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5-HT4 receptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 9

Nomenclature: 5-HT4 receptor

Family: 5-Hydroxytryptamine receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 388 5q32 HTR4 5-hydroxytryptamine receptor 4 7,9,15,21,85,88
Mouse 7 388 18 E1 Htr4 5 hydroxytryptamine (serotonin) receptor 4 22
Rat 7 406 18q12.1 Htr4 5-hydroxytryptamine receptor 4 36,85
Previous and Unofficial Names Click here for help
5-HT4 | serotonin receptor 4 | 5-hydroxytryptamine (serotonin) receptor 4, G protein-coupled
Database Links Click here for help
Specialist databases
GPCRDB 5ht4r_human (Hs), 5ht4r_mouse (Mm), 5ht4r_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
5-hydroxytryptamine

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Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]RS 57639 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Partial agonist 9.3 pKd 14
pKd 9.3 [14]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 8.4 – 8.8 pKd 7
pKd 8.4 – 8.8 [7]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 7.7 pKd 1
pKd 7.7 [1]
PF-04995274 Small molecule or natural product Hs Partial agonist 9.8 pKi 17
pKi 9.8 (Ki 1.5x10-10 M) [17]
Description: Measured at the 5-HT4d receptor.
TD-8954 Small molecule or natural product Primary target of this compound Hs Agonist 9.4 pKi 57
pKi 9.4 [57]
capeserod Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 9.2 pKi 65
pKi 9.2 [65]
RS 57639 Small molecule or natural product Rn Partial agonist 8.6 – 8.9 pKi 14
pKi 8.6 – 8.9 [14]
ML 10302 Small molecule or natural product Hs Partial agonist 7.9 – 9.0 pKi 8-9,61-63
pKi 7.9 – 9.0 (Ki 1.26x10-8 – 1x10-9 M) [8-9,61-63]
RS 67333 Small molecule or natural product Hs Partial agonist 8.2 – 8.7 pKi 61-62
pKi 8.2 – 8.7 [61-62]
relenopride Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Partial agonist 8.3 pKi 37
pKi 8.3 (Ki 4.96x10-9 M) [37]
donecopride Small molecule or natural product Cp Partial agonist 8.2 pKi 49
pKi 8.2 (Ki 6.6x10-9 M) [49]
SC 53116 Small molecule or natural product Mm Full agonist 8.1 pKi 23
pKi 8.1 [23]
tegaserod Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.6 – 8.4 pKi 6-7
pKi 7.6 – 8.4 [6-7]
prucalopride Small molecule or natural product Approved drug Hs Partial agonist 7.0 – 8.6 pKi 7,16
pKi 7.0 – 8.6 [7,16]
velusetrag Small molecule or natural product Primary target of this compound Hs Agonist 7.7 pKi 52,81
pKi 7.7 [52,81]
BIMU 1 Small molecule or natural product Mm Full agonist 7.5 pKi 23
pKi 7.5 [23]
cisapride Small molecule or natural product Approved drug Click here for species-specific activity table Mm Full agonist 7.5 pKi 23
pKi 7.5 [23]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 6.7 – 8.2 pKi 1,14,36
pKi 6.7 – 8.2 [1,14,36]
BIMU 8 Small molecule or natural product Rn Full agonist 7.1 – 7.8 pKi 14
pKi 7.1 – 7.8 [14]
BIMU 8 Small molecule or natural product Mm Full agonist 7.4 pKi 23
pKi 7.4 [23]
cisapride Small molecule or natural product Approved drug Rn Partial agonist 6.8 – 8.0 pKi 1,14
pKi 6.8 – 8.0 [1,14]
BIMU 1 Small molecule or natural product Hs Full agonist 6.4 – 8.4 pKi 9,61-62
pKi 6.4 – 8.4 [9,61-62]
BIMU 8 Small molecule or natural product Hs Full agonist 7.3 pKi 21
