetylcholine receptor gene, clearly showing their evolutionary relationship.[12][13]

Figure 2. Structure of the mouse 5HT3 receptor gene, showing its 9 exons (E1-E9), corresponding to the exons shown in the cDNA below. The 5' ends of exons 2, 6, and 9 have alternative splice sites. Figure drawn to scale. Modified after Uetz et al. 1994.[12]

Expression. The 5-HT3C, 5-HT3D and 5-HT3E genes tend to show peripherally restricted pattern of expression, with high levels in the

mRNA
might be greater than for 5-HT3A and 5-HT3B.

Polymorphism. In patients treated with

chemotherapeutic drugs, certain polymorphism of the HTR3B gene could predict successful antiemetic treatment. This could indicate that the 5-HTR3B receptor subunit could be used as biomarker
of antiemetic drug efficacy.

Figure 3. The cDNA sequence of the mouse 5HT3 receptor. The cDNA encodes a 122 nucleotide 5' UTR and a ~510 nucleotide 3' UTR. Boxes indicate exons and the numbers below the exons indicate their length. For instance, the first exon encodes 22 amino acids plus one nucleotide belonging to a split codon with another 2 nucleotides encoded by the next exon. M1-4 indicate the transmembrane helices and C-C indicates the Cysteine loop. Modified after Uetz et al. 1994[12]

Tissue distribution

The 5-HT3 receptor is expressed throughout the central and peripheral nervous systems and mediates a variety of physiological functions.[14] 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.[15][16][17][18] 5-HT3 receptors are also present on presynaptic nerve terminals. There is some evidence for a role in modulation of neurotransmitter release,[19][20] but evidence is inconclusive.[21]

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:

Positive Allosteric Modulators

These agents are not agonists at the receptor, but increase the affinity or efficacy of the receptors for an agonist:

Discovery

Identification of the 5-HT3 receptor did not take place until 1986, lacking selective pharmacological tools.

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[2][33] and therefore the identification of 5-HT3 receptors in cell lines and native tissues quickly followed.[14]

See also

References

External links