5-HT5A receptor Information & 5-HT5A receptor Links at HealthHaven.com

5-hydroxytryptamine (serotonin) receptor 5A
Identifiers
Symbols	HTR5A; 5-HT5A; MGC138226
External IDs	OMIM: 601305 MGI: 96283 HomoloGene: 22461 IUPHAR: 5-ht5a GeneCards: HTR5A Gene
Gene ontology
Molecular function	• rhodopsin-like receptor activity; • receptor activity; • serotonin receptor activity;
Cellular component	• integral to plasma membrane; • membrane;
Biological process	• signal transduction; • G-protein coupled receptor protein signaling pathway;
RNA expression pattern
	More reference expression data
Orthologs

edit

5-hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein which in humans is encoded by the HTR5A gene.^[1]^[2]

[edit] 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.^[3] This protein has been shown to function in part through the regulation of intracellular Ca²⁺ mobilization.^[1]

Rodents have been shown to possess two functional 5-HT₅ receptor subtypes, 5-HT_5A and 5-HT_5B,^[4] 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.^[5]

[edit] Clinical signficance

The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects.^[1]

[edit] 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.^[6]^[7]

[edit] Agonists

Valerenic acid, a component of valerian, has been shown to act as a 5HT_5A partial agonist.^[8]

Another ligand which has been recently disclosed is shown below, claimed be a selective 5-HT_5A agonist with K_i = 124 nM.^[9]

[edit] Antagonists

Dimebon (non-selective)^[10]
SB-699,551

[edit] See also

5-HT receptor

[edit] References

^ ^a ^b ^c "Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3361.
^ Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (December 1994). "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.
^ Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE (November 1998). "The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells". Eur. J. Pharmacol. 361 (2-3): 299–309. doi:10.1016/S0014-2999(98)00744-4. PMID 9865521.
^ Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, Hen R (March 1993). "Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization". Mol. Pharmacol. 43 (3): 313–9. PMID 8450829. http://molpharm.aspetjournals.org/cgi/reprint/43/3/313.
^ Nelson DL (February 2004). "5-HT5 receptors". Curr Drug Targets CNS Neurol Disord 3 (1): 53–8. doi:10.2174/1568007043482606. PMID 14965244.
^ Wesołowska A (2002). "In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors". Pol J Pharmacol 54 (4): 327–41. PMID 12523486. http://www.if-pan.krakow.pl/pjp/pdf/2002/4_327.pdf.
^ Peters JU, Lübbers T, Alanine A, Kolczewski S, Blasco F, Steward L (January 2008). "Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration". Bioorg. Med. Chem. Lett. 18 (1): 262–6. doi:10.1016/j.bmcl.2007.10.078. PMID 18023344.
^ Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (August 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.
^ Garcia-Ladona, Francisco Javier; Laszlo Szabo & Gerd Steiner et al., "Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances", US 6750221, published 2004-06-15
^ Wu J, Li Q, Bezprozvanny I (2008). "Evaluation of Dimebon in cellular model of Huntington's disease". Mol Neurodegener 3: 15. doi:10.1186/1750-1326-3-15. PMID 18939977.

[edit] 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.

[edit] 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. 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. PMID 12477932.
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. PMID 12690205.
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. PMID 15489334.
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.

This transmembrane receptor-related article is a stub. You can help Wikipedia by expanding it.

[entrez-0] "Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3361.

[pmid7988681-1] Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (December 1994). "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.

[pmid9865521-2] Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE (November 1998). "The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells". Eur. J. Pharmacol. 361 (2-3): 299–309. doi:10.1016/S0014-2999(98)00744-4. PMID 9865521.

[pmid8450829-3] Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, Hen R (March 1993). "Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization". Mol. Pharmacol. 43 (3): 313–9. PMID 8450829. http://molpharm.aspetjournals.org/cgi/reprint/43/3/313.

[pmid14965244-4] Nelson DL (February 2004). "5-HT5 receptors". Curr Drug Targets CNS Neurol Disord 3 (1): 53–8. doi:10.2174/1568007043482606. PMID 14965244.

[pmid12523486-5] Wesołowska A (2002). "In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors". Pol J Pharmacol 54 (4): 327–41. PMID 12523486. http://www.if-pan.krakow.pl/pjp/pdf/2002/4_327.pdf.

[pmid18023344-6] Peters JU, Lübbers T, Alanine A, Kolczewski S, Blasco F, Steward L (January 2008). "Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration". Bioorg. Med. Chem. Lett. 18 (1): 262–6. doi:10.1016/j.bmcl.2007.10.078. PMID 18023344.

[pmid15921820-7] Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (August 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.

[US6750221-8] Garcia-Ladona, Francisco Javier; Laszlo Szabo & Gerd Steiner et al., "Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances", US 6750221, published 2004-06-15

[pmid18939977-9] Wu J, Li Q, Bezprozvanny I (2008). "Evaluation of Dimebon in cellular model of Huntington's disease". Mol Neurodegener 3: 15. doi:10.1186/1750-1326-3-15. PMID 18939977.

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