BPS/IUPHAR Guide to Pharmacology | GRAC IC FAMILIES

5-HT₃ receptors

More information on this family may be found on the IUPHAR-DB family and introduction pages.

The 5-HT₃ receptor [nomenclature as agreed by the NC-IUPHAR Subcommittee on 5-hydroxytryptamine (serotonin) receptors [16]] is a ligand-gated ion channel of the Cys-loop family that includes the nicotinic acetylcholine, GABA_Aand strychnine-sensitive glycine receptors. The receptor exists as a pentamer of 4TM subunits that form an intrinsic cation selective channel [2]. 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 (ENSG00000178084), 5-HT3D (ENSG00000186090) and 5-HT3E (ENSG00000186038) subunits [22,32], 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 [13,34,49]. 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 [49]. The co-expression of 5-HT3A and 5-HT3C-E subunits has been demonstrated in human colon [21]. 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 [3], but this is inconsistent with recent reports which show at least one A-A interface [25,47]. The 5-HT3B subunit imparts distinctive biophysical properties upon hetero-oligomeric 5-HT3AB versus homo-oligomeric 5-HT3A recombinant receptors [8,10-11,19,23,37,40], influences the potency of channel blockers, but generally has only a modest effect upon the apparent affinity of agonists, or the affinity of antagonists ([5], but see [7,9-10]) which may be explained by the orthosteric binding site residing at an interface formed between 5-HT3A subunits [25,47]. However, 5-HT₃A and 5-HT₃AB receptors differ in their allosteric regulation by some general anaesthetic agents, small alcohols and indoles [17,38-39]. The potential diversity of 5-HT₃receptors is increased by alternative splicing of the genes HTR3A and E [6,14,31,33-34]. 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 [19,31,48]. To date, inclusion of the 5-HT3A subunit appears imperative for 5-HT₃ receptor function.

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

Channels

5-HT₃AB Show »« Hide

5-HT₃A Show »« Hide

Subunits

5-HT3A Show »« Hide

Nomenclature	5-HT3A
Other names	5-HT_3A , 5-HT₃, HTR3, 5-HT3R, 5-hydroxytryptamine (serotonin) receptor 3A, 5-HT3, 5HT3, 5-HT-3, 5-HT3 receptor, 5-HT3-A, 5-hydroxytryptamine receptor 3, 5-hydroxytryptamine receptor 3A, 5HT3 receptor, serotonin receptor 3A, serotonin-gated ion channel receptor
IUPHAR-DB	5-HT3A
Genes	HTR3A (Hs), Htr3a (Mm), Htr3a (Rn)
Ensembl ID	ENSG00000166736 (Hs), ENSMUSG00000032269 (Mm), ENSRNOG00000006595 (Rn)
Functional characteristics	γ = 0.4-0.8 pS [+ 5-HT3B, γ = 16 pS]; inwardly rectifying current [+ 5-HT3B, rectification reduced]; n_H 2-3 [+ 5-HT3B 1-2]; relative permeability to divalent cations reduced by co-expression of the 5-HT3B subunit

5-HT3B Show »« Hide

Nomenclature	5-HT3B
Other names	5-HT_3B, 5-hydroxytryptamine (serotonin) receptor 3B, 5-HT-3B, 5-HT3-B, 5-hydroxytryptamine receptor 3B, serotonin receptor 3B, 5-HT3 receptor subunit B
IUPHAR-DB	5-HT3B
Genes	HTR3B (Hs), Htr3b (Mm), Htr3b (Rn)
Ensembl ID	ENSG00000149305 (Hs), ENSMUSG00000008590 (Mm), ENSRNOG00000006920 (Rn)
Functional characteristics	γ = 0.4-0.8 pS [+ 5-HT3B, γ = 16 pS]; inwardly rectifying current [+ 5-HT3B, rectification reduced]; n_H 2-3 [+ 5-HT3B 1-2]; relative permeability to divalent cations reduced by co-expression of the 5-HT3B subunit

5-HT3C Show »« Hide

Nomenclature	5-HT3C
Other names	5-HT_3C, HTR3C3, 5-hydroxytryptamine (serotonin) receptor 3, family member C
IUPHAR-DB	5-HT3C
Genes	HTR3C (Hs)
Ensembl ID	ENSG00000178084 (Hs)

5-HT3D Show »« Hide

Nomenclature	5-HT3D
Other names	5-HT_3D, 5-hydroxytryptamine (serotonin) receptor 3 family member D
IUPHAR-DB	5-HT3D
Genes	HTR3D (Hs)
Ensembl ID	ENSG00000186090 (Hs)

5-HT3E Show »« Hide

Nomenclature	5-HT3E
Other names	5-HT_3E, HTR3C1long, 5-hydroxytryptamine (serotonin) receptor 3, family member E
IUPHAR-DB	5-HT3E
Genes	HTR3E (Hs)
Ensembl ID	ENSG00000186038 (Hs)

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