pKi 7.3 (Ki 5.01x10-8 M) [21]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Mm Full agonist 7.2 pKi 23
pKi 7.2 [23]
renzapride Small molecule or natural product Rn Full agonist 6.6 – 7.6 pKi 1,14
pKi 6.6 – 7.6 [1,14]
cisapride Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Partial agonist 6.4 – 7.4 pKi 4,7,36,61-62,85
pKi 6.4 – 7.4 [4,7,36,61-62,85]
renzapride Small molecule or natural product Mm Full agonist 6.9 pKi 23
pKi 6.9 [23]
5-MeOT Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 6.3 – 7.4 pKi 1,14,36
pKi 6.3 – 7.4 [1,14,36]
zacopride Small molecule or natural product Mm Full agonist 6.7 pKi 23
pKi 6.7 [23]
5-MeOT Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Mm Full agonist 6.6 pKi 23
pKi 6.6 [23]
mosapride Small molecule or natural product Approved drug Hs Full agonist 6.2 – 6.9 pKi 7
pKi 6.2 – 6.9 [7]
5-hydroxytryptamine Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 5.9 – 7.0 pKi 4,6-7,9,21,61-63,76,85
pKi 5.9 – 7.0 [4,6-7,9,21,61-63,76,85]
zacopride Small molecule or natural product Rn Full agonist 5.9 – 6.9 pKi 1,14
pKi 5.9 – 6.9 [1,14]
renzapride Small molecule or natural product Hs Full agonist 5.9 – 6.8 pKi 4,9,21,36,61-62
pKi 5.9 – 6.8 [4,9,21,36,61-62]
5-MeOT Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.6 – 6.8 pKi 4,7,9,61-62,85
pKi 5.6 – 6.8 [4,7,9,61-62,85]
α-methyl-5-HT Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.6 – 6.6 pKi 1,14
pKi 5.6 – 6.6 [1,14]
metoclopramide Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Mm Full agonist 6.0 pKi 23
pKi 6.0 [23]
α-methyl-5-HT Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.8 pKi 6,36
pKi 5.8 [6,36]
zacopride Small molecule or natural product Hs Full agonist 4.9 – 6.6 pKi 9,21,36
pKi 4.9 – 6.6 [9,21,36]
RS67506 Small molecule or natural product Rn Agonist 8.8 pEC50 39
pEC50 8.8 (EC50 1.58x10-9 M) [39]
vilazodone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.6 pIC50 41
pIC50 6.6 (IC50 2.52x10-7 M) [41]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[123I]SB 207710 Small molecule or natural product Ligand is labelled Ligand is radioactive Pig Antagonist 10.1 pKd 18
pKd 10.1 (Kd 8.6x10-11 M) [18]
[3H]GR 113808 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 9.7 – 10.3 pKd 4,7,63,85
pKd 9.7 – 10.3 (Kd 2x10-10 – 5x10-11 M) [4,7,63,85]
[3H]RS 57639 Small molecule or natural product Ligand is labelled Ligand is radioactive Cp Antagonist 9.7 pKd 14
pKd 9.7 (Kd 2x10-10 M) [14]
[3H]GR 113808 Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Antagonist 9.0 – 9.3 pKd 1,14
pKd 9.0 – 9.3 [1,14]
[11C]SB207145 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.6 pKd 53
pKd 8.6 (Kd 2.8x10-9 M) [53]
GR 125487 Small molecule or natural product Mm Antagonist 10.6 pKi 23
pKi 10.6 [23]
RS 100235 Small molecule or natural product Hs Antagonist 8.7 – 12.2 pKi 21,76
pKi 8.7 – 12.2 (Ki 1.99x10-9 – 6.3x10-13 M) [21,76]
GR 125487 Small molecule or natural product Hs Antagonist 9.8 – 10.7 pKi 21,85
pKi 9.8 – 10.7 [21,85]
SB 207710 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 10.1 – 10.3 pKi 4
pKi 10.1 – 10.3 [4]
SB 204070 Small molecule or natural product Hs Antagonist 9.8 – 10.4 pKi 7,61-62,85
pKi 9.8 – 10.4 (Ki 1.6x10-10 – 3.9x10-11 M) [7,61-62,85]
GR 113808 Small molecule or natural product Hs Antagonist 9.3 – 10.3 pKi 4,7,9,21,62,76,85
