5-HT5A receptor: Difference between revisions

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{{Wrongtitle|title=5-HT<sub>5A</sub> receptor}}
{{DISPLAYTITLE:5-HT<sub>5A</sub> receptor}}
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{{Infobox_gene}}
{{PBB_Controls
'''5-Hydroxytryptamine (serotonin) receptor 5A''', also known as '''HTR5A''', is a [[protein]] that in humans is encoded by the ''HTR5A'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3361| accessdate = }}</ref><ref name="pmid7988681">{{cite journal | vauthors = Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M | title = Cloning and characterisation of the human 5-HT5A serotonin receptor | journal = FEBS Letters | volume = 355 | issue = 3 | pages = 242–6 | date = Dec 1994 | pmid = 7988681 | doi = 10.1016/0014-5793(94)01209-1 }}</ref>
| update_page = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = 5-hydroxytryptamine (serotonin) receptor 5A
| HGNCid = 5300
| Symbol = HTR5A
| AltSymbols =; 5-HT5A; MGC138226
| OMIM = 601305
| ECnumber = 
| Homologene = 22461
| MGIid = 96283
| GeneAtlas_image1 = PBB_GE_HTR5A_221362_at_tn.png
| Function = {{GNF_GO|id=GO:0001584 |text = rhodopsin-like receptor activity}} {{GNF_GO|id=GO:0004872 |text = receptor activity}} {{GNF_GO|id=GO:0004993 |text = serotonin receptor activity}}
| Component = {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007186 |text = G-protein coupled receptor protein signaling pathway}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3361
    | Hs_Ensembl = ENSG00000157219
    | Hs_RefseqProtein = NP_076917
    | Hs_RefseqmRNA = NM_024012
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 7
    | Hs_GenLoc_start = 154492967
    | Hs_GenLoc_end = 154508392
    | Hs_Uniprot = P47898
    | Mm_EntrezGene = 15563
    | Mm_Ensembl = ENSMUSG00000039106
    | Mm_RefseqmRNA = NM_008314
    | Mm_RefseqProtein = NP_032340
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 28172734
    | Mm_GenLoc_end = 28185873
    | Mm_Uniprot = Q3URB0
  }}
}}
'''5-hydroxytryptamine (serotonin) receptor 5A''', also known as '''HTR5A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3361| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The gene described in this record is a member of [[5-HT receptor|5-hydroxytryptamine receptor]] family and encodes a multi-pass membrane protein that functions as a receptor for [[5-hydroxytryptamine]] and couples to [[G protein]]s, negatively influencing cAMP levels via G<sub>i</sub> and G<sub>o</sub>.<ref name="pmid9865521">{{cite journal | vauthors = Francken BJ, Jurzak M, Vanhauwe JF, Luyten WH, Leysen JE | title = The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells | journal = European Journal of Pharmacology | volume = 361 | issue = 2–3 | pages = 299–309 | date = Nov 1998 | pmid = 9865521 | doi = 10.1016/S0014-2999(98)00744-4 }}</ref> This protein has been shown to function in part through the regulation of intracellular Ca<sup>2+</sup> mobilization.<ref name="entrez"/> The 5-HT<sub>5A</sub> receptor has been shown to be functional in a native expression system.<ref>{{cite journal | vauthors = Goodfellow NM, Bailey CD, Lambe EK | title = The native serotonin 5-HT(5A) receptor: electrophysiological characterization in rodent cortex and 5-HT(1A)-mediated compensatory plasticity in the knock-out mouse | journal = The Journal of Neuroscience | volume = 32 | issue = 17 | pages = 5804–9 | date = Apr 2012 | pmid = 22539842 | doi = 10.1523/JNEUROSCI.4849-11.2012 | pmc=4644074}}</ref>
{{PBB_Summary
| section_title =
| summary_text = The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has been implicated in a wide range of psychiatric conditions and also has vasoconstrictive and vasodilatory effects. The gene described in this record is a member of 5-hydroxytryptamine (serotonin) receptor family and encodes a multi-pass membrane protein that functions as a receptor for 5-hydroxytryptamine and couples to G-proteins. This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization.<ref name="entrez">{{cite web | title = Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3361| accessdate = }}</ref>
}}


