More information on this family may be found on the IUPHAR-DB family and introduction pages.
Tachykinin receptors (provisional nomenclature, [16]) are activated by the endogenous peptides substance P (SP), neurokinin A (NKA; previously known as substance K, neurokinin α, neuromedin L), neurokinin B (NKB; previously known as neurokinin β, neuromedin K), neuropeptide K and neuropeptide γ (N-terminally extended forms of neurokinin A). The neurokinins (A and B) are mammalian members of the tachykinin family, which includes peptides of mammalian and nonmammalian origin containing the consensus sequence: Phe-x-Gly-Leu-Met. Marked species differences in pharmacology exist for all three receptors, in particular with nonpeptide ligands.
Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Receptors 
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Commons, KG. (2010) Neuronal pathways linking substance P to drug addiction and stress. Brain Res., 1314: 175-82. [PMID:19913520]
Diemunsch, P; Joshi, GP; Brichant, JF. (2009) Neurokinin-1 receptor antagonists in the prevention of postoperative nausea and vomiting. Br J Anaesth, 103 (1): 7-13. [PMID:19454547]
Foord, S. M., Bonner, T. I., Neubig, R. R., Rosser, E. M., Pin, J. P., Davenport, A. P., Spedding, M. and Harmar, A. J. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57: 279-288. [PMID:15914470]
Jones, S; Gibbins, JM. (2008) The neurokinin 1 receptor: a potential new target for anti-platelet therapy?. Curr Opin Pharmacol, 8 (2): 114-9. [PMID:18296119]
Rance, NE; Krajewski, SJ; Smith, MA; Cholanian, M; Dacks, PA. (2010) Neurokinin B and the hypothalamic regulation of reproduction. Brain Res., 1364: 116-28. [PMID:20800582]
Tuluc, F; Lai, JP; Kilpatrick, LE; Evans, DL; Douglas, SD. (2009) Neurokinin 1 receptor isoforms and the control of innate immunity. Trends Immunol., 30 (6): 271-6. [PMID:19427266]
1. Anthes, J. C., Chapman, R. W., Richard, C., Eckel, S., Corboz, M., Hey, J. A., Fernandez, X., Greenfeder, S., McLeod, R., Sehring, S., Rizzo, C., Crawley, Y., Shih, N. Y., Piwinski, J., Reichard, G., Ting, P., Carruthers, N., Cuss, F. M., Billah, M., Kreutner, W. and Egan, R. W. (2002) SCH 206272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist. Eur J Pharmacol, 450: 191-202. [PMID:12206858]
2. Beaujouan, J. C., Saffroy, M., Torrens, Y. and Glowinski, J. (1997) Potency and selectivity of the tachykinin NK3 receptor antagonist SR 142801. Eur J Pharmacol, 319: 307-316. [PMID:9042606]
3. Bellucci, F., Carini, F., Catalani, C., Cucchi, P., Lecci, A., Meini, S., Patacchini, R., Quartara, L., Ricci, R., Tramontana, M., Giuliani, S. and Maggi, C. A. (2002) Pharmacological profile of the novel mammalian tachykinin, hemokinin 1. Br J Pharmacol, 135: 266-274. [PMID:11786503]
4. Bennacef, I., Tymciu, S., Dhilly, M., Lasne, M. C., Debruyne, D., Perrio, C. and Barré, L. (2004) Synthesis and biological evaluation of novel fluoro and iodo quinoline carboxamides as potential ligands of NK-3 receptors for in vivo imaging studies. Bioorg Med Chem, 12: 4533-4541. [PMID:15265501]
5. Beresford, IJ; Sheldrick, RL; Ball, DI; Turpin, MP; Walsh, DM; Hawcock, AB; Coleman, RA; Hagan, RM; Tyers, MB. (1995) GR159897, a potent non-peptide antagonist at tachykinin NK2 receptors. Eur. J. Pharmacol., 272 (2-3): 241-8. [PMID:7713168]
6. Boden, P; Eden, JM; Hodgson, J; Horwell, DC; Hughes, J; McKnight, AT; Lewthwaite, RA; Pritchard, MC; Raphy, J; Meecham, K; et al.. (1996) Use of a dipeptide chemical library in the development of non-peptide tachykinin NK3 receptor selective antagonists. J. Med. Chem., 39 (8): 1664-75. [PMID:8648606]
