View source for Tachykinin receptor 1

{{Mergefrom|NK1 receptor antagonist#The neurokinin-1 receptor|date=January 2009}}
{{PBB|geneid=6869}}
The '''tachykinin receptor 1''' ('''TACR1''') also known as '''neurokinin 1 receptor''' ('''NK1R''') or '''substance P receptor''' ('''SPR''') is a [[G protein coupled receptor]] found in the [[central nervous system]] and [[peripheral nervous system]].  The [[endogenous]] [[ligand]] for this receptor is [[Substance P]], although it has some affinity for other [[tachykinin]]s.  The protein is the product of the ''TACR1'' [[gene]].<ref name="pmid1718267">{{cite journal | author = Takeda Y, Chou KB, Takeda J, Sachais BS, Krause JE | title = Molecular cloning, structural characterization and functional expression of the human substance P receptor | journal = Biochem. Biophys. Res. Commun. | volume = 179 | issue = 3 | pages = 1232–40 | year = 1991 | pmid = 1718267 | doi = 10.1016/0006-291X(91)91704-G }}</ref>

== Clinical significance ==
This receptor is considered an attractive [[medication|drug]] [[Biological target|target]], particularly with regards to potential [[analgesic]]s and [[anti-depressant]]s.<ref name="pmid12871173">{{cite journal | author = Humphrey JM | title = Medicinal chemistry of selective neurokinin-1 antagonists | journal = Current topics in medicinal chemistry | volume = 3 | issue = 12 | pages = 1423–35 | year = 2003 | pmid = 12871173 | doi = 10.2174/1568026033451925 }}</ref><ref name="pmid19129399">{{cite journal |author=Yu YJ, Arttamangkul S, Evans CJ, Williams JT, von Zastrow M |title=Neurokinin 1 receptors regulate morphine-induced endocytosis and desensitization of mu-opioid receptors in CNS neurons |journal=The Journal of Neuroscience : the Official Journal of the Society for Neuroscience |volume=29 |issue=1 |pages=222–33 |year=2009 |month=January |pmid=19129399 |doi=10.1523/JNEUROSCI.4315-08.2009 |url= |pmc=2775560}}</ref> It was identified as a candidate in the etiology of [[bipolar disorder]] by a 2008 study.<ref name="pmid18180429">{{cite journal | author = Perlis RH, Purcell S, Fagerness J, Kirby A, Petryshen TL, Fan J, Sklar P | title = Family-based association study of lithium-related and other candidate genes in bipolar disorder | journal = Arch. Gen. Psychiatry | volume = 65 | issue = 1 | pages = 53–61 | year = 2008 | month = January | pmid = 18180429 | doi = 10.1001/archgenpsychiatry.2007.15 | url =  }}</ref> Furthermore TACR1 antagonists have shown promise for the treatment in alcoholism.<ref name="pmid18276852">{{cite journal | author = George DT, Gilman J, Hersh J, Thorsell A, Herion D, Geyer C, Peng X, Kielbasa W, Rawlings R, Brandt JE, Gehlert DR, Tauscher JT, Hunt SP, Hommer D, Heilig M | title = Neurokinin 1 receptor antagonism as a possible therapy for alcoholism | journal = Science (journal) | volume = 319 | issue = 5869 | pages = 1536–9 | year = 2008 | month = March | pmid = 18276852 | doi = 10.1126/science.1153813 | url =  }}</ref> Finally TACR1 antagonists may also have a role as novel [[antiemetic]]s.<ref name="pmid16514255">{{cite journal | author = Jordan K | title = Neurokinin-1-receptor antagonists: a new approach in antiemetic therapy | journal = Onkologie | volume = 29 | issue = 1-2 | pages = 39–43 | year = 2006 | pmid = 16514255 | doi = 10.1159/000089800 }}</ref>

==Selective ligands==
Many selective ligands for NK<sub>1</sub> are now available, several of which have gone into clinical use as [[antiemetics]].