==See also==
Rodents have been shown to possess two functional 5-HT<sub>5</sub> receptor subtypes, 5-HT<sub>5A</sub> and 5-HT<sub>5B</sub>,<ref name="pmid8450829">{{cite journal | vauthors = Matthes H, Boschert U, Amlaiky N, Grailhe R, Plassat JL, Muscatelli F, Mattei MG, Hen R | title = Mouse 5-hydroxytryptamine5A and 5-hydroxytryptamine5B receptors define a new family of serotonin receptors: cloning, functional expression, and chromosomal localization | journal = Molecular Pharmacology | volume = 43 | issue = 3 | pages = 313–9 | date = Mar 1993 | pmid = 8450829 | doi =  | url = http://molpharm.aspetjournals.org/cgi/reprint/43/3/313 }}</ref> however while humans possess a gene coding for the 5-HT<sub>5B</sub> subtype, its coding sequence is interrupted by stop codons, making the gene non-functional, and so only the 5-HT<sub>5A</sub> subtype is expressed in human brain.<ref name="pmid14965244">{{cite journal | vauthors = Nelson DL | title = 5-HT5 receptors | journal = Current Drug Targets. CNS and Neurological Disorders | volume = 3 | issue = 1 | pages = 53–8 | date = Feb 2004 | pmid = 14965244 | doi = 10.2174/1568007043482606 }}</ref>
 
It also appears to serve as a presynaptic serotonin autoreceptor.<ref name="pmid16846620">{{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 }}</ref>
 
== 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.<ref name="entrez"/>
 
== Selective Ligands ==
 
Few highly selective ligands are commercially available for the 5-HT<sub>5A</sub> 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<sub>1A</sub>, 5-HT<sub>1B</sub>, 5-HT<sub>1D</sub>, and 5-HT<sub>7</sub>). Research in this area is ongoing.<ref name="pmid12523486">{{cite journal | vauthors = Wesołowska A | title = In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors | journal = Polish Journal of Pharmacology | volume = 54 | issue = 4 | pages = 327–41 | year = 2002 | pmid = 12523486 | doi =  | url = http://www.if-pan.krakow.pl/pjp/pdf/2002/4_327.pdf }}</ref><ref name="pmid18023344">{{cite journal | vauthors = Peters JU, Lübbers T, Alanine A, Kolczewski S, Blasco F, Steward L | title = Cyclic guanidines as dual 5-HT5A/5-HT7 receptor ligands: optimising brain penetration | journal = Bioorganic & Medicinal Chemistry Letters | volume = 18 | issue = 1 | pages = 262–6 | date = Jan 2008 | pmid = 18023344 | doi = 10.1016/j.bmcl.2007.10.078 }}</ref>
 
=== Agonists ===
 
* [[Valerenic acid]], a component of [[Valerian (herb)|valerian]], has been shown to act as a 5HT<sub>5A</sub> partial agonist.<ref name="pmid15921820">{{cite journal | vauthors = Dietz BM, Mahady GB, Pauli GF, Farnsworth NR | title = Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro | journal = Brain Research. Molecular Brain Research | volume = 138 | issue = 2 | pages = 191–7 | date = Aug 2005 | pmid = 15921820 | doi = 10.1016/j.molbrainres.2005.04.009 }}</ref>
*[[Olanzapine]], an [[atypical antipsychotic]].<ref>Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.</ref>
* Another ligand that has been recently disclosed is shown below, claimed be a selective 5-HT<sub>5A</sub> agonist with K<sub>i</sub> = 124 nM.<ref name = "US6750221" >{{Cite journal | author-last = Garcia-Ladona | author-first = Francisco Javier | author2-last = Szabo | author2-first = Laszlo | author3-last = Steiner | author3-first = Gerd | author4-last = Hofmann | author4-first = Hans-Peter | publication-date = 2004-06-15 | title = Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances | location= Patent US 6750221}}</ref>
 
