5-hydroxytryptamine 1A receptor
From DrugPedia: A Wikipedia for Drug discovery
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| - | + | ==Description== | |
| + | '''5-hydroxytryptamine (serotonin) receptor 1A''' is a [[5-HT1 receptor|5-HT<sub>1</sub> receptor]]. | ||
| + | ''HTR1A'' denotes the human [[gene]] encoding it.<ref name="pmid2591972">{{cite journal | author = Gilliam TC, Freimer NB, Kaufmann CA, Powchik PP, Bassett AS, Bengtsson U, Wasmuth JJ | title = Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia | journal = Genomics | volume = 5 | issue = 4 | pages = 940–4 | year = 1989 | month = November | pmid = 2591972 | url = | issn = }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: HTR1A 5-hydroxytryptamine (serotonin) receptor 1A | url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3350 | accessdate = }}</ref> | ||
| + | 5-HT<sub>1A</sub> acts on the [[central nervous system|CNS]], where it induces neuronal inhibition and controls behaviour, such as sleep, feeding, thermoregulation, aggression, anxiety. | ||
==Source Organism== | ==Source Organism== | ||
Canis familiaris (Dog). | Canis familiaris (Dog). | ||
| Line 11: | Line 14: | ||
Belongs to the G-protein coupled receptor 1 family. | Belongs to the G-protein coupled receptor 1 family. | ||
==Post translational Modification== | ==Post translational Modification== | ||
| + | |||
| + | ==Ligands== | ||
| + | The distribution of 5-HT<sub>1A</sub> receptors in the human brain may be imaged with the [[positron emission tomography]] using the [[radioligand]] [<sup>11</sup>C][[WAY-100635]].<ref name="pmid7498295">{{cite journal | ||
| + | | author = Pike VW, McCarron JA, Lammerstma AA, Hume SP, Poole K, Grasby PM, Malizia A, Cliffe IA, Fletcher A, Bench CJ | title = First delineation of 5-HT<sub>1A</sub> receptors in human brain with PET and [<sup>11</sup>C]WAY-100635 | journal = Eur. J. Pharmacol. | volume = 283 | issue = 1-3 | pages = R1–3 | year = 1995 | pmid = 7498295 | doi = 10.1016/0014-2999(95)00438-Q | ||
| + | }}</ref> | ||
| + | For example, one study has found increased 5-HT<sub>1A</sub> binding in type 2 [[diabetes]].<ref name="pmid11814436">{{cite journal | ||
| + | | author = Price JC, Kelley DE, Ryan CM, Meltzer CC, Drevets WC, Mathis CA, Mazumdar S, Reynolds CF | title = Evidence of increased serotonin-1A receptor binding in type 2 diabetes: a positron emission tomography study | journal = Brain Res. | volume = 927 | issue = 1 | pages = 97–103 | year = 2002 | pmid = 11814436 | doi = 10.1016/S0006-8993(01)03297-8 | ||
| + | }}</ref> | ||
| + | Another PET study found a negative correlation between amount of 5-HT<sub>1A</sub> binding in the [[raphe nuclei]], [[hippocampus]] and [[neocortex]] and a self reported tendency to have spiritual experiences.<ref name="pmid14594742">{{cite journal | author = Borg J, Andrée B, Soderstrom H, Farde L | title = The serotonin system and spiritual experiences | journal = Am J Psychiatry | volume = 160 | issue = 11 | pages = 1965–9 | year = 2003 | month = November | pmid = 14594742 | doi = 10.1176/appi.ajp.160.11.1965 | url = }}</ref> | ||
| + | |||
| + | Labeled with [[tritium]], WAY-100635 may also be used in [[autoradiography]].<ref name="pmid9152998">{{cite journal | ||
| + | | author = Burnet PW, Eastwood SL, Harrison PJ | ||
| + | | title = [<sup>3</sup>H]WAY-100635 for 5-HT<sub>1A</sub> receptor autoradiography in human brain: a comparison with [<sup>3</sup>H]8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia | ||