pKi 9.3 – 10.3 (Ki 5.1x10-10 – 5x10-11 M) [4,7,9,21,62,76,85]
GR 113808 Small molecule or natural product Mm Antagonist 9.7 pKi 23
pKi 9.7 [23]
piboserod Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.8 – 10.4 pKi 6,21,32
pKi 8.8 – 10.4 [6,21,32]
RS 116 0086 Small molecule or natural product Mm Inverse agonist 9.5 pKi 42
pKi 9.5 [42]
ML 10375 Small molecule or natural product Hs Antagonist 8.8 – 10.0 pKi 6,9,61-63
pKi 8.8 – 10.0 [6,9,61-63]
RO 116 1148 Small molecule or natural product Mm Inverse agonist 9.3 pKi 42
pKi 9.3 [42]
SB 204070 Small molecule or natural product Rn Antagonist 8.9 – 9.5 pKi 14
pKi 8.9 – 9.5 [14]
SB 203186 Small molecule or natural product Hs Antagonist 8.7 – 8.9 pKi 4
pKi 8.7 – 8.9 [4]
GR 113808 Small molecule or natural product Rn Antagonist 8.4 – 8.7 pKi 14
pKi 8.4 – 8.7 [14]
RS 39604 Small molecule or natural product Hs Antagonist 8.2 – 8.7 pKi 61-62,76
pKi 8.2 – 8.7 [61-62,76]
SDZ 205557 Small molecule or natural product Mm Antagonist 8.1 pKi 91
pKi 8.1 [91]
DAU 6285 Small molecule or natural product Hs Antagonist 8.0 pKi 21
pKi 8.0 [21]
SDZ 205557 Small molecule or natural product Rn Antagonist 7.6 – 7.7 pKi 14
pKi 7.6 – 7.7 [14]
DAU 6285 Small molecule or natural product Mm Antagonist 7.3 pKi 23
pKi 7.3 [23]
tropisetron Small molecule or natural product Approved drug Ligand has a PDB structure Mm Antagonist 7.1 pKi 23
pKi 7.1 [23]
tropisetron Small molecule or natural product Approved drug Ligand has a PDB structure Rn Antagonist 6.8 pKi 1
pKi 6.8 [1]
tropisetron Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 6.3 – 7.1 pKi 4,85
pKi 6.3 – 7.1 [4,85]
View species-specific antagonist tables
Antagonist Comments
ML 10375 and SB 207266 have been reported to exert inverse agonist activity on specific 5-HT4 receptor variants but they are very weak inverse agonists when compared to the recently synthesized Roche ligands which exhibit high potent 5-HT4 inverse agonistic activity.
Immunopharmacology Comments
5-HT has been shown to alter cytokine production by dendritic cells via 5-HT4 and 5-HT7 receptors [2].
Cell Type Associations
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
Comment:  Involved in cytokine production/release from DCs.
References:  2,80
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   monocyte (CL:0000576)
macrophage (CL:0000235)
Comment:  Involved in cytokine production/release from DCs.
References:  2,80
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
Calcium channel
Other - See Comments
Comments:  Following cAMP production activation of Ca2+ channels and inhibition of K+ channels have been described in atrial myocytes [71] and neurons [82] respectively. In neurons, 5-HT4 receptors (likely via a cAMP/ Epac pathway) activates the rap1-rac pathway[54].
References:  12,31,33,45,54,71,82
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
G12/G13 family Other - See Comments
Comments:  These transductions have been found in heterologous transfected cells. 5-HT4 receptors activate G13 /Rho-A but not G12 pathway in Insect Sf.9 cells but also in NIH 3T3 and neuroblastoma xglioma cells [73]
References:  73
Tissue Distribution Click here for help
Heart: atria, ventricles.
Species:  Human
Technique:  RT-PCR.
