Top ▲

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).


« Hide More detailed introduction

The 5-HT3 receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-Hydroxytryptamine (serotonin) receptors [18]) 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 [24,35], 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 [15,37,53]. 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 [53]. The co-expression of 5-HT3A and 5-HT3C-E subunits has been demonstrated in human colon [23]. 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 [27,51]. The 5-HT3B subunit imparts distinctive biophysical properties upon hetero-oligomeric 5-HT3AB versus homo-oligomeric 5-HT3A recombinant receptors [9,11,13,21,25,40,44], 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 [27,51]. However, 5-HT3A and 5-HT3AB receptors differ in their allosteric regulation by some general anaesthetic agents, small alcohols and indoles [19,42-43]. The potential diversity of 5-HT3 receptors is increased by alternative splicing of the genes HTR3A and E [7,16,34,36-37]. 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 [21,34,52]. 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


5-HT3AB C Show summary » More detailed page

5-HT3A C Show summary » More detailed page


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


Show »

Further reading

Show »


Show »

NC-IUPHAR subcommittee and family contributors

Show »

How to cite this family page

Database page citation (select format):

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.