| + | | journal = Neurochem. Int. | ||
| + | | volume = 30 | ||
| + | | issue = 6 | ||
| + | | pages = 565–574 | ||
| + | | year = 1997 | ||
| + | | pmid = 9152998 | ||
| + | | doi = 10.1016/S0197-0186(96)00124-6 | ||
| + | }}</ref> | ||
| + | |||
| + | {| class="wikitable" | ||
| + | ! [[Agonist]]s | ||
| + | ! [[Antagonist]]s | ||
| + | |- | ||
| + | | valign="top" | | ||
| + | *[[buspirone]] | ||
| + | *[[Aripiprazole]] | ||
| + | *[[5-Carboxamidotryptamine|5-CT]] | ||
| + | *[[8-OH-DPAT]] | ||
| + | *[[flesinoxan]] | ||
| + | *[[LSD]] | ||
| + | *[[Methylenedioxymethamphetamine|MDMA]] (speculated)<ref>{{cite journal | author = Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS. | title = A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy"). | url = http://www.mdma.net/oxytocin-release/index.html}}</ref> | ||
| + | *[[psilocin]] | ||
| + | *[[U-92016A]]<ref name="pmid7965808">{{cite journal | author = McCall RB, Romero AG, Bienkowski MJ, Harris DW, McGuire JC, Piercey MF, Shuck ME, Smith MW, Svensson KA, Schreur PJ, et al. | title = Characterization of U-92016A as a selective, orally active, high intrinsic activity 5-hydroxytryptamine<sub>1A</sub> agonist.| journal = J. Pharmacol. Exp. Ther. | volume = 271 | issue = 2 | pages = 875-883 | year = 1994 | pmid = 7965808 | issn = | url = http://jpet.aspetjournals.org/cgi/content/abstract/271/2/875 }}</ref> | ||
| + | *[[vilazodone]] | ||
| + | *[[xaliproden]] | ||
| + | | valign="top" | | ||
| + | *[[ergotamine]] | ||
| + | *[[lecozotan]] | ||
| + | *[[methiothepin]] | ||
| + | *[[MPPF]] | ||
| + | *[[pindolol]] | ||
| + | *[[robalzotan]] | ||
| + | *[[spiperone]] | ||
| + | *[[WAY-100135]] | ||
| + | *[[WAY-100635]]<ref name="pmid8768728">{{cite journal | author = Fornal CA, Metzler CW, Gallegos RA, Veasey SC, McCreary AC, Jacobs BL | title = WAY-100635, a potent and selective 5-hydroxytryptamine<sub>1A</sub> antagonist, increases serotonergic neuronal activity in behaving cats: comparison with (S)-WAY-100135 | journal = J. Pharmacol. Exp. Ther. | volume = 278 | issue = 2 | pages = 752–62 | year = 1996 | pmid = 8768728 | issn = | url = http://jpet.aspetjournals.org/cgi/content/abstract/278/2/752 }}</ref> | ||
| + | *[[yohimbine]] | ||
| + | |- | ||
| + | |} | ||
| + | |||
| + | == Genetics == | ||
| + | The receptor is coded by the ''HTR1A'' [[gene]]. | ||
| + | There are several human [[polymorphism]]s associated with this gene. | ||
| + | A 2007 review listed 27 [[single nucleotide polymorphism]]s (SNP).<ref name="DragoA20075HT1A">{{cite journal | author = Drago A, Ronchi DD, Serretti A | title = 5-HT<sub>1A</sub> gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies | journal = Int. J. Neuropsychopharmacol. | volume = 11 | issue = 5 | pages = 701–21 | year = 2008 | month = August | pmid = 18047755 | doi = 10.1017/S1461145707008218 | url = }}</ref> | ||
| + | The most investigated SNPs are | ||
| + | C(-1019)G ([[rs6295]]) (C-1018G,<ref name="pmid10412191">{{cite journal | author = Wu S, Comings DE | title = A common C-1018G polymorphism in the human 5-HT<sub>1A</sub> receptor gene | journal = Psychiatr. Genet. | volume = 9 | issue = 2 | pages = 105–6 | year = 1999 | month = June | pmid = 10412191 | url = | doi = 10.1097/00041444-199906000-00010 }}</ref> | ||