7. Bradshaw, CG; Ceszkowski, K; Turcatti, G; Beresford, IJ; Chollet, A. (1994) Synthesis and characterization of selective fluorescent ligands for the neurokinin NK2 receptor. J. Med. Chem., 37 (13): 1991-5. [PMID:8027981]
8. Catalioto, RM; Criscuoli, M; Cucchi, P; Giachetti, A; Gianotti, D; Giuliani, S; Lecci, A; Lippi, A; Patacchini, R; Quartara, L; et al.. (1998) MEN 11420 (Nepadutant), a novel glycosylated bicyclic peptide tachykinin NK2 receptor antagonist. Br. J. Pharmacol., 123 (1): 81-91. [PMID:9484857]
9. Chung, FZ; Wu, LH; Tian, Y; Vartanian, MA; Lee, H; Bikker, J; Humblet, C; Pritchard, MC; Raphy, J; Suman-Chauhan, N. (1995) Two classes of structurally different antagonists display similar species preference for the human tachykinin neurokinin3 receptor. Mol. Pharmacol., 48 (4): 711-6. [PMID:7476898]
10. Cialdai, C., Tramontana, M., Patacchini, R., Lecci, A., Catalani, C., Catalioto, R. M., Meini, S., Valenti, C., Altamura, M., Giuliani, S. and Maggi, C. A. (2006) MEN15596, a novel nonpeptide tachykinin NK2 receptor antagonist. Eur J Pharmacol, 549: 140-148. [PMID:16979621]
11. Deal, MJ; Hagan, RM; Ireland, SJ; Jordan, CC; McElroy, AB; Porter, B; Ross, BC; Stephens-Smith, M; Ward, P. (1992) Conformationally constrained tachykinin analogues: potent and highly selective neurokinin NK-2 receptor agonists. J. Med. Chem., 35 (22): 4195-204. [PMID:1331460]
12. Donaldson, LF; Haskell, CA; Hanley, MR. (1996) Functional characterization by heterologous expression of a novel cloned tachykinin peptide receptor. Biochem. J., 320 ( Pt 1): 1-5. [PMID:8947459]
13. Emonds-Alt, X., Golliot, F., Pointeau, P., Le Fur, G. and Breliere, J. C. (1993) Characterization of the binding sites of [3H]SR 48968, a potent nonpeptide radioligand antagonist of the neurokinin-2 receptor. Biochem Biophys Res Commun, 191: 1172-1177. [PMID:7682062]
14. Emonds-Alt, X; Bichon, D; Ducoux, JP; Heaulme, M; Miloux, B; Poncelet, M; Proietto, V; Van Broeck, D; Vilain, P; Neliat, G. (1995) SR 142801, the first potent non-peptide antagonist of the tachykinin NK3 receptor. Life Sci., 56 (1): PL27-32. [PMID:7830490]
15. Fong, TM; Yu, H; Strader, CD. (1992) Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580. J. Biol. Chem., 267 (36): 25668-71. [PMID:1281470]
16. Foord, S. M., Bonner, T. I., Neubig, R. R., Rosser, E. M., Pin, J. P., Davenport, A. P., Spedding, M. and Harmar, A. J. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57: 279-288. [PMID:15914470]
17. Giardina, GA; Sarau, HM; Farina, C; Medhurst, AD; Grugni, M; Foley, JJ; Raveglia, LF; Schmidt, DB; Rigolio, R; Vassallo, M; et al.. (1996) 2-Phenyl-4-quinolinecarboxamides: a novel class of potent and selective non-peptide competitive antagonists for the human neurokinin-3 receptor. J. Med. Chem., 39 (12): 2281-4. [PMID:8691422]
18. Gitter, BD; Bruns, RF; Howbert, JJ; Waters, DC; Threlkeld, PG; Cox, LM; Nixon, JA; Lobb, KL; Mason, NR; Stengel, PW. (1995) Pharmacological characterization of LY303870: a novel, potent and selective nonpeptide substance P (neurokinin-1) receptor antagonist. J. Pharmacol. Exp. Ther., 275 (2): 737-44. [PMID:7473161]
19. Grisshammer, R; Little, J; Aharony, D. (1994) Expression of rat NK-2 (neurokinin A) receptor in E. coli. Recept. Channels, 2 (4): 295-302. [PMID:7719707]
20. Hale, JJ; Mills, SG; MacCoss, M; Finke, PE; Cascieri, MA; Sadowski, S; Ber, E; Chicchi, GG; Kurtz, M; Metzger, J; et al.. (1998) Structural optimization affording 2-(R)-(1-(R)-3, 5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a potent, orally active, long-acting morpholine acetal human NK-1 receptor antagonist. J. Med. Chem., 41 (23): 4607-14. [PMID:9804700]