===Agonists===
* GR-73632 - potent and selective agonist, EC<sub>50</sub> 2nM, 5-amino acid polypeptide chain. CAS# 133156-06-6

===Antagonists===
* [[Aprepitant]] 
* [[Casopitant]] 
* Ezlopitant
* [[Fosaprepitant]] 
* Lanepitant
* [[Maropitant]] 
* [[Vestipitant]]
* [[L-733,060]] 
* L-741,671
* L-742,694
* RP-67580 - potent and selective antagonist, Ki 2.9nM, (3aR,7aR)-Octahydro-2-[1-imino-2-(2-methoxyphenyl)ethyl ]-7,7-diphenyl-4H-isoindol, CAS# 135911-02-3
* RPR-100,893
* CP-96345 
* CP-99994
* GR-205,171 
* TAK-637
* T-2328

==See also==
* [[NK1 receptor antagonist]]
* [[Tachykinin receptor]]
* [[Discovery and development of neurokinin 1 receptor antagonists]]

== References ==
{{Reflist}}

==Further reading==
{{refbegin | 2}}
{{PBB Further reading 
| citations = 
*{{cite journal  | author=Burcher E |title=The study of tachykinin receptors. |journal=Clin. Exp. Pharmacol. Physiol. |volume=16 |issue= 6 |pages= 539–43 |year= 1989 |pmid= 2548782 |doi=10.1111/j.1440-1681.1989.tb01602.x  }}
*{{cite journal  | author=Kowall NW, Quigley BJ, Krause JE, ''et al.'' |title=Substance P and substance P receptor histochemistry in human neurodegenerative diseases. |journal=Regul. Pept. |volume=46 |issue= 1-2 |pages= 174–85 |year= 1993 |pmid= 7692486 |doi=10.1016/0167-0115(93)90028-7  }}
*{{cite journal  | author=Patacchini R, Maggi CA |title=Peripheral tachykinin receptors as targets for new drugs. |journal=Eur. J. Pharmacol. |volume=429 |issue= 1-3 |pages= 13–21 |year= 2002 |pmid= 11698023 |doi=10.1016/S0014-2999(01)01301-2  }}
*{{cite journal  | author=Saito R, Takano Y, Kamiya HO |title=Roles of substance P and NK(1) receptor in the brainstem in the development of emesis. |journal=J. Pharmacol. Sci. |volume=91 |issue= 2 |pages= 87–94 |year= 2003 |pmid= 12686752 |doi=10.1254/jphs.91.87  }}
*{{cite journal  | author=Fong TM, Yu H, Huang RR, Strader CD |title=The extracellular domain of the neurokinin-1 receptor is required for high-affinity binding of peptides. |journal=Biochemistry |volume=31 |issue= 47 |pages= 11806–11 |year= 1992 |pmid= 1280161 |doi=10.1021/bi00162a019  }}
*{{cite journal  | author=Fong TM, Huang RR, Strader CD |title=Localization of agonist and antagonist binding domains of the human neurokinin-1 receptor. |journal=J. Biol. Chem. |volume=267 |issue= 36 |pages= 25664–7 |year= 1993 |pmid= 1281469 |doi=  }}
*{{cite journal  | author=Fong TM, Anderson SA, Yu H, ''et al.'' |title=Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor. |journal=Mol. Pharmacol. |volume=41 |issue= 1 |pages= 24–30 |year= 1992 |pmid= 1310144 |doi=  }}
*{{cite journal  | author=Takahashi K, Tanaka A, Hara M, Nakanishi S |title=The primary structure and gene organization of human substance P and neuromedin K receptors. |journal=Eur. J. Biochem. |volume=204 |issue= 3 |pages= 1025–33 |year= 1992 |pmid= 1312928 |doi=10.1111/j.1432-1033.1992.tb16724.x  }}
*{{cite journal  | author=Walsh DA, Mapp PI, Wharton J, ''et al.'' |title=Localisation and characterisation of substance P binding to human synovial tissue in rheumatoid arthritis. |journal=Ann. Rheum. Dis. |volume=51 |issue= 3 |pages= 313–7 |year= 1992 |pmid= 1374227 |doi=10.1136/ard.51.3.313  | pmc=1004650  }}