[[Image:DE19900637A1 5HT5A ligand.png|200px]]
 
=== Antagonists ===
 
* [[Astellas Pharma|ASP]]-5736<ref name="pmid25837935">{{cite journal |vauthors=Yamazaki M, Okabe M, Yamamoto N, Yarimizu J, Harada K |title=Novel 5-HT5A receptor antagonists ameliorate scopolamine-induced working memory deficit in mice and reference memory impairment in aged rats |journal=J. Pharmacol. Sci. |volume=127 |issue=3 |pages=362–9 |year=2015 |pmid=25837935 |doi=10.1016/j.jphs.2015.02.006 |url=}}</ref><ref name="pmid25108314">{{cite journal |vauthors=Yamazaki M, Harada K, Yamamoto N, Yarimizu J, Okabe M, Shimada T, Ni K, Matsuoka N |title=ASP5736, a novel 5-HT5A receptor antagonist, ameliorates positive symptoms and cognitive impairment in animal models of schizophrenia |journal=Eur Neuropsychopharmacol |volume=24 |issue=10 |pages=1698–708 |year=2014 |pmid=25108314 |doi=10.1016/j.euroneuro.2014.07.009 |url=}}</ref>
* AS-2030680<ref name="pmid25837935"/>
* AS-2674723<ref name="pmid25837935"/>
* [[Latrepirdine]] (non-selective)<ref name="pmid18939977">{{cite journal | vauthors = Wu J, Li Q, Bezprozvanny I | title = Evaluation of Dimebon in cellular model of Huntington's disease | journal = Molecular Neurodegeneration | volume = 3 | issue = 1 | pages = 15 | year = 2008 | pmid = 18939977 | pmc = 2577671 | doi = 10.1186/1750-1326-3-15 }}</ref>
* [[Risperidone]] (non-selective), moderate 206nM affinity.
* [[SB-699,551]]
 
== See also ==
* [[5-HT receptor]]
* [[5-HT receptor]]
* [[5-HT1 receptor|5-HT<sub>1</sub> receptor]]
* [[5-HT2 receptor|5-HT<sub>2</sub> receptor]]
* [[5-HT3 receptor|5-HT<sub>3</sub> receptor]]
* [[5-HT4 receptor|5-HT<sub>4</sub> receptor]]
* [[5-HT6 receptor|5-HT<sub>6</sub> receptor]]
* [[5-HT7 receptor|5-HT<sub>7</sub> receptor]]