21. Hastrup, H. and Schwartz, T. W. (1996) Septide and neurokinin A are high-affinity ligands on the NK-1 receptor: evidence from homologous versus heterologous binding analysis. FEBS Lett, 399: 264-266. [PMID:8985159]
22. Huang, SC; Korlipara, VL. (2010) Neurokinin-1 receptor antagonists: a comprehensive patent survey. Expert Opin Ther Pat, 20 (8): 1019-45. [PMID:20533894]
23. Kamali, F. (2001) Osanetant Sanofi-Synthélabo. Curr Opin Investig Drugs, 2: 950-956. [PMID:11757797]
24. Krause, JE; Staveteig, PT; Mentzer, JN; Schmidt, SK; Tucker, JB; Brodbeck, RM; Bu, JY; Karpitskiy, VV. (1997) 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. Proc. Natl. Acad. Sci. U.S.A., 94 (1): 310-5. [PMID:8990205]
25. Matuszek, MA; Zeng, XP; Strigas, J; Burcher, E. (1998) An investigation of tachykinin NK2 receptor subtypes in the rat. Eur. J. Pharmacol., 352 (1): 103-9. [PMID:9718274]
26. Oury-Donat, F; Carayon, P; Thurneyssen, O; Pailhon, V; Emonds-Alt, X; Soubrié, P; Le Fur, G. (1995) Functional characterization of the nonpeptide neurokinin3 (NK3) receptor antagonist, SR142801 on the human NK3 receptor expressed in Chinese hamster ovary cells. J. Pharmacol. Exp. Ther., 274 (1): 148-54. [PMID:7616392]
27. Roush, ED; Kwatra, MM. (1998) Human substance P receptor expressed in Chinese hamster ovary cells directly activates G(alpha q/11), G(alpha s), G(alpha o). FEBS Lett., 428 (3): 291-4. [PMID:9654151]
28. Sarau, H. M., Feild, J. A., Ames, R. S., Foley, J. J., Nuthulaganti, P., Schmidt, D. B., Buckley, P. T., Elshourbagy, N. A., Brawner, M. E., Luttmann, M. A., Giardina, G. A. and Hay, D. W. (2001) Molecular and pharmacological characterization of the murine tachykinin NK(3) receptor. Eur J Pharmacol, 413: 143-150. [PMID:11226387]
29. Sarau, H. M., Griswold, D. E., Potts, W., Foley, J. J., Schmidt, D. B., Webb, E. F., Martin, L. D., Brawner, M. E., Elshourbagy, N. A., Medhurst, A. D., Giardina, G. A. and Hay, D. W. (1997) Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist. J Pharmacol Exp Ther, 281: 1303-1311. [PMID:9190866]
30. Smith, PW; Cooper, AW; Bell, R; Beresford, IJ; Gore, PM; McElroy, AB; Pritchard, JM; Saez, V; Taylor, NR; Sheldrick, RL. (1995) New spiropiperidines as potent and selective non-peptide tachykinin NK2 receptor antagonists. J. Med. Chem., 38 (19): 3772-9. [PMID:7562907]
31. Takeda, Y., Chou, K. B., Takeda, J., Sachais, B. S. and Krause, J. E. (1991) Molecular cloning, structural characterization and functional expression of the human substance P receptor. Biochem Biophys Res Commun, 179: 1232-1240. [PMID:1718267]
32. Tian, Y., Wu, L. H., Oxender, D. L. and Chung, F. Z. (1996) The unpredicted high affinities of a large number of naturally occurring tachykinins for chimeric NK1/NK3 receptors suggest a role for an inhibitory domain in determining receptor specificity. J Biol Chem, 271: 20250-20257. [PMID:8702757]
33. Tousignant, C; Guillemette, G; Drapeau, G; Télémaque, S; Dion, S; Regoli, D. (1990) 125I-BH[Sar9, Met(O2)11]-SP, a new selective ligand for the NK-1 receptor in the central nervous system. Brain Res., 524 (2): 263-70. [PMID:1705465]
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The NK1 receptor has also been described to couple to other G proteins [27]. The hexapeptide agonist septide appears to bind to an overlapping but non-identical site to substance P on the NK1 receptor. There are suggestions for additional subtypes of tachykinin receptor; an orphan receptor (SwissProt P30098) with structural similarities to the NK3 receptor was found to respond to NKB when expressed in Xenopus oocytes or Chinese hamster ovary cells [12,24].