References:  4
Smooth muscle of the rectum.
Species:  Human
Technique:  Radioligand binding.
References:  79
Myenteric plexus and smooth muscle of the colon.
Species:  Human
Technique:  Radioligand binding.
References:  78
Myenteric plexus of the stomach.
Species:  Human
Technique:  Radioligand binding.
References:  77
Esophagus, atrium, sinoatrial node, adrenal gland, frontal cortex.
Species:  Human
Technique:  RT-PCR.
References:  88
Brain: Frontal cortex, hippocampus > caudate, putamen > globus palidus, substantia nigra.
Species:  Human
Technique:  RT-PCR.
References:  88
Brain: striato-nigral system > hippocampus, neocortex and colliculus.
Species:  Human
Technique:  Radioligand binding.
References:  89
Brain: basal ganglia (caudate nucleus, putamen, nucleus accumbens), hippocampal formation (CA1, CA2, CA3 fields, subiculum, dentate gyrus, entorhinal cortex).
Species:  Human
Technique:  in situ hybridisation.
References:  13
Brain: basal ganglia (caudate nucleus, putamen, nucleus accumbens, globus pallidus, substantia nigra) > amygdala, hippocampal formation, cortex.
Species:  Human
Technique:  Radioligand binding.
References:  13
Brain: caudate nucleus > lenticular nucleus, substantia nigra, hippocampus, frontal cortex.
Species:  Human
Technique:  Radioligand binding.
References:  30
Brain: high density in the limbic system (shell nucleus accumbens), hippocampus, in basal ganglia (striatum, globus pallidus) and and substantia nigra (lateral area), in olfactory bulbs and turbercles, and respiratory centers. Moderate in the hypothalamus, amygdala and cerebral cortex. Absent in the raphe nuclei.
Species:  Mouse
Technique:  Radioligand binding.
References:  90
Enteric neurons and smooth muscle of the gut.
Species:  Mouse
Technique:  in situ hybridisation.
References:  51
Small intestine, proximal colon, distal colon.
Species:  Mouse
Technique:  RT-PCR.
References:  51
Respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem.
Species:  Rat
Technique:  Immunohistochemistry.
References:  55
Brain: high density in the limbic system (shell nucleus accumbens), hippocampus, in basal ganglia (striatum, globus pallidus) and and substantia nigra (lateral area), in olfactory bulbs and turbercles, and respiratory centers. Moderate in the hypothalamus, amygdala and cerebral cortex. Absent in the raphe nuclei.
Species:  Rat
Technique:  Radioligand binding.
References:  25,87,90
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of cAMP levels in primary cultures of colliculi neurons which endogenously express 5-HT4 receptors.
Species:  Mouse
Tissue:  Embryo colliculi neurons in primary culture.
Response measured:  Stimulation of cAMP accumulation.
References:  31
Relaxation of the tunica muscularis mucosae of eosophagus.
The muscle is pre-stimulated (contraction) with acetylcholine.
The stimulation of 5-HT4 receptors induces a relaxation.
Species:  Rat
Tissue:  Oesophagus.
Response measured:  Relaxation of pre-contracted oesophagus.
References:  75
Physiological Functions Click here for help
Stimulation of bicarbonate secretion.
Species:  Mouse
Tissue:  Duodenal mucosa and epithelial cells.
References:  84
Reduced respiratory depression induced by opioids.
Species:  Rat
Tissue:  In vivo (respiratory neurons).
References:  55
Potentiation of neurally-mediated contraction of the detrusor muscle.
Species:  Human
Tissue:  Detrusor muscle
References:  28
Stimulation of aldosterone secretion from the adrenal cortex.
Species:  Human
Tissue:  In vivo.
References:  50
Stimulation of gastric emptying.
Species:  Rat
Tissue:  In vivo.
References:  40
Stimulation of gastric emptying.
Species:  Human
Tissue:  In vivo.
References:  29
Stimulation of gastric emptying.
Species:  Mouse
Tissue:  In vivo.
