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Gene Review

TACR1  -  tachykinin receptor 1

Homo sapiens

Synonyms: NK-1 receptor, NK-1R, NK1R, NKIR, SPR, ...
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Disease relevance of TACR1


Psychiatry related information on TACR1


High impact information on TACR1


Chemical compound and disease context of TACR1


Biological context of TACR1


Anatomical context of TACR1

  • The NK1 receptor was transiently expressed in HEK293 and HepG2 cell lines and its localization in membrane microdomains investigated using biochemical methods and immunofluorescent labeling [23].
  • Neurokinin 1 receptor (NK1R) is expressed in central and peripheral nervous system as well as in endothelial and smooth muscle cells and involved in mediation of pain, inflammation, exocrine secretion, and smooth muscle contraction [23].
  • The NK1 receptor localizes to the plasma membrane microdomains, and its activation is dependent on lipid raft integrity [23].
  • We show that the NK1 receptor, similar to the earlier described beta(2)-adrenergic receptor and G proteins, localizes to lipid rafts and caveolae [23].
  • When transfected into COS-7 cells, the NK-1 receptor binds 125I-BHSP with a Kd of 0.35 +/- 0.07 nM and mediates substance P induced phosphatidylinositol metabolism [20].

Associations of TACR1 with chemical compounds

  • 4. The NK1 receptor selective agonist, [Sar9]SP sulphone (10 nM) evoked a maximal facilitatory action on cholinergic responses of 334.9 +/- 63% (P < 0.01) (pD2 = 8.5 +/- 0.06) an effect which was blocked by the selective NK1-receptor antagonist, CP 96,345 (100 nM) (P < 0.05) but not by the NK2 receptor antagonist, MEN 10,376 (100 nM) [24].
  • The human NK-1 receptor transfected in Chinese hamster ovary (CHO) cells was studied with use of different tachykinin analogs: Substance P, [Pro9]SP, [Sar9, Met(O2)11]SP, [Gly9 psi (CH2CH2) Leu10]SP, Ac-Arg-septide, septide, [Gly9 psi (CH2CH2) Gly10]SP, NKA, [pGlu6]SP(6-11) and [Lys5]NKA(4-10) [25].
  • All these data indicated that SR 140333 blocked SP-induced cytokine production in U373MG astrocytic cells via a specific NK1 receptor-mediated process [26].
  • The effects of NKA and eledoisin were blocked by the NK2 receptor antagonist SR 48968 but not by the NK1 receptor antagonist SR 140333 in tissues from both groups of women [27].
  • Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist [28].

Physical interactions of TACR1

  • The NK-2 receptor-selective compound SR 48,968 was found to bind with low affinity to the human NK-1 receptor but with 15-fold even lower affinity to the rat receptor [29].
  • These results suggest that the tachykinin-induced inward current is mediated through the NK1 receptor which mainly couples to PTX-insensitive G-protein in bullfrog primary afferent neurons [30].
  • Finally, we show here that the amyloid-beta peptide competes for binding to the SEC receptor but does not bind to the substance P receptor, therein raising the possibility that the SEC receptor is involved in certain biological activities, including the recently described neurotrophic and neurotoxic effects ascribed to the amyloid-beta peptide [31].
  • These data suggest that the pharmacological properties of [125I]L-703606 binding to the human NK1 receptor are similar to those of antagonists of nonpeptide guanine nucleotide-binding protein-coupled receptors and that this ligand will be useful for the biochemical and pharmacological characterization of the human NK1 receptor [32].

Regulatory relationships of TACR1

  • The stimulatory effects on BM progenitors mediated by NK-1R can be partly inhibited by NK-2R activation [33].
  • Highly selective non-peptide (CP96,345) or peptide (GR82,334) NK1 receptor antagonists were more effective in antagonizing septide-(IC50's 0.2 +/- 0.06 nM and 70 +/- 18 nM) than SP-(IC50's 6.7 +/- 1.3 nM and 1.95 +/- 0.4 microM) induced IL-6 secretion [34].
  • These data support the existence, also in human U373 MG cells, of a septide-sensitive NK1 receptor subtype(s) and/or epitope(s) blocked with high affinity by NK1 antagonist [34].
  • These results suggest that IL 2 stimulates B cells via a low-affinity interaction with a receptor different from the Tac receptor identified on T cells, and that the active site on the IL 2 molecule for B cells differs from that for T cell targets [35].
  • However, the signalling mechanisms by which SP-NK-1R interaction induces NF-kappaB activation and IL-8 expression are still not clear [36].