| + | Ile28Val ([[rs1799921]]), Arg219Leu ([[rs1800044]]) and Gly22Ser ([[rs1799920]]).<ref name="DragoA20075HT1A"/> | ||
| + | Some of the other SNPs are Pro16Leu, Gly272Asp and the [[synonymous polymorphism]] G294A ([[rs6294]]). | ||
| + | |||
| + | The gene variants have been studied in relation to [[psychiatric disorder]]s with no definitive results.<ref name="DragoA20075HT1A"/> | ||
==Function== | ==Function== | ||
| - | This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity (By similarity). | + | This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity (By similarity) |
| + | |||
| + | ==External links== | ||
| + | * {{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2310 | title = 5-HT<sub>1A</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 = }} | ||
| + | |||
| + | ==References== | ||
| + | {{refbegin | 2}} | ||
| + | {{PBB_Further_reading | ||
| + | | citations = | ||
| + | *{{cite journal | author=el Mestikawy S, Fargin A, Raymond JR, ''et al.'' |title=The 5-HT1A receptor: an overview of recent advances |journal=Neurochem. Res. |volume=16 |issue= 1 |pages= 1–10 |year= 1991 |pmid= 2052135 |doi= }} | ||
| + | *{{cite journal | author=Hensler JG |title=Regulation of 5-HT1A receptor function in brain following agonist or antidepressant administration |journal=Life Sci. |volume=72 |issue= 15 |pages= 1665–82 |year= 2003 |pmid= 12559389 |doi= }} | ||
| + | *{{cite journal | author=Van Oekelen D, Luyten WH, Leysen JE |title=5-HT2A and 5-HT2C receptors and their atypical regulation properties |journal=Life Sci. |volume=72 |issue= 22 |pages= 2429–49 |year= 2003 |pmid= 12650852 |doi= }} | ||
| + | *{{cite journal | author=Lesch KP, Gutknecht L |title=Focus on The 5-HT1A receptor: emerging role of a gene regulatory variant in psychopathology and pharmacogenetics |journal=Int. J. Neuropsychopharmacol. |volume=7 |issue= 4 |pages= 381–5 |year= 2005 |pmid= 15683551 |doi= 10.1017/S1461145704004845 }} | ||
| + | *{{cite journal | author=Kalipatnapu S, Chattopadhyay A |title=Membrane protein solubilization: recent advances and challenges in solubilization of serotonin1A receptors |journal=IUBMB Life |volume=57 |issue= 7 |pages= 505–12 |year= 2006 |pmid= 16081372 |doi= 10.1080/15216540500167237 }} | ||
| + | *{{cite journal | author=Varrault A, Bockaert J, Waeber C |title=Activation of 5-HT1A receptors expressed in NIH-3T3 cells induces focus formation and potentiates EGF effect on DNA synthesis |journal=Mol. Biol. Cell |volume=3 |issue= 9 |pages= 961–9 |year= 1992 |pmid= 1330092 |doi= }} | ||
| + | *{{cite journal | author=Levy FO, Gudermann T, Perez-Reyes E, ''et al.'' |title=Molecular cloning of a human serotonin receptor (S12) with a pharmacological profile resembling that of the 5-HT1D subtype |journal=J. Biol. Chem. |volume=267 |issue= 11 |pages= 7553–62 |year= 1992 |pmid= 1559993 |doi= }} | ||
| + | *{{cite journal | author=Melmer G, Sherrington R, Mankoo B, ''et al.'' |title=A cosmid clone for the 5HT1A receptor (HTR1A) reveals a TaqI RFLP that shows tight linkage to dna loci D5S6, D5S39, and D5S76 |journal=Genomics |volume=11 |issue= 3 |pages= 767–9 |year= 1992 |pmid= 1685484 |doi= }} | ||
| + | *{{cite journal | author=Parks CL, Chang LS, Shenk T |title=A polymerase chain reaction mediated by a single primer: cloning of genomic sequences adjacent to a serotonin receptor protein coding region |journal=Nucleic Acids Res. |volume=19 |issue= 25 |pages= 7155–60 |year= 1992 |pmid= 1766875 |doi= }} | ||