References:  27
Relaxation of ileum.
Species:  Rat
Tissue:  Ileum.
References:  83
Relaxation of oesophagus.
Species:  Rat
Tissue:  Oesophagus tunica muscularis mucosae preparation.
References:  5,66-68,74-75
Relaxation of colon.
Species:  Human
Tissue:  Colonic circular muscle.
References:  58-59
Stimulation of peristaltic reflex (ascending contraction and descending relaxation).
Species:  Human
Tissue:  Jejunum.
References:  34
Stimulation of peristaltic reflex (ascending contraction and descending relaxation).
Species:  Mouse
Tissue:  Colon.
References:  38
Stimulation of lower intestinal propulsion.
Species:  Mouse
Tissue:  In vivo.
References:  67-68
Contraction of colon.
Species:  Rat
Tissue:  Colon.
References:  64,70
Stimulation of peristaltic reflex.
Species:  Rat
Tissue:  Colon.
References:  43
Stimulation of chloride (Cl-) secretion.
Species:  Rat
Tissue:  Colon.
References:  19
Stimulation of Cl- and HCO3- anion secretion and Na+ absorption.
Species:  Rat
Tissue:  Colon.
References:  69
Atrial arrhythmic contractions.
Species:  Human
Tissue:  Atrial tissue.
References:  44
Role in learning and memory.
Species:  Rat
Tissue:  In vivo.
References:  47,56
Role in learning and memory.
Species:  Mouse
Tissue:  In vivo.
References:  35
Role in synaptic plasticity.
Species:  Rat
Tissue:  In vivo.
References:  46-47
Stimulation of food intake.
Species:  Mouse
Tissue:  In vivo.
References:  3
Role in stress-induced anorexia, novelty-induced exploratory activity and seizure susceptibility.
Species:  Mouse
Tissue:  In vivo.
References:  26
Physiological Consequences of Altering Gene Expression Click here for help
5-HT4 receptor knockout mice displayed normal feeding and motor behaviors in baseline conditions but abnormal feeding and locomotor behaviour response to stress and novelty. Specifically, stress-induced hypophagia and novelty-induced exploratory activity are attenuated in the knock-out mice. In addition, mutant mice exhibit hypersensitivity to seizures.This is the first example of a genetic deficit that disrupts the ability of stress to reduce feeding and body weight.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  24,26
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Htr4tm1Comp Htr4tm1Comp/Htr4tm1Comp
involves: 129S1/Sv
MGI:109246  MP:0001259 abnormal body weight PMID: 14724239 
Htr4tm1Comp Htr4tm1Comp/Htr4tm1Comp
involves: 129S1/Sv
MGI:109246  MP:0005449 abnormal food intake PMID: 14724239 
Htr4tm1Comp Htr4tm1Comp/Htr4tm1Comp
involves: 129S1/Sv
MGI:109246  MP:0001417 decreased exploration in new environment PMID: 14724239 
Htr4tm1Comp Htr4tm1Comp/Htr4tm1Comp
involves: 129S1/Sv
MGI:109246  MP:0001783 decreased white adipose tissue amount PMID: 14724239 
Htr4tm1Comp Htr4tm1Comp/Htr4tm1Comp
involves: 129S1/Sv
MGI:109246  MP:0001363 increased anxiety-related response PMID: 14724239 
Htr4tm1Dgen Htr4tm1Dgen/Htr4tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:109246  MP:0005565 increased blood urea nitrogen level
Htr4tm1Comp Htr4tm1Comp/Htr4tm1Comp
involves: 129S1/Sv
MGI:109246  MP:0002906 increased susceptibility to pharmacologically induced seizures PMID: 14724239 
Htr4tm1Comp Htr4tm1Comp/Htr4tm1Comp
involves: 129S1/Sv
MGI:109246  MP:0002080 prenatal lethality PMID: 14724239 
Biologically Significant Variants Click here for help
Type:  Splice variants
Species:  Mouse
Description:  Two splice variants, 5-HT4(a) (previously called 5-HT4S, short form) and 5-HT4(b) (previously called 5-HT4L, long form) have been identified in mice and differ in the length of their carboxy termini.