Other interactions of TACR1

  • Binding experiments with [3H][Pro9]SP discriminated two classes of peptides with either high affinity (K iota in the nanomolar range) for the human NK-1 receptor or with low affinity (K iota in the micromolar range); this second group of peptides included NKA and [pGlu6]SP(6-11) [25].
  • Agonist treatment induced a stronger intracellular calcium ([Ca2+]i) increase after activation of NK-1R compared to NK-3R, a result that we verified by calcium imaging [37].
  • The contractile response to capsaicin obtained in the presence of the three tachykinin receptor antagonists could be due to the co-released CGRP and/or to other unknown neurotransmitters [38].
  • SU5402 and TGF-beta1 had no effect on the basal level of short NK1R mRNA [39].
  • We report here that human monocytic/macrophage THP-1 cells express the neurokinin 1 receptor (NK-1R), and that exposure of these cells to the proinflammatory cytokine IL-1 beta increased the expression of the NK-1R gene at the mRNA and protein levels [19].

Analytical, diagnostic and therapeutic context of TACR1


  1. Substance P (NK1)- and neurokinin A (NK2)-receptor gene expression in inflammatory airway diseases. Bai, T.R., Zhou, D., Weir, T., Walker, B., Hegele, R., Hayashi, S., McKay, K., Bondy, G.P., Fong, T. Am. J. Physiol. (1995) [Pubmed]
  2. Molecular cloning, structural characterization and functional expression of the human substance P receptor. Takeda, Y., Chou, K.B., Takeda, J., Sachais, B.S., Krause, J.E. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  3. Substance P and substance P receptor histochemistry in human neurodegenerative diseases. Kowall, N.W., Quigley, B.J., Krause, J.E., Lu, F., Kosofsky, B.E., Ferrante, R.J. Regul. Pept. (1993) [Pubmed]
  4. Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease. Mantyh, C.R., Gates, T.S., Zimmerman, R.P., Welton, M.L., Passaro, E.P., Vigna, S.R., Maggio, J.E., Kruger, L., Mantyh, P.W. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  5. Substance P (neurokinin-1) and neurokinin A (neurokinin-2) receptor gene and protein expression in the healthy and inflamed human intestine. Renzi, D., Pellegrini, B., Tonelli, F., Surrenti, C., Calabrò, A. Am. J. Pathol. (2000) [Pubmed]
  6. Fine mapping of the 2p11 dyslexia locus and exclusion of TACR1 as a candidate gene. Peyrard-Janvid, M., Anthoni, H., Onkamo, P., Lahermo, P., Zucchelli, M., Kaminen, N., Hannula-Jouppi, K., Nopola-Hemmi, J., Voutilainen, A., Lyytinen, H., Kere, J. Hum. Genet. (2004) [Pubmed]
  7. An NK1 receptor antagonist affects the circadian regulation of locomotor activity in golden hamsters. Challet, E., Naylor, E., Metzger, J.M., MacIntyre, D.E., Turek, F.W. Brain Res. (1998) [Pubmed]
  8. Mutagenesis and knockout models: NK1 and substance P. Bilkei-Gorzo, A., Zimmer, A. Handbook of experimental pharmacology. (2005) [Pubmed]
  9. Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo. Furmark, T., Appel, L., Michelgård, A., Wahlstedt, K., Ahs, F., Zancan, S., Jacobsson, E., Flyckt, K., Grohp, M., Bergström, M., Pich, E.M., Nilsson, L.G., Bani, M., Långström, B., Fredrikson, M. Biol. Psychiatry (2005) [Pubmed]
  10. Effects of the neuropeptide substance P on sleep, mood, and neuroendocrine measures in healthy young men. Lieb, K., Ahlvers, K., Dancker, K., Strohbusch, S., Reincke, M., Feige, B., Berger, M., Riemann, D., Voderholzer, U. Neuropsychopharmacology (2002) [Pubmed]
