5-HT5A receptor

HTR5A
Identifiers
AliasesHTR5A, 5-HT5A, 5-HT5A receptor, 5-hydroxytryptamine receptor 5A
External IDsMGI: 96283 HomoloGene: 22461 GeneCards: HTR5A
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

3361

15563

Ensembl

ENSG00000157219

ENSMUSG00000039106

UniProt

P47898

P30966

RefSeq (mRNA)

NM_024012

NM_008314

RefSeq (protein)

NP_076917

NP_032340

Location (UCSC)Chr 7: 155.07 – 155.09 MbChr 5: 27.84 – 27.86 Mb
PubMed search[1][2]
Wikidata
View/Edit HumanView/Edit Mouse

5-Hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein that in humans is encoded by the HTR5A gene.[3][4]

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 Gi and Go.[5] This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization.[3] The 5-HT5A receptor has been shown to be functional in a native expression system.[6]

Rodents have been shown to possess two functional 5-HT5 receptor subtypes, 5-HT5A and 5-HT5B,[7] however while humans possess a gene coding for the 5-HT5B subtype, its coding sequence is interrupted by stop codons, making the gene non-functional, and so only the 5-HT5A subtype is expressed in human brain.[8]

It also appears to serve as a presynaptic serotonin autoreceptor.[9]

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.[3]

Selective Ligands

Few highly selective ligands are commercially available for the 5-HT5A 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-HT1A, 5-HT1B, 5-HT1D, and 5-HT7). Research in this area is ongoing.[10][11]

Agonists

Antagonists

See also

References

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. 1 2 3 "Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A".
  4. ↑ Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (Dec 1994). "Cloning and characterisation of the human 5-HT5A serotonin receptor". FEBS Letters. 355 (3): 242–6. PMID 7988681. doi:10.1016/0014-5793(94)01209-1.
  5. ↑ Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE (Nov 1998). "The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells". European Journal of Pharmacology. 361 (2–3): 299–309. PMID 9865521. doi:10.1016/S0014-2999(98)00744-4.
  6. ↑ Goodfellow NM, Bailey CD, Lambe EK (Apr 2012). "The native serotonin 5-HT(5A) receptor: electrophysiological characterization in rodent cortex and 5-HT(1A)-mediated compensatory plasticity in the knock-out mouse". The Journal of Neuroscience. 32 (17): 5804–9. PMC 4644074 Freely accessible. PMID 22539842. doi:10.1523/JNEUROSCI.4849-11.2012.
  7. ↑ Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, Hen R (Mar 1993). "Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization". Molecular Pharmacology. 43 (3): 313–9. PMID 8450829.
  8. ↑ Nelson DL (Feb 2004). "5-HT5 receptors". Current Drug Targets. CNS and Neurological Disorders. 3 (1): 53–8. PMID 14965244. doi:10.2174/1568007043482606.
  9. ↑ {{cite journal | vauthors = Thomas DR, Soffin EM, Roberts C, Kew JN, de la Flor RM, Dawson LA, Fry VA, Coggon SA, Faedo S, Hayes PD, Corbett DF, Davies CH, Hagan JJ | title = SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), a novel 5-ht5A receptor-selective antagonist, enhances 5-HT neuronal function: Evidence for an autoreceptor role for the 5-ht5A receptor in guinea pig brain | journal = Neuropharmacology | volume = 51 | issue = 3 | pages = 566–77 | date = Sep 2006 | pmid = 16846620 | doi = 10.1016/j.neuropharm.2006.04.019 }}
  10. ↑ Wesołowska A (2002). "In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors" (PDF). Polish Journal of Pharmacology. 54 (4): 327–41. PMID 12523486.
  11. ↑ Peters JU, Lübbers T, Alanine A, Kolczewski S, Blasco F, Steward L (Jan 2008). "Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration". Bioorganic & Medicinal Chemistry Letters. 18 (1): 262–6. PMID 18023344. doi:10.1016/j.bmcl.2007.10.078.
  12. ↑ Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (Aug 2005). "Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro". Brain Research. Molecular Brain Research. 138 (2): 191–7. PMID 15921820. doi:10.1016/j.molbrainres.2005.04.009.
  13. ↑ Garcia-Ladona, Francisco Javier; Szabo, Laszlo; Steiner, Gerd; Hofmann, Hans-Peter (2004-06-15). "Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances". Patent US 6750221.
  14. 1 2 3 Yamazaki M, Okabe M, Yamamoto N, Yarimizu J, Harada K (2015). "Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats". J. Pharmacol. Sci. 127 (3): 362–9. PMID 25837935. doi:10.1016/j.jphs.2015.02.006.
  15. ↑ Yamazaki M, Harada K, Yamamoto N, Yarimizu J, Okabe M, Shimada T, Ni K, Matsuoka N (2014). "ASP5736, a novel 5-HT5A receptor antagonist, ameliorates positive symptoms and cognitive impairment in animal models of schizophrenia". Eur Neuropsychopharmacol. 24 (10): 1698–708. PMID 25108314. doi:10.1016/j.euroneuro.2014.07.009.
  16. ↑ Wu J, Li Q, Bezprozvanny I (2008). "Evaluation of Dimebon in cellular model of Huntington's disease". Molecular Neurodegeneration. 3 (1): 15. PMC 2577671 Freely accessible. PMID 18939977. doi:10.1186/1750-1326-3-15.

