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Gene Review

Tacr1  -  tachykinin receptor 1

Mus musculus

Synonyms: NK-1 receptor, NK-1R, NK1 receptor, NK1-R, Nk1r, ...
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Disease relevance of Tacr1


Psychiatry related information on Tacr1


High impact information on Tacr1

  • The substance P receptor is highly expressed in areas of the brain that are implicated in these behaviours, but also in other areas such as the nucleus accumbens which mediate the motivational properties of both natural rewards such as food and of drugs of abuse such as opiates [8].
  • Administration of a specific substance P-receptor antagonist (CP-96,345) reduced toxin A-induced intestinal fluid secretion and inhibited neutrophil infiltration in normal, mast cell-deficient KitW/KitW-v, and mast cell-reconstituted KitW/KitW-v mice [9].
  • We speculate that mesenteric fat depots may participate in intestinal inflammatory responses via SP-NK-1R-related pathways, as well as other systemic responses to the presence of an ongoing inflammation of the colon [10].
  • Intracolonic administration of trinitrobenzene sulfonic acid in mice causes inflammation in the colon that is accompanied by increased expression of proinflammatory cytokines and of the substance P (SP), neurokinin 1 receptor (NK-1R) in the proximal mesenteric fat depot [10].
  • To study interneuron function in the basal ganglia, we tested and characterized an NK-1 receptor-based method for targeted ablation of specific classes of interneuron in the striatum [11].

Chemical compound and disease context of Tacr1


Biological context of Tacr1


Anatomical context of Tacr1

  • Interleukin 12 (IL-12) also induced strong T-cell SPr expression [2].
  • Antigen-sensitized NK-1R(-/-) mice also exhibit bladder mast cell degranulation in response to antigen challenge [5].
  • The results provide evidence that kinin receptors participate in NK1 receptor-dependent neutrophil accumulation in inflamed mouse skin [20].
  • The NK1 receptor localizes to the plasma membrane microdomains, and its activation is dependent on lipid raft integrity [21].
  • 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 [21].

Associations of Tacr1 with chemical compounds

  • The results support the concept that NK1 agonists such as substance P cannot act on their own to mediate neutrophil accumulation in naive skin and provide direct evidence that in inflamed skin, under certain circumstances, the NK1 receptor can play a pivotal role in modulating neutrophil accumulation during the ongoing inflammatory process [20].
  • The carrageenin (500 microg)-induced response was inhibited (p < 0.05) by a NK1 receptor antagonist, SR140333 (480 nmol/kg i.v. at -5 min), in the wild-type group [20].
  • Here we have further examined this role by comparing the behavioural responses to intradermal capsaicin of mutant mice with a disruption of the NK1 receptor (NK1 KO) and wild-type (WT) mice [22].
  • Neurokinin B induces oedema formation in mouse lung via tachykinin receptor-independent mechanisms [23].
  • Furthermore, contractions induced by trypsin and SLIGRL were reduced by neurokinin receptor NK1 antagonist SR-140333 or NK2 antagonist SR-48968 alone or were further reduced by combined application of SR-140333 and SR-48968, indicating the involvement of neurokinin receptors [24].

Physical interactions of Tacr1


Co-localisations of Tacr1


Regulatory relationships of Tacr1


Other interactions of Tacr1

  • SR48968, NK2 receptor antagonist, but not SR140333, NK1 receptor antagonist, decreased the tone only in mdx gastric preparations [27].
  • IL-12 induces SPr independently of TCR activation and IFN-gamma expression [2].
  • We conclude that NKB is a potent stimulator of plasma extravasation through two distinct pathways: via activation of NK(1) receptors, and via a novel neurokinin receptor-independent pathway specific to NKB that operates in the mouse lung [23].
  • However, T cells cultured with IL-12 and IL-10 did not express NK-1R [28].
  • We determined whether genetic deletion of the NK1-R reduces mortality and, conversely, whether genetic deletion of NEP increases mortality in a lethal model of hemorrhagic pancreatitis [29].