| + | *{{cite journal | author=Gilliam TC, Freimer NB, Kaufmann CA, ''et al.'' |title=Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia |journal=Genomics |volume=5 |issue= 4 |pages= 940–4 |year= 1990 |pmid= 2591972 |doi= }} | ||
| + | *{{cite journal | author=Kobilka BK, Frielle T, Collins S, ''et al.'' |title=An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins |journal=Nature |volume=329 |issue= 6134 |pages= 75–9 |year= 1987 |pmid= 3041227 |doi= 10.1038/329075a0 }} | ||
| + | *{{cite journal | author=Fargin A, Raymond JR, Lohse MJ, ''et al.'' |title=The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor |journal=Nature |volume=335 |issue= 6188 |pages= 358–60 |year= 1988 |pmid= 3138543 |doi= 10.1038/335358a0 }} | ||
| + | *{{cite journal | author=Nakhai B, Nielsen DA, Linnoila M, Goldman D |title=Two naturally occurring amino acid substitutions in the human 5-HT1A receptor: glycine 22 to serine 22 and isoleucine 28 to valine 28 |journal=Biochem. Biophys. Res. Commun. |volume=210 |issue= 2 |pages= 530–6 |year= 1995 |pmid= 7755630 |doi= }} | ||
| + | *{{cite journal | author=Aune TM, McGrath KM, Sarr T, ''et al.'' |title=Expression of 5HT1a receptors on activated human T cells. Regulation of cyclic AMP levels and T cell proliferation by 5-hydroxytryptamine |journal=J. Immunol. |volume=151 |issue= 3 |pages= 1175–83 |year= 1993 |pmid= 8393041 |doi= }} | ||
| + | *{{cite journal | author=Parks CL, Shenk T |title=The serotonin 1a receptor gene contains a TATA-less promoter that responds to MAZ and Sp1 |journal=J. Biol. Chem. |volume=271 |issue= 8 |pages= 4417–30 |year= 1996 |pmid= 8626793 |doi= }} | ||
| + | *{{cite journal | author=Stockmeier CA, Shapiro LA, Dilley GE, ''et al.'' |title=Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity |journal=J. Neurosci. |volume=18 |issue= 18 |pages= 7394–401 |year= 1998 |pmid= 9736659 |doi= }} | ||
| + | *{{cite journal | author=Kawanishi Y, Harada S, Tachikawa H, ''et al.'' |title=Novel mutations in the promoter and coding region of the human 5-HT1A receptor gene and association analysis in schizophrenia |journal=Am. J. Med. Genet. |volume=81 |issue= 5 |pages= 434–9 |year= 1998 |pmid= 9754630 |doi= }} | ||
| + | *{{cite journal | author=Salim K, Fenton T, Bacha J, ''et al.'' |title=Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation |journal=J. Biol. Chem. |volume=277 |issue= 18 |pages= 15482–5 |year= 2002 |pmid= 11854302 |doi= 10.1074/jbc.M201539200 }} | ||
| + | }} | ||
| + | {{refend}} | ||
| + | |||
| + | {{NLM content}} | ||
| + | {{transmembranereceptor-stub}} | ||
| + | {{G protein-coupled receptors}} | ||
| + | [[Category:G protein coupled receptors]] | ||
| - | + | <!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. --> | |
| + | {{PBB_Controls | ||
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| + | }} | ||
Revision as of 05:50, 16 February 2009
Contents |
Description
5-hydroxytryptamine (serotonin) receptor 1A is a 5-HT1 receptor. HTR1A denotes the human gene encoding it.<ref name="pmid2591972">Gilliam TC, Freimer NB, Kaufmann CA, Powchik PP, Bassett AS, Bengtsson U, Wasmuth JJ (November 1989). "Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia". Genomics 5 (4): 940–4. PMID 2591972.</ref><ref name="entrez">Template:Cite web</ref> 5-HT1A acts on the CNS, where it induces neuronal inhibition and controls behaviour, such as sleep, feeding, thermoregulation, aggression, anxiety.
