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Gene Review

Tac2  -  tachykinin 2

Mus musculus

Synonyms: Neurokinin B-like protein Zneurok1, Nknb, PPT-B, Preprotachykinin-B, Tac3, ...
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Disease relevance of Tac2

  • Cutaneous allergic contact dermatitis responses are diminished in mice deficient in neurokinin 1 receptors and augmented by neurokinin 2 receptor blockage [1].
  • These findings are in keeping with a role for NKB in mediating plasma extravasation in diseases such as pre-eclampsia [2].
  • Several observations suggest that tachykinins (substance P, neurokinin A and neurokinin B) are involved in the pathogenesis of pulmonary diseases and elicit several airway responses such as bronchoconstriction and neurogenic inflammation via interactions with specific receptors denoted NK(1), NK(2) and NK(3) [3].
  • Thus whereas behavioral hypersensitivity after injury is preserved in ppt-A -/- mice, our results suggest that the magnitude and duration of these behavioral responses would be reduced in the absence of SP and/or NKA [4].
  • OBJECTIVE: The present study was designed to examine the effects of allergen sensitization and challenge on the SP/NKA expression in the jugular-nodose ganglion neurons innervating the murine airways [5].

Psychiatry related information on Tac2

  • The effects of intracerebroventricular injections of the neurokinin-2 (NK-2) receptor agonist neurokinin A and the neurokinin-3 (NK-3) receptor agonist senktide on scopolamine (sc)-induced amnesia were investigated based on spontaneous alternation performance in mice [6].

High impact information on Tac2

  • Neurogenic inflammation, which results from peripheral release of substance P and neurokinin A, is almost absent in the mutant mice [7].
  • Thus, the behavioral manifestations of threshold changes in nociceptive processing in the setting of injury do not appear to require SP or NKA [8].
  • These results indicate that the reduction of seizure activity and the neuroprotection observed in preprotachykinin A null mice are caused by the extinction of a SP/neurokinin A-mediated signaling pathway that is activated by seizures [9].
  • We found that GATA-1 strongly activates transcription of the Tac-2 gene, which encodes proneurokinin-B, a precursor of neurokinin-B (NK-B) [10].
  • Tac-2 was expressed in normal murine erythroid cells and was induced upon ex vivo erythropoiesis [10].

Biological context of Tac2


Anatomical context of Tac2


Associations of Tac2 with chemical compounds

  • The tachykinin NK(3) receptor-selective antagonist, SR 142801 (0.3 microM), had little effect on responses to SP and NKB [21].
  • The tachykinin NK(2) receptor may also participate in the responses to NKA and NKB [21].
  • SR48968 did not affect responses to SP or [Sar(9)Met(O(2))(11)]SP, but reduced the effect of higher concentrations of NKA and shifted the log concentration-response curve to NKB to the right [21].
  • Neurokinin A (0.1-3 micrograms) or senktide (0.0003-0.03 microgram) alone did not influence either spontaneous alternation performance or total arm entries [6].
  • The tachykinins neurokinin A and physalaemin stimulate murine thymocyte proliferation [22].

Regulatory relationships of Tac2

  • The activity of neuromedin K was blocked by the substance P antagonist [D-Pro2D-Trp7.9]substance P at doses of antagonist which effectively blocked the activity of the other tachykinins [23].

Other interactions of Tac2

  • Selective blockade of neurokinin-2 receptors produces antidepressant-like effects associated with reduced corticotropin-releasing factor function [24].
  • 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 [2].
  • SP proved to be the most efficient IL-2 inducer, exerting its maximal effect at concentrations that were 4 to 5 orders of magnitude lower than the optimal stimulatory concentrations of physalaemin, NKA, or NKB [25].
  • Accordingly, mice showed no NKB in the projection areas of these nuclei, such as the olfactory tubercle, whereas a clear NKB signal was present in rat tissues [17].
  • Characterization of the profile of neurokinin-2 and neurotensin receptor antagonists in the mouse defense test battery [26].