Analytical, diagnostic and therapeutic context of Tacr1


  1. The NK1 receptor mediates both the hyperalgesia and the resistance to morphine in mice lacking noradrenaline. Jasmin, L., Tien, D., Weinshenker, D., Palmiter, R.D., Green, P.G., Janni, G., Ohara, P.T. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. Interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni. Blum, A.M., Metwali, A., Crawford, C., Li, J., Qadir, K., Elliott, D.E., Weinstock, J.V. FASEB J. (2001) [Pubmed]
  3. Substance P modulates antigen-induced, IFN-gamma production in murine Schistosomiasis mansoni. Blum, A.M., Metwali, A., Cook, G., Mathew, R.C., Elliott, D., Weinstock, J.V. J. Immunol. (1993) [Pubmed]
  4. Neurokinin 1 receptor signaling affects the local innate immune defense against genital herpes virus infection. Svensson, A., Kaim, J., Mallard, C., Olsson, A., Brodin, E., Hökfelt, T., Eriksson, K. J. Immunol. (2005) [Pubmed]
  5. Neurokinin-1 (NK-1) receptor is required in antigen-induced cystitis. Saban, R., Saban, M.R., Nguyen, N.B., Lu, B., Gerard, C., Gerard, N.P., Hammond, T.G. Am. J. Pathol. (2000) [Pubmed]
  6. Behavioral and physiologic effects of genetic or pharmacologic inactivation of the substance P receptor (NK1). Santarelli, L., Gobbi, G., Blier, P., Hen, R. The Journal of clinical psychiatry. (2002) [Pubmed]
  7. The progesterone derivative dydrogesterone down-regulates neurokinin 1 receptor expression on lymphocytes, induces a Th2 skew and exerts hypoalgesic effects in mice. Orsal, A.S., Blois, S., Labuz, D., Peters, E.M., Schaefer, M., Arck, P.C. J. Mol. Med. (2006) [Pubmed]
  8. Rewarding effects of opiates are absent in mice lacking the receptor for substance P. Murtra, P., Sheasby, A.M., Hunt, S.P., De Felipe, C. Nature (2000) [Pubmed]
  9. Direct evidence of mast cell involvement in Clostridium difficile toxin A-induced enteritis in mice. Wershil, B.K., Castagliuolo, I., Pothoulakis, C. Gastroenterology (1998) [Pubmed]
  10. Induction of colitis causes inflammatory responses in fat depots: evidence for substance P pathways in human mesenteric preadipocytes. Karagiannides, I., Kokkotou, E., Tansky, M., Tchkonia, T., Giorgadze, N., O'Brien, M., Leeman, S.E., Kirkland, J.L., Pothoulakis, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Local circuit neurons in the striatum regulate neural and behavioral responses to dopaminergic stimulation. Saka, E., Iadarola, M., Fitzgerald, D.J., Graybiel, A.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  12. Neurokinin-1 receptor antagonists CP-96,345 and L-733,060 protect mice from cytokine-mediated liver injury. Bang, R., Sass, G., Kiemer, A.K., Vollmar, A.M., Neuhuber, W.L., Tiegs, G. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  13. Cutaneous allergic contact dermatitis responses are diminished in mice deficient in neurokinin 1 receptors and augmented by neurokinin 2 receptor blockage. Scholzen, T.E., Steinhoff, M., Sindrilaru, A., Schwarz, A., Bunnett, N.W., Luger, T.A., Armstrong, C.A., Ansel, J.C. FASEB J. (2004) [Pubmed]
  14. Neurokinin-1 (NK-1) receptor antagonists abrogate methamphetamine-induced striatal dopaminergic neurotoxicity in the murine brain. Yu, J., Cadet, J.L., Angulo, J.A. J. Neurochem. (2002) [Pubmed]
  15. Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis. Nathan, J.D., Patel, A.A., McVey, D.C., Thomas, J.E., Prpic, V., Vigna, S.R., Liddle, R.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2001) [Pubmed]
