Tachykinin receptor 1
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Location (UCSC) | Chr 2: 75.05 – 75.2 Mb | Chr 6: 82.38 – 82.54 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
The tachykinin receptor 1 (TACR1) also known as neurokinin 1 receptor (NK1R) or substance P receptor (SPR) is a
Properties
Tachykinins are a family of
Tachykinin NK1 receptor
Distribution and function
The NK1 receptor can be found in both the central and peripheral nervous system. It is present in neurons, brainstem, vascular endothelial cells, muscle, gastrointestinal tracts, genitourinary tract, pulmonary tissue, thyroid gland and different types of immune cells.[9][12][8][10] The binding of SP to the NK1 receptor has been associated with the transmission of stress signals and pain, the contraction of smooth muscles and inflammation.[13] NK1 receptor antagonists have also been studied in migraine, emesis and psychiatric disorders. In fact, aprepitant has been proved effective in a number of pathophysiological models of anxiety and depression.[14] Other diseases in which the NK1 receptor system is involved include asthma, rheumatoid arthritis and gastrointestinal disorders.[15]
Mechanism
SP is synthesized by neurons and transported to
In combination therapy, NK1 receptor antagonists appear to offer better control of delayed emesis and post-operative emesis than drug therapy without NK1 receptor antagonists. NK1 receptor antagonists block responses to a broader range of emetic stimuli than the established 5-HT3 antagonist treatments.[15] It has been reported that centrally-acting NK1 receptors antagonists, such as CP-99994, inhibit emesis induced by apomorphine and loperimidine, which are two compounds that act through central mechanisms.[12]
Clinical significance
This receptor is considered an attractive
Ligands
Many selective ligands for NK1 are now available, several of which have gone into clinical use as
Agonists
- GR-73632 - potent and selective agonist, EC50 2nM, 5-amino acid polypeptide chain. CAS# 133156-06-6
Antagonists
- Aprepitant
- Casopitant
- Elinzanetant
- 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/Vofopitant
- TAK-637
- T-2328
See also
- NK1 receptor antagonist
- Tachykinin receptor
- Discovery and development of neurokinin 1 receptor antagonists
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000115353 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030043 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 1718267.
- ^ S2CID 14975995.
- ^ S2CID 23094292.
- ^ PMID 14754378.
- ^ PMID 16918325.
- ^ PMID 15279567.
- PMID 32119470. Retrieved 28 January 2023.
- ^ PMID 10443564.
- PMID 15713411.
- PMID 16918326.
- ^ PMID 12871173.
- S2CID 13735836.
- PMID 12871173.
- PMID 15155133.
- S2CID 16533561.
- PMID 18180429.
- S2CID 3048287.
- PMID 26844312.
- S2CID 34016787.
Further reading
- Burcher E (June 1989). "The study of tachykinin receptors". Clinical and Experimental Pharmacology & Physiology. 16 (6): 539–543. S2CID 30578296.
- Kowall NW, Quigley BJ, Krause JE, Lu F, Kosofsky BE, Ferrante RJ (July 1993). "Substance P and substance P receptor histochemistry in human neurodegenerative diseases". Regulatory Peptides. 46 (1–2): 174–185. S2CID 54379670.
- Patacchini R, Maggi CA (October 2001). "Peripheral tachykinin receptors as targets for new drugs". European Journal of Pharmacology. 429 (1–3): 13–21. PMID 11698023.
- Saito R, Takano Y, Kamiya HO (February 2003). "Roles of substance P and NK(1) receptor in the brainstem in the development of emesis". Journal of Pharmacological Sciences. 91 (2): 87–94. PMID 12686752.
- Fong TM, Yu H, Huang RR, Strader CD (December 1992). "The extracellular domain of the neurokinin-1 receptor is required for high-affinity binding of peptides". Biochemistry. 31 (47): 11806–11811. PMID 1280161.
- Fong TM, Huang RR, Strader CD (December 1992). "Localization of agonist and antagonist binding domains of the human neurokinin-1 receptor". The Journal of Biological Chemistry. 267 (36): 25664–25667. PMID 1281469.
- Fong TM, Anderson SA, Yu H, Huang RR, Strader CD (January 1992). "Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor". Molecular Pharmacology. 41 (1): 24–30. PMID 1310144.
- Takahashi K, Tanaka A, Hara M, Nakanishi S (March 1992). "The primary structure and gene organization of human substance P and neuromedin K receptors". European Journal of Biochemistry. 204 (3): 1025–1033. PMID 1312928.
- Walsh DA, Mapp PI, Wharton J, Rutherford RA, Kidd BL, Revell PA, et al. (March 1992). "Localisation and characterisation of substance P binding to human synovial tissue in rheumatoid arthritis". Annals of the Rheumatic Diseases. 51 (3): 313–317. PMID 1374227.
- Gerard NP, Garraway LA, Eddy RL, Shows TB, Iijima H, Paquet JL, Gerard C (November 1991). "Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones". Biochemistry. 30 (44): 10640–10646. PMID 1657150.
- Hopkins B, Powell SJ, Danks P, Briggs I, Graham A (October 1991). "Isolation and characterisation of the human lung NK-1 receptor cDNA". Biochemical and Biophysical Research Communications. 180 (2): 1110–1117. PMID 1659396.
- Takeda Y, Chou KB, Takeda J, Sachais BS, Krause JE (September 1991). "Molecular cloning, structural characterization and functional expression of the human substance P receptor". Biochemical and Biophysical Research Communications. 179 (3): 1232–1240. PMID 1718267.
- Giuliani S, Barbanti G, Turini D, Quartara L, Rovero P, Giachetti A, Maggi CA (October 1991). "NK2 tachykinin receptors and contraction of circular muscle of the human colon: characterization of the NK2 receptor subtype". European Journal of Pharmacology. 203 (3): 365–370. PMID 1723045.
- Ichinose H, Katoh S, Sueoka T, Titani K, Fujita K, Nagatsu T (August 1991). "Cloning and sequencing of cDNA encoding human sepiapterin reductase--an enzyme involved in tetrahydrobiopterin biosynthesis". Biochemical and Biophysical Research Communications. 179 (1): 183–189. PMID 1883349.
- Thöny B, Heizmann CW, Mattei MG (March 1995). "Human GTP-cyclohydrolase I gene and sepiapterin reductase gene map to region 14q21-q22 and 2p14-p12, respectively, by in situ hybridization". Genomics. 26 (1): 168–170. PMID 7782081.
- Fong TM, Cascieri MA, Yu H, Bansal A, Swain C, Strader CD (March 1993). "Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345". Nature. 362 (6418): 350–353. S2CID 4339311.
- Derocq JM, Ségui M, Blazy C, Emonds-Alt X, Le Fur G, Brelire JC, Casellas P (December 1996). "Effect of substance P on cytokine production by human astrocytic cells and blood mononuclear cells: characterization of novel tachykinin receptor antagonists". FEBS Letters. 399 (3): 321–325. S2CID 84912440.
- De Felipe C, Herrero JF, O'Brien JA, Palmer JA, Doyle CA, Smith AJ, et al. (March 1998). "Altered nociception, analgesia and aggression in mice lacking the receptor for substance P". Nature. 392 (6674): 394–397. S2CID 4324247.
External links
- "Tachykinin Receptors: NK1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2011-05-16. Retrieved 2007-10-25.
- Receptors,+Neurokinin-1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Overview of all the structural information available in the PDB for UniProt: P25103 (Substance-P receptor) at the PDBe-KB.