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5-HT3 receptors C

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 [20]) 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 [5]. 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 [26,37], 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 [17,39,55]. 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 [55]. The co-expression of 5-HT3A and 5-HT3C-E subunits has been demonstrated in human colon [25]. 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 [6], but this is inconsistent with recent reports which show at least one A-A interface [29,53]. The 5-HT3B subunit imparts distinctive biophysical properties upon hetero-oligomeric 5-HT3AB versus homo-oligomeric 5-HT3A recombinant receptors [11,13,15,23,27,42,46], influences the potency of channel blockers, but generally has only a modest effect upon the apparent affinity of agonists, or the affinity of antagonists ([8], but see [10,12-13]) which may be explained by the orthosteric binding site residing at an interface formed between 5-HT3A subunits [29,53]. However, 5-HT3A and 5-HT3AB receptors differ in their allosteric regulation by some general anaesthetic agents, small alcohols and indoles [21,44-45]. The potential diversity of 5-HT3 receptors is increased by alternative splicing of the genes HTR3A and E [9,18,36,38-39]. 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 [23,36,54]. To date, inclusion of the 5-HT3A subunit appears imperative for 5-HT3 receptor function.

Channels and Subunits

Targets of relevance to immunopharmacology are highlighted in blue

Complexes

5-HT3AB C Show summary » More detailed page

5-HT3A C Show summary » More detailed page

Subunits

5-HT3A C Show summary » More detailed page

5-HT3B C Show summary » More detailed page

5-HT3C C Show summary » More detailed page

5-HT3D C Show summary » More detailed page

5-HT3E C Show summary » More detailed page

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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

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Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Mathie A, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. Br J Pharmacol. 176 Issue S1: S142-228.