5-HT3 receptors

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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The 5-HT3 receptor [nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-hydroxytryptamine (serotonin) receptors [17]] is a ligand-gated ion channel of the Cys-loop family that includes the zinc-activated channels, nicotinic acetylcholine, GABAA and strychnine-sensitive glycine receptors. The receptor exists as a pentamer of 4TM subunits that form an intrinsic cation selective channel [3]. Five human 5-HT3 receptor subunits have been cloned and homo-oligomeric assemblies of 5-HT3A and hetero-oligomeric assemblies of 5-HT3A and 5-HT3B subunits have been characterised in detail. The 5-HT3C (HTR3C, Q8WXA8), 5-HT3D (HTR3D, Q70Z44) and 5-HT3E (HTR3E, A5X5Y0) subunits [23,34], like the 5-HT3B subunit, do not form functional homomers, but are reported to assemble with the 5-HT3A subunit to influence its functional expression rather than pharmacological profile [14,36,51]. 5-HT3A, -C, -D, and -E subunits also interact with the chaperone RIC-3 which predominantly enhances the surface expression of homomeric 5-HT3A receptor [51]. The co-expression of 5-HT3A and 5-HT3C-E subunits has been demonstrated in human colon [22]. A recombinant hetero-oligomeric 5-HT3AB receptor has been reported to contain two copies of the 5-HT3A subunit and three copies of the 5-HT3B subunit in the order B-B-A-B-A [4], but this is inconsistent with recent reports which show at least one A-A interface [26,49]. The 5-HT3B subunit imparts distinctive biophysical properties upon hetero-oligomeric 5-HT3AB versus homo-oligomeric 5-HT3A recombinant receptors [9,11-12,20,24,39,42], influences the potency of channel blockers, but generally has only a modest effect upon the apparent affinity of agonists, or the affinity of antagonists ([6], but see [8,10-11]) which may be explained by the orthosteric binding site residing at an interface formed between 5-HT3A subunits [26,49]. However, 5-HT3A and 5-HT3AB receptors differ in their allosteric regulation by some general anaesthetic agents, small alcohols and indoles [18,40-41]. The potential diversity of 5-HT3receptors is increased by alternative splicing of the genes HTR3A and E [7,15,33,35-36]. In addition, the use of tissue-specific promoters driving expression from different transcriptional start sites has been reported for the HTR3A, HTR3B, HTR3D and HTR3E genes, which could result in 5-HT3 subunits harbouring different N-termini [20,33,50]. To date, inclusion of the 5-HT3A subunit appears imperative for 5-HT3 receptor function.

Channels

5-HT3AB Show summary » More detailed page

5-HT3A Show summary » More detailed page

Subunits

5-HT3A Show summary » More detailed page

5-HT3B Show summary » More detailed page

5-HT3C Show summary » More detailed page

5-HT3D Show summary » More detailed page

5-HT3E Show summary » More detailed page

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Further reading

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References

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NC-IUPHAR subcommittee and family contributors

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How to cite this family page

Database page citation:

5-HT3 receptors. Accessed on 26/10/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=68.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, Peters JA and Harmar AJ, CGTP Collaborators. (2013) The Concise Guide to PHARMACOLOGY 2013/14: Ligand-Gated Ion Channels. Br J Pharmacol. 170: 1582–1606.