Analytical, diagnostic and therapeutic context of Tac2

  • NKA, and to a lesser extent PHY, but none of the other tachykinins tested, displayed a stimulatory action in murine thymocyte cultures, utilised as an interleukin-1 (IL-1) bioassay [22].
  • Because the antiserum K-12 recognizes various tachykinins, such as neurokinin A (100%), kassinin (103%), eledoisin (51%), neurokinin B (18%), physalaemin (0.7%), and substance P (0.7%), the immunoreactivity detected in this enzyme immunoassay has been termed TK-LI [27].
  • Two mouse monoclonal antibodies, 11H9.1 and 1G7.10, raised against the COOH-terminus peptide (359-390) of the rat neurokinin-2 receptor, were used to visualize by light and electron microscope immunocytochemistry the distribution of this receptor in adult rat spinal cord [28].
  • High-performance liquid chromatography (HPLC) fractions considered to represent neurokinin A, eledoisin and neuropeptide K were present in guinea-pig thymus but only the first two were present in rat thymus [29].
  • To assess vasoreactivity in small arteries, precision cut lung slices were subjected to videomorphometry and the response to NKA was examined, which showed significantly stronger effects in the BDNF-transgenic mice, while NK-2 receptor mRNA expression, assayed by real-time RT-PCR, was reduced [30].