  16. Spantide I Decreases Type I Cytokines, Enhances IL-10, and Reduces Corneal Perforation in Susceptible Mice after Pseudomonas aeruginosa Infection. Hazlett, L.D., McClellan, S.A., Barrett, R.P., Liu, J., Zhang, Y., Lighvani, S. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  17. Mast cell deficient and neurokinin-1 receptor knockout mice are protected from stress-induced hair growth inhibition. Arck, P.C., Handjiski, B., Kuhlmei, A., Peters, E.M., Knackstedt, M., Peter, A., Hunt, S.P., Klapp, B.F., Paus, R. J. Mol. Med. (2005) [Pubmed]
  18. Formalin- or adjuvant-induced peripheral inflammation increases neurokinin-1 receptor gene expression in the mouse. Allen, A.L., Cortright, D.N., McCarson, K.E. Brain Res. (2003) [Pubmed]
  19. Antiinflammatory and analgesic activity of a non-peptide substance P receptor antagonist. Nagahisa, A., Kanai, Y., Suga, O., Taniguchi, K., Tsuchiya, M., Lowe, J.A., Hess, H.J. Eur. J. Pharmacol. (1992) [Pubmed]
  20. Neurokinin-1 receptor agonists are involved in mediating neutrophil accumulation in the inflamed, but not normal, cutaneous microvasculature: an in vivo study using neurokinin-1 receptor knockout mice. Cao, T., Pintér, E., Al-Rashed, S., Gerard, N., Hoult, J.R., Brain, S.D. J. Immunol. (2000) [Pubmed]
  21. 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]
  22. Role of central and peripheral tachykinin NK1 receptors in capsaicin-induced pain and hyperalgesia in mice. Laird, J.M., Roza, C., De Felipe, C., Hunt, S.P., Cervero, F. Pain (2001) [Pubmed]
  23. Neurokinin B induces oedema formation in mouse lung via tachykinin receptor-independent mechanisms. Grant, A.D., Akhtar, R., Gerard, N.P., Brain, S.D. J. Physiol. (Lond.) (2002) [Pubmed]
  24. PAR-2 agonists induce contraction of murine small intestine through neurokinin receptors. Zhao, A., Shea-Donohue, T. Am. J. Physiol. Gastrointest. Liver Physiol. (2003) [Pubmed]
  25. Expression of the NK-1 receptor on islet cells and invading immune cells in the non-obese diabetic mouse. Persson-Sjögren, S., Lejon, K., Holmberg, D., Forsgren, S. J. Autoimmun. (2005) [Pubmed]
  26. IL-18 and IL-12 signal through the NF-kappa B pathway to induce NK-1R expression on T cells. Weinstock, J.V., Blum, A., Metwali, A., Elliott, D., Arsenescu, R. J. Immunol. (2003) [Pubmed]
  27. Altered tachykinergic influence on gastric mechanical activity in mdx mice. Mulè, F., Amato, A., Vannucchi, M.G., Faussone-Pellegrini, M.S., Serio, R. Neurogastroenterol. Motil. (2006) [Pubmed]
  28. Substance P regulates Th1-type colitis in IL-10 knockout mice. Weinstock, J.V., Blum, A., Metwali, A., Elliott, D., Bunnett, N., Arsenescu, R. J. Immunol. (2003) [Pubmed]
  29. Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice. Maa, J., Grady, E.F., Yoshimi, S.K., Drasin, T.E., Kim, E.H., Hutter, M.M., Bunnett, N.W., Kirkwood, K.S. Surgery (2000) [Pubmed]
  30. Increased formation of corpora lutea in neurokinin 1-receptor deficient mice. Löffler, S., Schulz, A., Hunt, S.P., Spanel-Borowski, K. Mol. Reprod. Dev. (2004) [Pubmed]
  31. Effects of central administration of tachykinin receptor agonists and antagonists on plus-maze behavior in mice. Teixeira, R.M., Santos, A.R., Ribeiro, S.J., Calixto, J.B., Rae, G.A., De Lima, T.C. Eur. J. Pharmacol. (1996) [Pubmed]
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