Biology:Tachykinin receptor 2

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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

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

• "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. doi:10.1016/0016-5085(92)91787-5. PMID 1370160. 
• "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 (1): 389–90. 1991. doi:10.1111/j.1749-6632.1991.tb33132.x. PMID 1659296. Bibcode: 1991NYASA.632..389G. 
• "Cloning, expression of the human substance K receptor, and analysis of its role in mitogenesis". Annals of the New York Academy of Sciences 632 (1): 426–7. 1991. doi:10.1111/j.1749-6632.1991.tb33144.x. PMID 1659297. Bibcode: 1991NYASA.632..426C. 
• "Human NK-2 receptor gene maps to chromosome region 10q11-21". Human Genetics 88 (2): 200–3. Dec 1991. doi:10.1007/bf00206072. PMID 1661704. 
• "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. doi:10.1016/0006-291X(91)91940-E. PMID 1710456. 
• "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. doi:10.1016/S0021-9258(17)35323-1. PMID 1845990. 
• "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. doi:10.1111/j.1749-6632.1991.tb33144.x. PMID 1848773. Bibcode: 1991NYASA.632..426C. 
• "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. doi:10.1016/S0021-9258(17)30526-4. PMID 2173708. 
• "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. doi:10.1074/jbc.270.15.8944. PMID 7721803. 
• "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. doi:10.1016/S0021-9258(18)46979-7. PMID 7961636. 
• "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. doi:10.1016/0014-5793(94)80119-3. PMID 8307161. 
• "Tachykinin receptors on human monocytes: their involvement in rheumatoid arthritis". Neuropeptides 32 (3): 215–23. Jun 1998. doi:10.1016/S0143-4179(98)90040-3. PMID 10189055. 
• "Effect of nepadutant at tachykinin NK(2) receptors in human intestine and urinary bladder". European Journal of Pharmacology 398 (3): 389–97. Jun 2000. doi:10.1016/S0014-2999(00)00346-0. PMID 10862829. 
• "Pharmacological profile of the novel mammalian tachykinin, hemokinin 1". British Journal of Pharmacology 135 (1): 266–74. Jan 2002. doi:10.1038/sj.bjp.0704443. PMID 11786503. 
• "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. doi:10.1038/sj.bjp.0704650. PMID 11906947. 
• "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. doi:10.1016/S0024-3205(02)02240-3. PMID 12427486. 
• "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. doi:10.1016/S0165-5728(03)00096-1. PMID 12742655. 
• "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. doi:10.1152/ajpgi.00064.2003. PMID 12801882. 

External links

• "Tachykinin Receptors: NK₂". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=3030. 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.