==References==
== References ==
{{reflist|2}}
{{reflist|33em}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin|33em}}
{{PBB_Further_reading
* {{cite journal | vauthors = Raymond JR, Mukhin YV, Gelasco A, Turner J, Collinsworth G, Gettys TW, Grewal JS, Garnovskaya MN | title = Multiplicity of mechanisms of serotonin receptor signal transduction | journal = Pharmacology & Therapeutics | volume = 92 | issue = 2–3 | pages = 179–212 | year = 2002 | pmid = 11916537 | doi = 10.1016/S0163-7258(01)00169-3 }}
| citations =
* {{cite journal | vauthors = Thomas DR | title = 5-ht5A receptors as a therapeutic target | journal = Pharmacology & Therapeutics | volume = 111 | issue = 3 | pages = 707–14 | date = Sep 2006 | pmid = 16516972 | doi = 10.1016/j.pharmthera.2005.12.006 }}
*{{cite journal | author=Raymond JR, Mukhin YV, Gelasco A, ''et al.'' |title=Multiplicity of mechanisms of serotonin receptor signal transduction. |journal=Pharmacol. Ther. |volume=92 |issue= 2-3 |pages= 179-212 |year= 2002 |pmid= 11916537 |doi= }}
* {{cite journal | vauthors = Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M | title = Cloning and characterisation of the human 5-HT5A serotonin receptor | journal = FEBS Letters | volume = 355 | issue = 3 | pages = 242–6 | date = Dec 1994 | pmid = 7988681 | doi = 10.1016/0014-5793(94)01209-1 }}
*{{cite journal | author=Thomas DR |title=5-ht5A receptors as a therapeutic target. |journal=Pharmacol. Ther. |volume=111 |issue= 3 |pages= 707-14 |year= 2006 |pmid= 16516972 |doi= 10.1016/j.pharmthera.2005.12.006 }}
* {{cite journal | vauthors = Schanen NC, Scherer SW, Tsui LC, Francke U | title = Assignment of the 5-hydroxytryptamine (serotonin) receptor 5A gene (HTR5A) to human chromosome band 7q36.1 | journal = Cytogenetics and Cell Genetics | volume = 72 | issue = 2–3 | pages = 187–8 | year = 1997 | pmid = 8978771 | doi = 10.1159/000134184 }}
*{{cite journal | author=Rees S, den Daas I, Foord S, ''et al.'' |title=Cloning and characterisation of the human 5-HT5A serotonin receptor. |journal=FEBS Lett. |volume=355 |issue= 3 |pages= 242-6 |year= 1995 |pmid= 7988681 |doi= }}
* {{cite journal | vauthors = | title = Toward a complete human genome sequence | journal = Genome Research | volume = 8 | issue = 11 | pages = 1097–108 | date = Nov 1998 | pmid = 9847074 | doi = 10.1101/gr.8.11.1097 }}
*{{cite journal | author=Schanen NC, Scherer SW, Tsui LC, Francke U |title=Assignment of the 5-hydroxytryptamine (serotonin) receptor 5A gene (HTR5A) to human chromosome band 7q36.1. |journal=Cytogenet. Cell Genet. |volume=72 |issue= 2-3 |pages= 187-8 |year= 1997 |pmid= 8978771 |doi= }}
* {{cite journal | vauthors = Francken BJ, Josson K, Lijnen P, Jurzak M, Luyten WH, Leysen JE | title = Human 5-hydroxytryptamine(5A) receptors activate coexpressed G(i) and G(o) proteins in Spodoptera frugiperda 9 cells | journal = Molecular Pharmacology | volume = 57 | issue = 5 | pages = 1034–44 | date = May 2000 | pmid = 10779389 | doi =  }}
*{{cite journal | author= |title=Toward a complete human genome sequence. |journal=Genome Res. |volume=8 |issue= 11 |pages= 1097-108 |year= 1999 |pmid= 9847074 |doi= }}
* {{cite journal | vauthors = Marazziti D, Ori M, Nardini M, Rossi A, Nardi I, Cassano GB | title = mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes | journal = Neuropsychobiology | volume = 43 | issue = 3 | pages = 123–6 | year = 2001 | pmid = 11287788 | doi = 10.1159/000054878 }}
*{{cite journal | author=Francken BJ, Josson K, Lijnen P, ''et al.'' |title=Human 5-hydroxytryptamine(5A) receptors activate coexpressed G(i) and G(o) proteins in Spodoptera frugiperda 9 cells. |journal=Mol. Pharmacol. |volume=57 |issue= 5 |pages= 1034-44 |year= 2000 |pmid= 10779389 |doi=  }}
