Tachykinin receptor 3 explained

Tachykinin receptor 3, also known as TACR3, is a protein which in humans is encoded by the TACR3 gene.^{[1] [2]}

Function

This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neurokinin 3, also referred to as neurokinin B.

Selective ligands

A number of selective ligands are available for NK₃. NK₃ receptor antagonists are being investigated as treatments for various indications.^[3]

Agonists

• Neurokinin B – endogenous peptide ligand, also interacts with other neurokinin receptors but has highest affinity for NK₃
• Senktide – 7-amino acid polypeptide, NK₃ selective, CAS# 106128-89-6

Antagonists

• Elinzanetant (BAY-3427080 GSK-1144814, NT-814)
• Fezolinetant (ESN-364)
• Osanetant (SR-142,801)
• Pavinetant (MLE-4901, AZD-4901, AZD-2624)
• Talnetant (SB-223,412)
• SB-222,200 – potent and selective antagonist, K_i = 4.4 nM, 3-Methyl-2-phenyl-N-[(1S)-1-phenylpropyl]-4-quinolinecarboxamide, CAS# 174635-69-9
• SB-218,795 – more selective than SB-222,200, K_i = 13 nM, (R)-[(2-Phenyl-4-quinolinylcarbonyl)amino]-methyl ester benzeneacetic acid, CAS# 174635-53-1

See also

• Tachykinin receptor

Further reading

• Khawaja AM, Rogers DF . Tachykinins: receptor to effector . The International Journal of Biochemistry & Cell Biology . 28 . 7 . 721–38 . Jul 1996 . 8925404 . 10.1016/1357-2725(96)00017-9 .
• Advenier C, Lagente V, Boichot E . The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough . The European Respiratory Journal . 10 . 8 . 1892–906 . Aug 1997 . 9272936 . 10.1183/09031936.97.10081892 . free .
• Buell G, Schulz MF, Arkinstall SJ, Maury K, Missotten M, Adami N, Talabot F, Kawashima E . Molecular characterisation, expression and localisation of human neurokinin-3 receptor . FEBS Letters . 299 . 1 . 90–5 . Mar 1992 . 1312036 . 10.1016/0014-5793(92)80107-R . 29031625 . free .
• Takahashi K, Tanaka A, Hara M, Nakanishi S . The primary structure and gene organization of human substance P and neuromedin K receptors . European Journal of Biochemistry . 204 . 3 . 1025–33 . Mar 1992 . 1312928 . 10.1111/j.1432-1033.1992.tb16724.x .
• Xie GX, Miyajima A, Goldstein A . Expression cloning of cDNA encoding a seven-helix receptor from human placenta with affinity for opioid ligands . Proceedings of the National Academy of Sciences of the United States of America . 89 . 9 . 4124–8 . May 1992 . 1315051 . 525645 . 10.1073/pnas.89.9.4124 . 1992PNAS...89.4124X . free .
• Huang RR, Cheung AH, Mazina KE, Strader CD, Fong TM . cDNA sequence and heterologous expression of the human neurokinin-3 receptor . Biochemical and Biophysical Research Communications . 184 . 2 . 966–72 . Apr 1992 . 1374246 . 10.1016/0006-291X(92)90685-E .
• Dion S, Corcos J, Carmel M, Drapeau G, Regoli D . Substance P and neurokinins as stimulants of the human isolated urinary bladder . Neuropeptides . 11 . 2 . 83–7 . 1988 . 2452993 . 10.1016/0143-4179(88)90015-7 . 13728584 .
• Krause JE, Staveteig PT, Mentzer JN, Schmidt SK, Tucker JB, Brodbeck RM, Bu JY, Karpitskiy VV . Functional expression of a novel human neurokinin-3 receptor homolog that binds [3H]senktide and [125I-MePhe7]neurokinin B, and is responsive to tachykinin peptide agonists . Proceedings of the National Academy of Sciences of the United States of America . 94 . 1 . 310–5 . Jan 1997 . 8990205 . 19326 . 10.1073/pnas.94.1.310 . 1997PNAS...94..310K . free .
• Brunelleschi S, Bordin G, Colangelo D, Viano I . Tachykinin receptors on human monocytes: their involvement in rheumatoid arthritis . Neuropeptides . 32 . 3 . 215–23 . Jun 1998 . 10189055 . 10.1016/S0143-4179(98)90040-3 . 40222022 .
• Page NM, Woods RJ, Gardiner SM, Lomthaisong K, Gladwell RT, Butlin DJ, Manyonda IT, Lowry PJ . Excessive placental secretion of neurokinin B during the third trimester causes pre-eclampsia . Nature . 405 . 6788 . 797–800 . Jun 2000 . 10866201 . 10.1038/35015579 . 2000Natur.405..797P . 4392048 .
• Bellucci F, Carini F, Catalani C, Cucchi P, Lecci A, Meini S, Patacchini R, Quartara L, Ricci R, Tramontana M, Giuliani S, Maggi CA . Pharmacological profile of the novel mammalian tachykinin, hemokinin 1 . British Journal of Pharmacology . 135 . 1 . 266–74 . Jan 2002 . 11786503 . 1573107 . 10.1038/sj.bjp.0704443 .
• Graham GJ, Stevens JM, Page NM, Grant AD, Brain SD, Lowry PJ, Gibbins JM . Tachykinins regulate the function of platelets . Blood . 104 . 4 . 1058–65 . Aug 2004 . 15130944 . 10.1182/blood-2003-11-3979 . free .
• Page NM, Dakour J, Morrish DW . Gene regulation of neurokinin B and its receptor NK3 in late pregnancy and pre-eclampsia . Molecular Human Reproduction . 12 . 7 . 427–33 . Jul 2006 . 16709596 . 10.1093/molehr/gal025 .

External links

• Web site: Tachykinin Receptors: NK₃ . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-09 . 2012-05-31 . https://web.archive.org/web/20120531105011/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3031 . dead .

Notes and References

1. Huang RR, Cheung AH, Mazina KE, Strader CD, Fong TM . cDNA sequence and heterologous expression of the human neurokinin-3 receptor . Biochemical and Biophysical Research Communications . 184 . 2 . 966–72 . Apr 1992 . 1374246 . 10.1016/0006-291X(92)90685-E .
2. Web site: Entrez Gene: TACR3 tachykinin receptor 3.
3. Quartara L, Altamura M . Tachykinin receptors antagonists: from research to clinic . Current Drug Targets . 7 . 8 . 975–92 . Aug 2006 . 16918326 . 10.2174/138945006778019381 .