*{{cite journal  | author=Gerard NP, Garraway LA, Eddy RL, ''et al.'' |title=Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones. |journal=Biochemistry |volume=30 |issue= 44 |pages= 10640–6 |year= 1991 |pmid= 1657150 |doi=10.1021/bi00108a006  }}
*{{cite journal  | author=Hopkins B, Powell SJ, Danks P, ''et al.'' |title=Isolation and characterisation of the human lung NK-1 receptor cDNA. |journal=Biochem. Biophys. Res. Commun. |volume=180 |issue= 2 |pages= 1110–7 |year= 1991 |pmid= 1659396 |doi=10.1016/S0006-291X(05)81181-7  }}
*{{cite journal  | author=Takeda Y, Chou KB, Takeda J, ''et al.'' |title=Molecular cloning, structural characterization and functional expression of the human substance P receptor. |journal=Biochem. Biophys. Res. Commun. |volume=179 |issue= 3 |pages= 1232–40 |year= 1991 |pmid= 1718267 |doi=10.1016/0006-291X(91)91704-G  }}
*{{cite journal  | author=Giuliani S, Barbanti G, Turini D, ''et al.'' |title=NK2 tachykinin receptors and contraction of circular muscle of the human colon: characterization of the NK2 receptor subtype. |journal=Eur. J. Pharmacol. |volume=203 |issue= 3 |pages= 365–70 |year= 1992 |pmid= 1723045 |doi=10.1016/0014-2999(91)90892-T  }}
*{{cite journal  | author=Ichinose H, Katoh S, Sueoka T, ''et al.'' |title=Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis. |journal=Biochem. Biophys. Res. Commun. |volume=179 |issue= 1 |pages= 183–9 |year= 1991 |pmid= 1883349 |doi=10.1016/0006-291X(91)91352-D  }}
*{{cite journal  | author=Thöny B, Heizmann CW, Mattei MG |title=Human GTP-cyclohydrolase I gene and sepiapterin reductase gene map to region 14q21-q22 and 2p14-p12, respectively, by in situ hybridization. |journal=Genomics |volume=26 |issue= 1 |pages= 168–70 |year= 1995 |pmid= 7782081 |doi=10.1016/0888-7543(95)80101-Q  }}
*{{cite journal  | author=Fong TM, Cascieri MA, Yu H, ''et al.'' |title=Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345. |journal=Nature |volume=362 |issue= 6418 |pages= 350–3 |year= 1993 |pmid= 8384323 |doi= 10.1038/362350a0 }}
*{{cite journal  | author=Derocq JM, Ségui M, Blazy C, ''et al.'' |title=Effect of substance P on cytokine production by human astrocytic cells and blood mononuclear cells: characterization of novel tachykinin receptor antagonists. |journal=FEBS Lett. |volume=399 |issue= 3 |pages= 321–5 |year= 1997 |pmid= 8985172 |doi=10.1016/S0014-5793(96)01346-4  }}
*{{cite journal  | author=De Felipe C, Herrero JF, O'Brien JA, ''et al.'' |title=Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. |journal=Nature |volume=392 |issue= 6674 |pages= 394–7 |year= 1998 |pmid= 9537323 |doi= 10.1038/32904 }}
}}
{{refend}}

==External links==
*{{cite web | url = http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3029 | title = Tachykinin Receptors: NK<sub>1</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 = }}
* {{MeshName|Receptors,+Neurokinin-1}}

{{G protein-coupled receptors}}
{{Neuropeptide receptors}}
{{Obsessive–compulsive disorder}}

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[[Category:G protein coupled receptors]]
[[Category:Molecular neuroscience]]
[[Category:Biology of bipolar disorder]]


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[[Category:2Fix]]