* {{cite journal | vauthors = Iwata N, Ozaki N, Inada T, Goldman D | title = Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia | journal = Molecular Psychiatry | volume = 6 | issue = 2 | pages = 217–9 | date = Mar 2001 | pmid = 11317225 | doi = 10.1038/sj.mp.4000829 }}
*{{cite journal | author=Marazziti D, Ori M, Nardini M, ''et al.'' |title=mRNA expression of serotonin receptors of type 2C and 5A in human resting lymphocytes. |journal=Neuropsychobiology |volume=43 |issue= 3 |pages= 123-6 |year= 2001 |pmid= 11287788 |doi= }}
* {{cite journal | vauthors = Grailhe R, Grabtree GW, Hen R | title = Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution | journal = European Journal of Pharmacology | volume = 418 | issue = 3 | pages = 157–67 | date = Apr 2001 | pmid = 11343685 | doi = 10.1016/S0014-2999(01)00933-5 }}
*{{cite journal | author=Iwata N, Ozaki N, Inada T, Goldman D |title=Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia. |journal=Mol. Psychiatry |volume=6 |issue= 2 |pages= 217-9 |year= 2001 |pmid= 11317225 |doi= 10.1038/sj.mp.4000829 }}
* {{cite journal | vauthors = Noda M, Yasuda S, Okada M, Higashida H, Shimada A, Iwata N, Ozaki N, Nishikawa K, Shirasawa S, Uchida M, Aoki S, Wada K | title = Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways | journal = Journal of Neurochemistry | volume = 84 | issue = 2 | pages = 222–32 | date = Jan 2003 | pmid = 12558985 | doi = 10.1046/j.1471-4159.2003.01518.x }}
*{{cite journal | author=Grailhe R, Grabtree GW, Hen R |title=Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution. |journal=Eur. J. Pharmacol. |volume=418 |issue= 3 |pages= 157-67 |year= 2001 |pmid= 11343685 |doi= }}
* {{cite journal | vauthors = Khorana N, Smith C, Herrick-Davis K, Purohit A, Teitler M, Grella B, Dukat M, Glennon RA | title = Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors | journal = Journal of Medicinal Chemistry | volume = 46 | issue = 18 | pages = 3930–7 | date = Aug 2003 | pmid = 12930153 | doi = 10.1021/jm030080s }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Dietz BM, Mahady GB, Pauli GF, Farnsworth NR | title = Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro | journal = Brain Research. Molecular Brain Research | volume = 138 | issue = 2 | pages = 191–7 | date = Aug 2005 | pmid = 15921820 | doi = 10.1016/j.molbrainres.2005.04.009 }}
*{{cite journal | author=Noda M, Yasuda S, Okada M, ''et al.'' |title=Recombinant human serotonin 5A receptors stably expressed in C6 glioma cells couple to multiple signal transduction pathways. |journal=J. Neurochem. |volume=84 |issue= 2 |pages= 222-32 |year= 2003 |pmid= 12558985 |doi=  }}
*{{cite journal  | author=Scherer SW, Cheung J, MacDonald JR, ''et al.'' |title=Human chromosome 7: DNA sequence and biology. |journal=Science |volume=300 |issue= 5620 |pages= 767-72 |year= 2003 |pmid= 12690205 |doi= 10.1126/science.1083423 }}
*{{cite journal  | author=Hillier LW, Fulton RS, Fulton LA, ''et al.'' |title=The DNA sequence of human chromosome 7. |journal=Nature |volume=424 |issue= 6945 |pages= 157-64 |year= 2003 |pmid= 12853948 |doi= 10.1038/nature01782 }}
*{{cite journal | author=Khorana N, Smith C, Herrick-Davis K, ''et al.'' |title=Binding of tetrahydrocarboline derivatives at human 5-HT5A receptors. |journal=J. Med. Chem. |volume=46 |issue= 18 |pages= 3930-7 |year= 2003 |pmid= 12930153 |doi= 10.1021/jm030080s }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Dietz BM, Mahady GB, Pauli GF, Farnsworth NR |title=Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro. |journal=Brain Res. Mol. Brain Res. |volume=138 |issue= 2 |pages= 191-7 |year= 2005 |pmid= 15921820 |doi= 10.1016/j.molbrainres.2005.04.009 }}
}}
{{refend}}
{{refend}}
== External links ==
* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2331 | title = 5-ht<sub>5a</sub>  | accessdate = | authorlink = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | archiveurl = | archivedate = | quote = }}
* {{UCSC gene info|HTR5A}}