  11. Different binding epitopes on the NK1 receptor for substance P and non-peptide antagonist. Gether, U., Johansen, T.E., Snider, R.M., Lowe, J.A., Nakanishi, S., Schwartz, T.W. Nature (1993) [Pubmed]
  12. Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Malmberg, A.B., Yaksh, T.L. Science (1992) [Pubmed]
  13. The binding site of NK receptors on HLA-C molecules. Mandelboim, O., Reyburn, H.T., Sheu, E.G., Vales-Gomez, M., Davis, D.M., Pazmany, L., Strominger, J.L. Immunity (1997) [Pubmed]
  14. Tachykinins and neuropsychiatric disorders. Chahl, L.A. Current drug targets. (2006) [Pubmed]
  15. Use of an NK1 receptor antagonist to prevent delayed emesis after cisplatin. Kris, M.G., Radford, J.E., Pizzo, B.A., Inabinet, R., Hesketh, A., Hesketh, P.J. J. Natl. Cancer Inst. (1997) [Pubmed]
  16. The substance P receptor antagonist CP-99,994 reduces acute postoperative pain. Dionne, R.A., Max, M.B., Gordon, S.M., Parada, S., Sang, C., Gracely, R.H., Sethna, N.F., MacLean, D.B. Clin. Pharmacol. Ther. (1998) [Pubmed]
  17. Critical evaluation of the streptozotocin model of painful diabetic neuropathy in the rat. Fox, A., Eastwood, C., Gentry, C., Manning, D., Urban, L. Pain (1999) [Pubmed]
  18. SR 140333, a novel, selective, and potent nonpeptide antagonist of the NK1 tachykinin receptor: characterization on the U373MG cell line. Oury-Donat, F., Lefevre, I.A., Thurneyssen, O., Gauthier, T., Bordey, A., Feltz, P., Emonds-Alt, X., Le Fur, G., Soubrie, P. J. Neurochem. (1994) [Pubmed]
  19. Regulation of the NK-1 receptor gene expression in human macrophage cells via an NF-kappa B site on its promoter. Simeonidis, S., Castagliuolo, I., Pan, A., Liu, J., Wang, C.C., Mykoniatis, A., Pasha, A., Valenick, L., Sougioultzis, S., Zhao, D., Pothoulakis, C. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  20. Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones. Gerard, N.P., Garraway, L.A., Eddy, R.L., Shows, T.B., Iijima, H., Paquet, J.L., Gerard, C. Biochemistry (1991) [Pubmed]
  21. Human substance P receptor undergoes agonist-dependent phosphorylation by G protein-coupled receptor kinase 5 in vitro. Warabi, K., Richardson, M.D., Barry, W.T., Yamaguchi, K., Roush, E.D., Nishimura, K., Kwatra, M.M. FEBS Lett. (2002) [Pubmed]
  22. The primary structure and gene organization of human substance P and neuromedin K receptors. Takahashi, K., Tanaka, A., Hara, M., Nakanishi, S. Eur. J. Biochem. (1992) [Pubmed]
  23. The NK1 receptor localizes to the plasma membrane microdomains, and its activation is dependent on lipid raft integrity. Monastyrskaya, K., Hostettler, A., Buergi, S., Draeger, A. J. Biol. Chem. (2005) [Pubmed]
  24. Facilitatory effects of selective agonists for tachykinin receptors on cholinergic neurotransmission: evidence for species differences. Belvisi, M.G., Patacchini, R., Barnes, P.J., Maggi, C.A. Br. J. Pharmacol. (1994) [Pubmed]
  25. Tachykinin peptides affect differently the second messenger pathways after binding to CHO-expressed human NK-1 receptors. Sagan, S., Chassaing, G., Pradier, L., Lavielle, S. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  26. Effect of substance P on cytokine production by human astrocytic cells and blood mononuclear cells: characterization of novel tachykinin receptor antagonists. Derocq, J.M., Ségui, M., Blazy, C., Emonds-Alt, X., Le Fur, G., Brelire, J.C., Casellas, P. FEBS Lett. (1996) [Pubmed]
  27. Regulation of the stimulant actions of neurokinin a and human hemokinin-1 on the human uterus: a comparison with histamine. Pennefather, J.N., Patak, E., Ziccone, S., Lilley, A., Pinto, F.M., Page, N.M., Story, M.E., Grover, S., Candenas, M.L. Biol. Reprod. (2006) [Pubmed]