  1. 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]
  2. 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]
  3. Inhibition of inflammatory cell recruitment by the tachykinin NK(3)-receptor antagonist, SR 142801, in a murine model of asthma. Nénan, S., Germain, N., Lagente, V., Emonds-Alt, X., Advenier, C., Boichot, E. Eur. J. Pharmacol. (2001) [Pubmed]
  4. Characterization of wide dynamic range neurons in the deep dorsal horn of the spinal cord in preprotachykinin-a null mice in vivo. Martin, W.J., Cao, Y., Basbaum, A.I. J. Neurophysiol. (2004) [Pubmed]
  5. Allergic airway inflammation induces tachykinin peptides expression in vagal sensory neurons innervating mouse airways. Dinh, Q.T., Mingomataj, E., Quarcoo, D., Groneberg, D.A., Witt, C., Klapp, B.F., Braun, A., Fischer, A. Clin. Exp. Allergy (2005) [Pubmed]
  6. Neurokinin A and senktide attenuate scopolamine-induced impairment of spontaneous alternation performance in mice. Ukai, M., Shinkai, N., Kameyama, T. Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology. (1996) [Pubmed]
  7. Primary afferent tachykinins are required to experience moderate to intense pain. Cao, Y.Q., Mantyh, P.W., Carlson, E.J., Gillespie, A.M., Epstein, C.J., Basbaum, A.I. Nature (1998) [Pubmed]
  8. Distinct neurochemical features of acute and persistent pain. Basbaum, A.I. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. Resistance to excitotoxin-induced seizures and neuronal death in mice lacking the preprotachykinin A gene. Liu, H., Cao, Y., Basbaum, A.I., Mazarati, A.M., Sankar, R., Wasterlain, C.G. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  10. Neurokinin-B transcription in erythroid cells: direct activation by the hematopoietic transcription factor GATA-1. Pal, S., Nemeth, M.J., Bodine, D., Miller, J.L., Svaren, J., Thein, S.L., Lowry, P.J., Bresnick, E.H. J. Biol. Chem. (2004) [Pubmed]
  11. Functional and molecular characterization of tachykinins and tachykinin receptors in the mouse uterus. Patak, E., Pinto, F.M., Story, M.E., Pintado, C.O., Fleming, A., Page, N.M., Pennefather, J.N., Candenas, M.L. Biol. Reprod. (2005) [Pubmed]
  12. Tachykinin-like immunoreactivity in the mammalian urinary bladder: correlation with the functions of the capsaicin-sensitive sensory nerves. Maggi, C.A., Geppetti, P., Santicioli, P., Frilli, S., Giuliani, S., Furio, M., Theodorsson, E., Fusco, B., Meli, A. Neuroscience (1988) [Pubmed]
  13. p38 mitogen-activated protein kinase expression and activation in smooth muscle. Hedges, J.C., Yamboliev, I.A., Ngo, M., Horowitz, B., Adam, L.P., Gerthoffer, W.T. Am. J. Physiol. (1998) [Pubmed]
  14. The role of the amino-terminal domain of tachykinins in neurokinin-1 receptor signaling and desensitization. Vigna, S.R. Neuropeptides (2003) [Pubmed]
  15. Long-term deprivation of substance P in PPT-A mutant mice alters the anoxic response of the isolated respiratory network. Telgkamp, P., Cao, Y.Q., Basbaum, A.I., Ramirez, J.M. J. Neurophysiol. (2002) [Pubmed]
  16. Modulation of memory retention by neuropeptide K. Flood, J.F., Baker, M.L., Hernandez, E.N., Morley, J.E. Brain Res. (1990) [Pubmed]
  17. Incongruent pattern of neurokinin B expression in rat and mouse brains. Duarte, C.R., Schütz, B., Zimmer, A. Cell Tissue Res. (2006) [Pubmed]
  18. Tachykinin production in granulomas of murine schistosomiasis mansoni. Weinstock, J.V., Blum, A.M. J. Immunol. (1989) [Pubmed]
  19. Phosphoramidon potentiates mammalian tachykinin-induced biting, licking and scratching behaviour in mice. Sakurada, T., Tan-No, K., Yamada, T., Sakurada, S., Kisara, K. Pharmacol. Biochem. Behav. (1990) [Pubmed]
  20. Characterization and autoradiographic localization of multiple tachykinin binding sites in gastrointestinal tract and bladder. Burcher, E., Buck, S.H., Lovenberg, W., O'Donohue, T.L. J. Pharmacol. Exp. Ther. (1986) [Pubmed]
  21. Functional characterization of tachykinin NK1 receptors in the mouse uterus. Patak, E., Pennefather, J.N., Fleming, A., Story, M.E. Br. J. Pharmacol. (2002) [Pubmed]
  22. The tachykinins neurokinin A and physalaemin stimulate murine thymocyte proliferation. Söder, O., Hellström, P.M. Int. Arch. Allergy Appl. Immunol. (1989) [Pubmed]
  23. Tachykinin-like central activity of neuromedin K in mice. Vaught, J.L., Post, L.J., Jacoby, H.I., Wright, D. Eur. J. Pharmacol. (1984) [Pubmed]
  24. Selective blockade of neurokinin-2 receptors produces antidepressant-like effects associated with reduced corticotropin-releasing factor function. Steinberg, R., Alonso, R., Griebel, G., Bert, L., Jung, M., Oury-Donat, F., Poncelet, M., Gueudet, C., Desvignes, C., Le Fur, G., Soubrié, P. J. Pharmacol. Exp. Ther. (2001) [Pubmed]
  25. Stimulation of IL-2 production in murine lymphocytes by substance P and related tachykinins. Rameshwar, P., Gascon, P., Ganea, D. J. Immunol. (1993) [Pubmed]
  26. Characterization of the profile of neurokinin-2 and neurotensin receptor antagonists in the mouse defense test battery. Griebel, G., Moindrot, N., Aliaga, C., Simiand, J., Soubrié, P. Neuroscience and biobehavioral reviews. (2001) [Pubmed]
  27. Enzyme immunoassay for tachykinin-like immunoreactivity in the guinea pig spinal cord. Renzi, D., Maillet, S., Grassi, J., Mantellini, P., Santicioli, P., Theodorsson, E., Surrenti, C., Geppetti, P. J. Neurochem. (1991) [Pubmed]
  28. Astroglial distribution of neurokinin-2 receptor immunoreactivity in the rat spinal cord. Zerari, F., Karpitskiy, V., Krause, J., Descarries, L., Couture, R. Neuroscience (1998) [Pubmed]
  29. Capsaicin-sensitive tachykinin-like immunoreactivity in the thymus of rats and guinea-pigs. Geppetti, P., Theodorsson-Norheim, E., Ballerini, G., Alessandri, M., Maggi, C.A., Santicioli, P., Amenta, F., Fanciullacci, M. J. Neuroimmunol. (1988) [Pubmed]
  30. BDNF-overexpression regulates the reactivity of small pulmonary arteries to neurokinin A. Springer, J., Wagner, S., Subramamiam, A., McGregor, G.P., Groneberg, D.A., Fischer, A. Regul. Pept. (2004) [Pubmed]
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