{{NLM content}}
{{NLM content}}
{{membrane-protein-stub}}
 
{{G protein-coupled receptors}}
{{G protein-coupled receptors|g1}}
[[Category:G protein coupled receptors]]
{{Serotonergics}}
 
{{DEFAULTSORT:5-Ht5a Receptor}}
[[Category:Serotonin receptors]]

Latest revision as of 01:51, 4 January 2019

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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

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.[3] This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization.[1] The 5-HT5A receptor has been shown to be functional in a native expression system.[4]

Rodents have been shown to possess two functional 5-HT5 receptor subtypes, 5-HT5A and 5-HT5B,[5] 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.[6]

It also appears to serve as a presynaptic serotonin autoreceptor.[7]

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.[1]

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.[8][9]

Agonists

Antagonists

See also

References

  1. ↑ 1.0 1.1 1.2 "Entrez Gene: HTR5A 5-hydroxytryptamine (serotonin) receptor 5A".
  2. ↑ 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. doi:10.1016/0014-5793(94)01209-1. PMID 7988681.
  3. ↑ 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. doi:10.1016/S0014-2999(98)00744-4. PMID 9865521.
  4. ↑ 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. doi:10.1523/JNEUROSCI.4849-11.2012. PMC 4644074. PMID 22539842.
  5. ↑ 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.
  6. ↑ Nelson DL (Feb 2004). "5-HT5 receptors". Current Drug Targets. CNS and Neurological Disorders. 3 (1): 53–8. doi:10.2174/1568007043482606. PMID 14965244.
  7. ↑ 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 (Sep 2006). "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". Neuropharmacology. 51 (3): 566–77. doi:10.1016/j.neuropharm.2006.04.019. PMID 16846620.
  8. ↑ 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.
  9. ↑ 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. doi:10.1016/j.bmcl.2007.10.078. PMID 18023344.
  10. ↑ 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. doi:10.1016/j.molbrainres.2005.04.009. PMID 15921820.
  11. ↑ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  12. ↑ 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.
  13. ↑ 13.0 13.1 13.2 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. doi:10.1016/j.jphs.2015.02.006. PMID 25837935.
  14. ↑ 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. doi:10.1016/j.euroneuro.2014.07.009. PMID 25108314.
  15. ↑ Wu J, Li Q, Bezprozvanny I (2008). "Evaluation of Dimebon in cellular model of Huntington's disease". Molecular Neurodegeneration. 3 (1): 15. doi:10.1186/1750-1326-3-15. PMC 2577671. PMID 18939977.

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. doi:10.1016/S0163-7258(01)00169-3. PMID 11916537.
  • Thomas DR (Sep 2006). "5-ht5A receptors as a therapeutic target". Pharmacology & Therapeutics. 111 (3): 707–14. doi:10.1016/j.pharmthera.2005.12.006. PMID 16516972.
  • 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. 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". Cytogenetics and Cell Genetics. 72 (2–3): 187–8. doi:10.1159/000134184. PMID 8978771.
  • "Toward a complete human genome sequence". Genome Research. 8 (11): 1097–108. Nov 1998. doi:10.1101/gr.8.11.1097. PMID 9847074.
  • 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. doi:10.1159/000054878. PMID 11287788.
  • 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. doi:10.1038/sj.mp.4000829. PMID 11317225.
  • 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. doi:10.1016/S0014-2999(01)00933-5. PMID 11343685.
  • 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. doi:10.1046/j.1471-4159.2003.01518.x. PMID 12558985.
  • 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. doi:10.1021/jm030080s. PMID 12930153.
  • 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. doi:10.1016/j.molbrainres.2005.04.009. PMID 15921820.

External links

  • "5-ht5a". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
  • Human HTR5A genome location and HTR5A gene details page in the UCSC Genome Browser.

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


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