5-HT4 receptor

5-Hydroxytryptamine receptor 4 is a protein that in humans is encoded by the HTR4 gene.^[5][6]

HTR4
Identifiers
Aliases	HTR4, 5-HT4, 5-HT4R, 5-HT4 receptor, 5-hydroxytryptamine receptor 4
External IDs	OMIM: 602164; MGI: 109246; HomoloGene: 20243; GeneCards: HTR4; OMA:HTR4 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q32 Start 148,451,032 bp[1] End 148,677,235 bp[1]
Gene location (Mouse) Chr. Chromosome 18 (mouse)[2] Band 18|18 E1 Start 62,457,275 bp[2] End 62,629,648 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in beta cell triceps brachii muscle glutes testicle external globus pallidus vena cava vastus lateralis muscle pars reticulata pars compacta epithelium of nasopharynx Top expressed in lumbar spinal ganglion mucosa of urinary bladder transitional epithelium of urinary bladder olfactory tubercle left colon Paneth cell Region I of hippocampus proper CA3 field perirhinal cortex intestinal villus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity G protein-coupled serotonin receptor activity trace-amine receptor activity identical protein binding neurotransmitter receptor activity protein binding Cellular component cytoplasm integral component of membrane endosome plasma membrane integral component of plasma membrane membrane dendrite Biological process gamma-aminobutyric acid signaling pathway G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger regulation of appetite signal transduction chemical synaptic transmission G protein-coupled serotonin receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3360 15562 Ensembl ENSG00000164270 ENSMUSG00000026322 UniProt Q13639 P97288 RefSeq (mRNA) NM_000870 NM_001040169 NM_001040172 NM_001040173 NM_001040174 NM_001286410 NM_199453 NM_008313 NM_001364956 NM_001364957 NM_001364958 NM_001364959 RefSeq (protein) NP_000861 NP_001035259 NP_001035262 NP_001035263 NP_001273339 NP_955525 NP_032339 NP_001351885 NP_001351886 NP_001351887 NP_001351888 Location (UCSC) Chr 5: 148.45 – 148.68 Mb Chr 18: 62.46 – 62.63 Mb PubMed search [3] [4]
Wikidata
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Function

This gene is a member of the family of human serotonin receptors, which are G protein-coupled receptors that stimulate cAMP production in response to serotonin (5-hydroxytryptamine). The gene product is a glycosylated transmembrane protein that functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. Multiple transcript variants encoding proteins with distinct C-terminal sequences have been described, but the full-length nature of some transcript variants has not been determined.^[7]

Location

The receptor is located in the alimentary tract, urinary bladder, heart and adrenal gland as well as the central nervous system (CNS).^[8] In the CNS the receptor appears in the putamen, caudate nucleus, nucleus accumbens, globus pallidus, and substantia nigra, and to a lesser extent in the neocortex, raphe, pontine nuclei, and some areas of the thalamus. It has not been found in the cerebellum.^[9]

Isoforms

Internalization is isoform-specific.^[10]

Ligands

Several drugs that act as 5-HT₄ selective agonists have recently been introduced into use in both scientific research and clinical medicine. Some drugs that act as 5-HT₄ agonists are also active as 5-HT₃ antagonists, such as mosapride, metoclopramide, renzapride, and zacopride, and so these compounds cannot be considered highly selective. Research in this area is ongoing.^[11] Amongst these agonists prucalopride has >150-fold higher affinity for 5-HT4 receptors than for other receptors.

SB-207,145 radiolabeled with carbon-11 is used as a radioligand for 5-HT₄ in positron emission tomography pig^[12] and human^[13] studies.

Agonists

• Tropisetron^[14] – partial agonist
• BIMU-8
• Cisapride
• CJ-033,466 – partial agonist
• Felcisetrag
• ML-10302^[15]
• Mosapride
• Prucalopride
• Renzapride
• RS-67506
• RS-67333 – partial agonist
• SL65.0155 – partial agonist
• Tegaserod
• Zacopride
• Metoclopramide
• Sulpiride
• Naronapride
• Usmarapride

Antagonists

• L-lysine
• Piboserod
• GR-113,808 (1-methyl-1H-indole-3-carboxylic acid, [1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl ester)^[16]
• GR-125,487
• RS-39604 (1-[4-Amino-5-chloro-2-(3,5-dimethoxyphenyl)methyloxy]-3-[1-[2-methylsulphonylamino]piperidin-4-yl]propan-1-one)
• SB-203,186
• SB-204,070
• ([Methoxy-¹¹C]1-butylpiperidin-4-yl)methyl 4-amino-3-methoxybenzoate^[17]
• Chamomile (ethanol extract)^[18]

See also

• 5-HT receptor
• 5-HT₁ receptor
• 5-HT₂ receptor
• 5-HT₃ receptor
• 5-HT₅ receptor
• 5-HT₆ receptor
• 5-HT₇ receptor