5-HT5A receptor

5-hydroxytryptamine (serotonin) receptor 5A, G protein-coupled
Identifiers
Symbols	HTR5A; 5-HT5A
External IDs	OMIM: 601305 MGI: 96283 HomoloGene: 22461 IUPHAR: 5-ht5a ChEMBL: 3426 GeneCards: HTR5A Gene
Gene Ontology Molecular function • serotonin receptor activity Cellular component • rough endoplasmic reticulum • Golgi apparatus • plasma membrane • integral to plasma membrane • dendrite • perikaryon Biological process • G-protein coupled receptor signaling pathway • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger • serotonin receptor signaling pathway • cAMP-mediated signaling • hippocampus development • response to estradiol stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3361	15563
Ensembl	ENSG00000157219	ENSMUSG00000039106
UniProt	P47898	P30966
RefSeq (mRNA)	NM_024012.3	NM_008314.2
RefSeq (protein)	NP_076917.1	NP_032340.2
Location (UCSC)	Chr 7: 154.86 – 154.88 Mb	Chr 5: 27.84 – 27.86 Mb
PubMed search	[1]	[2]

5-hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein which in humans is encoded by the HTR5A gene.

Function

The gene described in this record is a member of 5-hydroxytryptamine receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G proteins, negatively influencing cAMP levels via G_i and G_o. This protein has been shown to function in part through the regulation of intracellular Ca²⁺ mobilization.

Rodents have been shown to possess two functional 5-HT₅ receptor subtypes, 5-HT_5A and 5-HT_5B, however while humans possess a gene coding for the 5-HT_5B subtype, its coding sequence is interrupted by stop codons making the gene non-functional, and so only the 5-HT_5A subtype is expressed in human brain.

Clinical significance

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects.

Selective Ligands

Few highly selective ligands are commercially available for the 5-HT_5A receptor. When selective activation of this receptor is desired in scientific research, the non-selective serotonin receptor agonist 5-Carboxamidotryptamine can be used in conjunction with selective antagonists for its other targets (principally 5-HT_1A, 5-HT_1B, 5-HT_1D and 5-HT₇). Research in this area is ongoing.

Agonists

• Valerenic acid, a component of valerian, has been shown to act as a 5HT_5A partial agonist.

• Another ligand which has been recently disclosed is shown below, claimed be a selective 5-HT_5A agonist with K_i = 124 nM.

Antagonists

• Latrepirdine (non-selective)
• SB-699,551

See also

• 5-HT receptor

External links

• "5-ht_5a". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2331. 

Further reading

• Raymond JR, Mukhin YV, Gelasco A, et al. (2002). "Multiplicity of mechanisms of serotonin receptor signal transduction.". Pharmacol. Ther. 92 (2-3): 179–212. doi:10.1016/S0163-7258(01)00169-3. PMID 11916537. 
• Thomas DR (2006). "5-ht5A receptors as a therapeutic target.". Pharmacol. Ther. 111 (3): 707–14. doi:10.1016/j.pharmthera.2005.12.006. PMID 16516972. 
• Rees S, den Daas I, Foord S, et al. (1995). "Cloning and characterisation of the human 5-HT5A serotonin receptor.". FEBS Lett. 355 (3): 242–6. doi:10.1016/0014-5793(94)01209-1. PMID 7988681. 
• Schanen NC, Scherer SW, Tsui LC, Francke U (1997). "Assignment of the 5-hydroxytryptamine (serotonin) receptor 5A gene (HTR5A) to human chromosome band 7q36.1.". Cytogenet. Cell Genet. 72 (2-3): 187–8. doi:10.1159/000134184. PMID 8978771. 
• "Toward a complete human genome sequence.". Genome Res. 8 (11): 1097–108. 1999. doi:10.1101/gr.8.11.1097. PMID 9847074. 
• Francken BJ, Josson K, Lijnen P, et al. (2000). "Human 5-hydroxytryptamine(5A) receptors activate coexpressed G(i) and G(o) proteins in Spodoptera frugiperda 9 cells.". Mol. Pharmacol. 57 (5): 1034–44. PMID 10779389. 
• Marazziti D, Ori M, Nardini M, et al. (2001). "mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes.". Neuropsychobiology 43 (3): 123–6. doi:10.1159/000054878. PMID 11287788. 
• Iwata N, Ozaki N, Inada T, Goldman D (2001). "Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia.". Mol. Psychiatry 6 (2): 217–9. doi:10.1038/sj.mp.4000829. PMID 11317225. 
• Grailhe R, Grabtree GW, Hen R (2001). "Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution.". Eur. J. Pharmacol. 418 (3): 157–67. doi:10.1016/S0014-2999(01)00933-5. PMID 11343685. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. //www.ncbi.nlm.nih.gov/pmc/articles/PMC139241/. 
• Noda M, Yasuda S, Okada M, et al. (2003). "Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways.". J. Neurochem. 84 (2): 222–32. doi:10.1046/j.1471-4159.2003.01518.x. PMID 12558985. 
• Scherer SW, Cheung J, MacDonald JR, et al. (2003). "Human chromosome 7: DNA sequence and biology.". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2882961/. 
• Hillier LW, Fulton RS, Fulton LA, et al. (2003). "The DNA sequence of human chromosome 7.". Nature 424 (6945): 157–64. doi:10.1038/nature01782. PMID 12853948. 
• Khorana N, Smith C, Herrick-Davis K, et al. (2003). "Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors.". J. Med. Chem. 46 (18): 3930–7. doi:10.1021/jm030080s. PMID 12930153. 
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. //www.ncbi.nlm.nih.gov/pmc/articles/PMC528928/. 
• Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (2005). "Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro.". Brain Res. Mol. Brain Res. 138 (2): 191–7. doi:10.1016/j.molbrainres.2005.04.009. PMID 15921820. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.