References:  23
Type:  Splice variant
Species:  Human
Description:  The splice variant 5-HT4(i) has been identified in humans, differing in the length of carboxyl terminal from 5-HT4(g), although sharing the same pharmacological properties. It has been identified by RT-PCR in multiple tissues, such as the brain, heart and colon.
References:  15
Type:  Splice variant
Species:  Human
Description:  The 5-HT4(a) receptor (previously called 5-HT4S, short form) has been identified in the human heart and brain.
References:  10,21,60,72
Type:  Splice variant
Species:  Human
Description:  The 5-HT4(d) receptor splice variant has been identified in humans, differing from the 5-HT4(a) receptor in length of carboxyl terminal.
References:  9,60
Type:  Splice variant
Species:  Human
Description:  The 5-HT4(g) receptor splice variant has been identified in humans, differing from the 5-HT4(a) receptor in length of carboxyl terminal.
References:  60
Type:  Splice variant
Species:  Human
Description:  The 5-HT4(c) receptor splice variant has been identified in humans, differing from the 5-HT4(a) receptor in length of carboxyl terminal.
References:  9,60
Type:  Splice variants
Species:  Human
Description:  The 5-HT4(n) receptor splice variant has been identified in humans, differing from the 5-HT4(a) receptor in length of carboxyl terminal.
References:  88
Type:  Splice variants
Species:  Human
Description:  An internal splice variant of the 5-HT4(b) receptor has been cloned and named 5-HT4(hb). This receptor has a 14 amino acid insertion into the second extracellular loop of the receptor.
References:  7
Type:  Splice variants
Species:  Mouse
Description:  Splice variants 5-HT4(e) and 5-HT4(f) have been cloned from the mouse. They differ in the length and composition of their carboxy termini. They are only expressed in brain tissue and have an increased constitutive activity when compared with the splice variants 5-HT4(a) and 5-HT4(b).
References:  22
Type:  Splice variants
Species:  Rat
Description:  The splice variant 5-HT4(e) has been identified in rats and differs in the length and composition of the its carboxyl terminal.
References:  22
Type:  Splice variants
Species:  Rat
Description:  Two splice variants, 5-HT4(a) (previously called 5-HT4S, short form) and 5-HT4(b) (previously called 5-HT4L, long form) have been identified in rats. They differ in length and sequence of their carboxy termini and have slightly different patterns of expression in the brain and periphery.
References:  36,86
Type:  Splice variants
Species:  Human
Description:  The 5-HT4(b) receptor splice variant has been identified in humans, differing from the 5-HT4(a) receptor in length of carboxyl terminal.
References:  9,20,60,72,85
Biologically Significant Variant Comments
All these splice variants (except 5-HThb) differ at their carboxyl termini after a single position (L358)[11,48].
Please note that the first two 5-HT4 receptor variants to be cloned, 5-HT4S and 5-HT4L, by Gerald et al. 1995 [36], are now called 5-HT4(a) and 5-HT4(b) respectively.

References

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1. Adham N, Gerald C, Schechter L, Vaysse P, Weinshank R, Branchek T. (1996) [3H]5-hydroxytryptamine labels the agonist high affinity state of the cloned rat 5-HT4 receptor. Eur. J. Pharmacol., 304 (1-3): 231-5. [PMID:8813606]

2. Ahern GP. (2011) 5-HT and the immune system. Curr Opin Pharmacol, 11 (1): 29-33. [PMID:21393060]

3. Asakawa A, Ueno N, Katagi M, Ijuin Y, Morita Y, Mizuno S, Inui T, Sakamaki R, Shinfuku N, Uemoto M. (2006) Mosapride improves food intake, while not worsening glycemic control and obesity, in ob/ob obese mice with decreased gastric emptying. J. Diabetes Complicat., 20 (1): 56-8. [PMID:16389169]

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