Tachykinin receptor 2 explained

Substance-K receptor is a protein that in humans is encoded by the TACR2 gene.^[1]

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 neuropeptide substance K, also referred to as neurokinin A.

Selective Ligands

Several selective ligands for NK₂ are now available, and although most of the compounds developed so far are peptides, one small-molecule antagonist Saredutant is currently in clinical trials as an anxiolytic and antidepressant.

Agonists

• GR-64349 - potent and selective agonist, EC₅₀ 3.7nM, 7-amino acid polypeptide chain. CAS# 137593-52-3

Antagonists

• Ibodutant - failed its Phase 3 trial for IBS treatment in 2015, and abandoned by Menarini
• Saredutant - mixed but mostly negative Phase 3 trial results in 2009, and abandoned by Sanofi-Aventis
  • GR-159897 MEN-10376 - potent and selective antagonist, 7-amino acid polypeptide chain. CAS# 135306-85-3

See also

• Tachykinin receptor

Further reading

• Maggi CA, Giuliani S, Patacchini R, Santicioli P, Theodorsson E, Barbanti G, Turini D, Giachetti A . Tachykinin antagonists inhibit nerve-mediated contractions in the circular muscle of the human ileum. Involvement of neurokinin-2 receptors . Gastroenterology . 102 . 1 . 88–96 . Jan 1992 . 1370160 . 10.1016/0016-5085(92)91787-5.
• Gerard NP, Gerard C . Molecular cloning of the human neurokinin-2 receptor cDNA by polymerase chain reaction and isolation of the gene . Annals of the New York Academy of Sciences . 632 . 389–90 . 1991 . 1 . 1659296 . 10.1111/j.1749-6632.1991.tb33132.x . 1991NYASA.632..389G . 41610315 .
• Cyr C, South V, Saltzman A, Felder S, Ricca GA, Jaye M, Huebner K, Kagan J, Croce CM, Schlessinger J . Cloning, expression of the human substance K receptor, and analysis of its role in mitogenesis . Annals of the New York Academy of Sciences . 632 . 426–7 . 1991 . 1 . 1659297 . 10.1111/j.1749-6632.1991.tb33144.x . 1991NYASA.632..426C . 42849825 .
• Morten JE, Hopkins B, Powell SJ, Graham A . Human NK-2 receptor gene maps to chromosome region 10q11-21 . Human Genetics . 88 . 2 . 200–3 . Dec 1991 . 1661704 . 10.1007/bf00206072 . 328872 .
• Graham A, Hopkins B, Powell SJ, Danks P, Briggs I . Isolation and characterisation of the human lung NK-2 receptor gene using rapid amplification of cDNA ends . Biochemical and Biophysical Research Communications . 177 . 1 . 8–16 . May 1991 . 1710456 . 10.1016/0006-291X(91)91940-E .
• Gerard NP, Eddy RL, Shows TB, Gerard C . The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of the cDNA from tracheal and gastric tissues . The Journal of Biological Chemistry . 266 . 2 . 1354 . Jan 1991 . 10.1016/S0021-9258(17)35323-1 . 1845990 . free .
• Kris RM, South V, Saltzman A, Felder S, Ricca GA, Jaye M, Huebner K, Kagan J, Croce CM, Schlessinger J . Cloning and expression of the human substance K receptor and analysis of its role in mitogenesis . Cell Growth & Differentiation . 2 . 1 . 15–22 . Jan 1991 . 10.1111/j.1749-6632.1991.tb33144.x . 1848773 . 1991NYASA.632..426C . 42849825 .
• Gerard NP, Eddy RL, Shows TB, Gerard C . The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of cDNA from tracheal and gastric tissues . The Journal of Biological Chemistry . 265 . 33 . 20455–62 . Nov 1990 . 10.1016/S0021-9258(17)30526-4 . 2173708 . free .
• Alblas J, van Etten I, Khanum A, Moolenaar WH . C-terminal truncation of the neurokinin-2 receptor causes enhanced and sustained agonist-induced signaling. Role of receptor phosphorylation in signal attenuation . The Journal of Biological Chemistry . 270 . 15 . 8944–51 . Apr 1995 . 7721803 . 10.1074/jbc.270.15.8944 . free .
• Bhogal N, Donnelly D, Findlay JB . The ligand binding site of the neurokinin 2 receptor. Site-directed mutagenesis and identification of neurokinin A binding residues in the human neurokinin 2 receptor . The Journal of Biological Chemistry . 269 . 44 . 27269–74 . Nov 1994 . 10.1016/S0021-9258(18)46979-7 . 7961636 . free .
• Arkinstall S, Emergy I, Church D, Chollet A, Kawashima E . Calcium influx and protein kinase C alpha activation mediate arachidonic acid mobilization by the human NK-2 receptor expressed in Chinese hamster ovary cells . FEBS Letters . 338 . 1 . 75–80 . Jan 1994 . 8307161 . 10.1016/0014-5793(94)80119-3 . 20900006 . 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 .
• Patacchini R, Giuliani S, Turini A, Navarra G, Maggi CA . Effect of nepadutant at tachykinin NK(2) receptors in human intestine and urinary bladder . European Journal of Pharmacology . 398 . 3 . 389–97 . Jun 2000 . 10862829 . 10.1016/S0014-2999(00)00346-0 .
• 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 .
• Patacchini R, Barbagli G, Palminteri E, Lazzeri M, Turini D, Maggi CA . Tachykinin NK1 and NK2 receptors mediate inhibitory vs excitatory motor responses in human isolated corpus cavernosum and spongiosum . British Journal of Pharmacology . 135 . 6 . 1351–4 . Mar 2002 . 11906947 . 1573278 . 10.1038/sj.bjp.0704650 .
• Candenas ML, Cintado CG, Pennefather JN, Pereda MT, Loizaga JM, Maggi CA, Pinto FM . Identification of a tachykinin NK(2) receptor splice variant and its expression in human and rat tissues . Life Sciences . 72 . 3 . 269–77 . Dec 2002 . 12427486 . 10.1016/S0024-3205(02)02240-3 .
• Bandari PS, Qian J, Oh HS, Potian JA, Yehia G, Harrison JS, Rameshwar P . Crosstalk between neurokinin receptors is relevant to hematopoietic regulation: cloning and characterization of neurokinin-2 promoter . Journal of Neuroimmunology . 138 . 1–2 . 65–75 . May 2003 . 12742655 . 10.1016/S0165-5728(03)00096-1 . 3108613 .
• Zhao A, Shea-Donohue T . PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors . American Journal of Physiology. Gastrointestinal and Liver Physiology . 285 . 4 . G696-703 . Oct 2003 . 12801882 . 10.1152/ajpgi.00064.2003 .

External links

• Web site: Tachykinin Receptors: NK₂ . 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/20120531104951/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3030 . dead .

Notes and References

1. Web site: Entrez Gene: TACR2 tachykinin receptor 2.