Further reading

  • Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, Grewal JS, Garnovskaya MN (2002). "Multiplicity of mechanisms of serotonin receptor signal transduction". Pharmacology & Therapeutics. 92 (2–3): 179–212. PMID 11916537. doi:10.1016/S0163-7258(01)00169-3. 
  • Thomas DR (Sep 2006). "5-ht5A receptors as a therapeutic target". Pharmacology & Therapeutics. 111 (3): 707–14. PMID 16516972. doi:10.1016/j.pharmthera.2005.12.006. 
  • Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (Dec 1994). "Cloning and characterisation of the human 5-HT5A serotonin receptor". FEBS Letters. 355 (3): 242–6. PMID 7988681. doi:10.1016/0014-5793(94)01209-1. 
  • 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". Cytogenetics and Cell Genetics. 72 (2–3): 187–8. PMID 8978771. doi:10.1159/000134184. 
  • "Toward a complete human genome sequence". Genome Research. 8 (11): 1097–108. Nov 1998. PMID 9847074. doi:10.1101/gr.8.11.1097. 
  • Francken BJ, Josson K, Lijnen P, Jurzak M, Luyten WH, Leysen JE (May 2000). "Human 5-hydroxytryptamine(5A) receptors activate coexpressed G(i) and G(o) proteins in Spodoptera frugiperda 9 cells". Molecular Pharmacology. 57 (5): 1034–44. PMID 10779389. 
  • Marazziti D, Ori M, Nardini M, Rossi A, Nardi I, Cassano GB (2001). "mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes". Neuropsychobiology. 43 (3): 123–6. PMID 11287788. doi:10.1159/000054878. 
  • Iwata N, Ozaki N, Inada T, Goldman D (Mar 2001). "Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia". Molecular Psychiatry. 6 (2): 217–9. PMID 11317225. doi:10.1038/sj.mp.4000829. 
  • Grailhe R, Grabtree GW, Hen R (Apr 2001). "Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution". European Journal of Pharmacology. 418 (3): 157–67. PMID 11343685. doi:10.1016/S0014-2999(01)00933-5. 
  • Noda M, Yasuda S, Okada M, Higashida H, Shimada A, Iwata N, Ozaki N, Nishikawa K, Shirasawa S, Uchida M, Aoki S, Wada K (Jan 2003). "Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways". Journal of Neurochemistry. 84 (2): 222–32. PMID 12558985. doi:10.1046/j.1471-4159.2003.01518.x. 
  • Khorana N, Smith C, Herrick-Davis K, Purohit A, Teitler M, Grella B, Dukat M, Glennon RA (Aug 2003). "Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors". Journal of Medicinal Chemistry. 46 (18): 3930–7. PMID 12930153. doi:10.1021/jm030080s. 
  • Dietz BM, Mahady GB, Pauli GF, Farnsworth NR (Aug 2005). "Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro". Brain Research. Molecular Brain Research. 138 (2): 191–7. PMID 15921820. doi:10.1016/j.molbrainres.2005.04.009. 

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