  28. Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist. 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., Hay, D.W. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  29. The species selectivity of chemically distinct tachykinin nonpeptide antagonists is dependent on common divergent residues of the rat and human neurokinin-1 receptors. Jensen, C.J., Gerard, N.P., Schwartz, T.W., Gether, U. Mol. Pharmacol. (1994) [Pubmed]
  30. Tachykinins cause inward current through NK1 receptors in bullfrog sensory neurons. Akasu, T., Ishimatsu, M., Yamada, K. Brain Res. (1996) [Pubmed]
  31. Amyloid-beta peptide, substance P, and bombesin bind to the serpin-enzyme complex receptor. Joslin, G., Krause, J.E., Hershey, A.D., Adams, S.P., Fallon, R.J., Perlmutter, D.H. J. Biol. Chem. (1991) [Pubmed]
  32. Characterization of the binding of a potent, selective, radioiodinated antagonist to the human neurokinin-1 receptor. Cascieri, M.A., Ber, E., Fong, T.M., Sadowski, S., Bansal, A., Swain, C., Seward, E., Frances, B., Burns, D., Strader, C.D. Mol. Pharmacol. (1992) [Pubmed]
  33. Hematopoietic modulation by the tachykinins. Rameshwar, P., Gascón, P. Acta Haematol. (1997) [Pubmed]
  34. Different susceptibility to neurokinin 1 receptor antagonists of substance P and septide-induced interleukin-6 release from U373 MG human astrocytoma cell line. Palma, C., Goso, C., Manzini, S. Neurosci. Lett. (1994) [Pubmed]
  35. Stimulation of immunoglobulin secretion in human B lymphocytes as a direct effect of high concentrations of IL 2. Ralph, P., Jeong, G., Welte, K., Mertelsmann, R., Rabin, H., Henderson, L.E., Souza, L.M., Boone, T.C., Robb, R.J. J. Immunol. (1984) [Pubmed]
  36. Substance P-stimulated interleukin-8 expression in human colonic epithelial cells involves Rho family small GTPases. Zhao, D., Kuhnt-Moore, S., Zeng, H., Pan, A., Wu, J.S., Simeonidis, S., Moyer, M.P., Pothoulakis, C. Biochem. J. (2002) [Pubmed]
  37. Coexpression of preprotachykinin A and B transcripts in the bovine corpus luteum and evidence for functional neurokinin receptor activity in luteal endothelial cells and ovarian macrophages. Brylla, E., Aust, G., Geyer, M., Uckermann, O., Löffler, S., Spanel-Borowski, K. Regul. Pept. (2005) [Pubmed]
  38. Involvement of endogenous tachykinins and CGRP in the motor responses produced by capsaicin in the guinea-pig common bile duct. Patacchini, R., Barthó, L., De Giorgio, R., Lénárd, L., Stanghellini, V., Barbara, G., Lecci, A., Maggi, C.A. Naunyn Schmiedebergs Arch. Pharmacol. (1999) [Pubmed]
  39. Regulation of neurokinin-1 receptor messenger RNA expression in synovial fibroblasts of patients with rheumatoid arthritis. Akasaka, Y., Abe, K., Sato, T., Inoue, H. Neuropeptides (2005) [Pubmed]
  40. Isolation and characterisation of the human lung NK-1 receptor cDNA. Hopkins, B., Powell, S.J., Danks, P., Briggs, I., Graham, A. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  41. Vascular NK-1 receptor occurrence in normal and chronic painful Achilles and patellar tendons: studies on chemically unfixed as well as fixed specimens. Forsgren, S., Danielson, P., Alfredson, H. Regul. Pept. (2005) [Pubmed]
  42. Substance P stimulates inhibitory synaptic transmission in the guinea pig basolateral amygdala in vitro. Maubach, K.A., Martin, K., Smith, D.W., Hewson, L., Frankshun, R.A., Harrison, T., Seabrook, G.R. Neuropharmacology (2001) [Pubmed]
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