Source Organism
Canis familiaris (Dog).
Taxomomy
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;Mammalia; Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae;Canis.
Subcellular Localization
Cell membrane; multi-pass membrane protein.
Developmental Stage
Similarity
Belongs to the G-protein coupled receptor 1 family.
Post translational Modification
Ligands
The distribution of 5-HT1A receptors in the human brain may be imaged with the positron emission tomography using the radioligand [11C]WAY-100635.<ref name="pmid7498295">Pike VW, McCarron JA, Lammerstma AA, Hume SP, Poole K, Grasby PM, Malizia A, Cliffe IA, Fletcher A, Bench CJ (1995). "First delineation of 5-HT1A receptors in human brain with PET and [11C]WAY-100635". Eur. J. Pharmacol. 283 (1-3): R1–3. doi:. PMID 7498295.</ref> For example, one study has found increased 5-HT1A binding in type 2 diabetes.<ref name="pmid11814436">Price JC, Kelley DE, Ryan CM, Meltzer CC, Drevets WC, Mathis CA, Mazumdar S, Reynolds CF (2002). "Evidence of increased serotonin-1A receptor binding in type 2 diabetes: a positron emission tomography study". Brain Res. 927 (1): 97–103. doi:. PMID 11814436.</ref> Another PET study found a negative correlation between amount of 5-HT1A binding in the raphe nuclei, hippocampus and neocortex and a self reported tendency to have spiritual experiences.<ref name="pmid14594742">Borg J, Andrée B, Soderstrom H, Farde L (November 2003). "The serotonin system and spiritual experiences". Am J Psychiatry 160 (11): 1965–9. doi:. PMID 14594742.</ref>
Labeled with tritium, WAY-100635 may also be used in autoradiography.<ref name="pmid9152998">Burnet PW, Eastwood SL, Harrison PJ (1997). "[3H]WAY-100635 for 5-HT1A receptor autoradiography in human brain: a comparison with [3H]8-OH-DPAT and demonstration of increased binding in the frontal cortex in schizophrenia". Neurochem. Int. 30 (6): 565–574. doi:. PMID 9152998.</ref>
Genetics
The receptor is coded by the HTR1A gene. There are several human polymorphisms associated with this gene. A 2007 review listed 27 single nucleotide polymorphisms (SNP).<ref name="DragoA20075HT1A">Drago A, Ronchi DD, Serretti A (August 2008). "5-HT1A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies". Int. J. Neuropsychopharmacol. 11 (5): 701–21. doi:. PMID 18047755.</ref> The most investigated SNPs are C(-1019)G (rs6295) (C-1018G,<ref name="pmid10412191">Wu S, Comings DE (June 1999). "A common C-1018G polymorphism in the human 5-HT1A receptor gene". Psychiatr. Genet. 9 (2): 105–6. doi:. PMID 10412191.</ref> Ile28Val (rs1799921), Arg219Leu (rs1800044) and Gly22Ser (rs1799920).<ref name="DragoA20075HT1A"/> Some of the other SNPs are Pro16Leu, Gly272Asp and the synonymous polymorphism G294A (rs6294).
The gene variants have been studied in relation to psychiatric disorders with no definitive results.<ref name="DragoA20075HT1A"/>
Function
This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity (By similarity)
External links
References
Template:NLM content Template:Transmembranereceptor-stub Template:G protein-coupled receptorsTemplate:PBB Controls
