5-hydroxytryptamine receptor 5A

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==Description==
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'''5-hydroxytryptamine (serotonin) receptor 5A''', also known as '''HTR5A''', is a [[protein]] which in humans is encoded by the ''HTR5A'' [[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><ref name="pmid7988681">{{cite journal | author = 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 Lett. | volume = 355 | issue = 3 | pages = 242–6 | year = 1994 | month = December | pmid = 7988681 | doi = 10.1016/0014-5793(94)01209-1 | url = h| issn = }}</ref>
==Source Organism==
==Source Organism==
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==Function==
==Function==
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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 | author = 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 = Eur. J. Pharmacol. | volume = 361 | issue = 2-3 | pages = 299–309 | year = 1998 | month = November | pmid = 9865521 | doi = | url = | issn = }}</ref> This protein has been shown to function in part through the regulation of intracellular Ca<sup>2+</sup> mobilization.<ref name="entrez"/>
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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 | author = 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 = Mol. Pharmacol. | volume = 43 | issue = 3 | pages = 313–9 | year = 1993 | month = March | pmid = 8450829 | doi = | url = http://molpharm.aspetjournals.org/cgi/reprint/43/3/313 | issn = }}</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 | author = Nelson DL | title = 5-HT5 receptors | journal = Curr Drug Targets CNS Neurol Disord | volume = 3 | issue = 1 | pages = 53–8 | year = 2004 | month = February | pmid = 14965244 | doi = | url = | issn = }}</ref>
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==Clinical signficance==
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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"/>
[[Categories:Receptors]]
[[Categories:Receptors]]
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{{Wrongtitle|title=5-HT<sub>5A</sub> receptor}}
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{{PBB|geneid=3361}}
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==Ligands==
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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 | author = Wesołowska A | title = In the search for selective ligands of 5-HT5, 5-HT6 and 5-HT7 serotonin receptors | journal = Pol J Pharmacol | 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 | issn = }}</ref><ref name="pmid18023344">{{cite journal | author = 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 = Bioorg. Med. Chem. Lett. | volume = 18 | issue = 1 | pages = 262–6 | year = 2008 | month = January | pmid = 18023344 | doi = 10.1016/j.bmcl.2007.10.078 | url = | issn = }}</ref>
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<b>Agonists</b>
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* [[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 | 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 | month = August | pmid = 15921820 | doi = 10.1016/j.molbrainres.2005.04.009 | url = | issn = }}</ref>
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* Another ligand which 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" >{{Citation
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| inventor-last = Garcia-Ladona
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| inventor-first = Francisco Javier
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| inventor2-last = Szabo
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| inventor2-first = Laszlo
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| inventor3-last = Steiner
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| inventor3-first = Gerd
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| inventor4-last = Hofmann
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| inventor4-first = Hans-Peter
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| publication-date = 2004-06-15
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| title = Use of 5-HT5-ligands in the treatment of neurodegenerative and neuropsychiatric disturbances
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| country-code = US
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| patent-number = 6750221
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}}</ref>
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[[Image:DE19900637A1_5HT5A_ligand.png|200px]]
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===Antagonists===
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* [[SB-699,551]]
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==See also==
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* [[5-HT receptor]]
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==References==
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{{reflist}}
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==External links==
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* {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2331 | title = 5-ht<sub>5a</sub>  | accessdate = | author = | authorlink = | coauthors = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | language = | archiveurl = | archivedate = | quote = }}
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==Further reading==
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{{refbegin | 2}}
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{{PBB_Further_reading
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| citations =
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*{{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=  }}
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*{{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 }}
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*{{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=  }}
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*{{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=  }}
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*{{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=  }}
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*{{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=  }}
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*{{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=  }}
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*{{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 }}
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*{{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=  }}
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*{{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 }}
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*{{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=  }}
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*{{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 }}
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*{{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 }}
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*{{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 }}
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*{{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 }}
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*{{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 }}
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*{{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 }}
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}}
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{{refend}}
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{{NLM content}}
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{{transmembranereceptor-stub}}
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{{G protein-coupled receptors}}
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[[Category:G protein coupled receptors]]
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Revision as of 06:11, 16 February 2009

Contents

Description

5-hydroxytryptamine (serotonin) receptor 5A, also known as HTR5A, is a protein which in humans is encoded by the HTR5A gene.<ref name="entrez">Template:Cite web</ref><ref name="pmid7988681">Rees S, den Daas I, Foord S, Goodson S, Bull D, Kilpatrick G, Lee M (December 1994). "[h 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. </ref>

Source Organism

Cavia porcellus (Guinea pig).

Taxomomy

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia;Hystricognathi; Caviidae; Cavia.

Subcellular Localization

Membrane (By similarity).

Developmental Stage

Similarity

Belongs to the G-protein coupled receptor 1 family.

Post translational Modification

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.<ref name="pmid9865521">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. PMID 9865521. </ref> This protein has been shown to function in part through the regulation of intracellular Ca2+ mobilization.<ref name="entrez"/>

Rodents have been shown to possess two functional 5-HT5 receptor subtypes, 5-HT5A and 5-HT5B,<ref name="pmid8450829">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. </ref> 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.<ref name="pmid14965244">Nelson DL (February 2004). "5-HT5 receptors". Curr Drug Targets CNS Neurol Disord 3 (1): 53–8. PMID 14965244. </ref>

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.<ref name="entrez"/>


Categories:Receptors Template:Wrongtitle Template:PBB


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.<ref name="pmid12523486">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. </ref><ref name="pmid18023344">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. </ref>

Agonists

  • Valerenic acid, a component of valerian, has been shown to act as a 5HT5A partial agonist.<ref name="pmid15921820">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. </ref>
  • Another ligand which has been recently disclosed is shown below, claimed be a selective 5-HT5A agonist with Ki = 124 nM.<ref name = "US6750221" >Template:Citation</ref>

Image:DE19900637A1 5HT5A ligand.png

Antagonists

See also

References

Unknown extension tag "references"

External links

Further reading

Template:PBB Further reading

Template:NLM content Template:Transmembranereceptor-stub Template:G protein-coupled receptorsTemplate:PBB Controls

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