Tachykinin Receptors and their Antagonists

  • Carlo Alberto Maggi
  • Alessandro Lecci
Part of the NATO ASI Series book series (volume 79)


Tachykinins (TKs) are a family of peptides which share the common C-terminal sequence Phe-Xaa-Gly-Leu-MetNH2. Three peptides of this family, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) (Table I), have an established role as neurotransmitters in mammals. SP and NKA are produced through the expression of the same gene, preprotachykinin I (PPT I) while the PPT II gene encodes NKB.23,24 Two N-terminally extended forms of NKA, neuropeptide K and neuropeptide γ are also produced from the PPT I gene, but their status of neurotransmitters is not yet firmly established.


Dorsal Horn Neuron Conditioning Stimulation Tachykinin Receptor Nonpeptide Antagonist TACHYKININ Receptor Antagonist 
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  1. 1.
    Arai, H. and Emson, P.C. (1986) Regional distribution of neuropeptide K and other tachykinins (neurokinin A, neurokinin B and substance P) in rat central nervous system. Brain Res. 399, 240–249.PubMedCrossRefGoogle Scholar
  2. 2.
    Brunelleschi, S., Ceni, E., Fantozzi, R. and Maggi, C.A. (1992) Evidence for tachykinin NK-2B-like receptors in guinea-pig alveolar macrophages. Life Sci — Pharmacology Lett. 51, PL177–PL181.Google Scholar
  3. 3.
    Buck, S.H., Harbeson, S.L., Hassmann, III C.F., Shatzer, S.A., Rouissi, N., Nantel, F. and Van Giersbergen, P.L.M. (1990) [Leu9Y(CH2NH2)Leu10]-neurokinin A(4–10) (MDL 28,564) distinguishes tissue tachykinin peptide NK-2 receptors. Life Sci — Pharmacology Lett. 47, PL37–PL41.Google Scholar
  4. 4.
    Birch, P.J., Harrison, S.M., Hayes, A.G., Rogers, H. and Tyers, M.B. (1992) The nonpeptide NK-1 receptor antagonist, (±)CP 96,345, produces antinociceptive and antioedema effects in the rat. Br. J. Pharmacol. 105, 508–510.PubMedGoogle Scholar
  5. 5.
    Buck, S.H. and Shatzer, S.A. (1988) Agonist and antagonist binding to tachykinin peptide NK-2 receptor. Life Sci. 42, 2701–2708.PubMedCrossRefGoogle Scholar
  6. 6.
    Budai, D., Wilcox, G.L. and Larson, A.A. (1992) Modulation of NMDA and AMPA responses of spinal nociceptive neurons by a N-terminals fragment of Substance P. Eur. J. Pharmacol. 216, 441–444.PubMedCrossRefGoogle Scholar
  7. 7.
    Cascieri, M.A., Ber, E., Fong, T.M., Sadowski, S., Bansal, A., Swain, C., Seward, E., Frances, B., Burns, D. and Strader, C.D. (1992) characterization of the binding of a apotent, selective radioiodinated antagonist to the human neurokinin-1 receptor. Mol. Pharmacol. 42, 458–463.Google Scholar
  8. 8.
    De Koninck, Y. and Henry, J.L. (1991) Substance P-mediated slow excitatory postsynaptic potential elicited in dorsal horn neurons in vivo by noxious stimulation. Proc. Natl. Acad. Sci. USA 88, 11344–11348.PubMedCrossRefGoogle Scholar
  9. 9.
    Dougherty PM, Palececk J, Paleckova V, Sorkin LS, Willis WD (1993) The role of NMDA, non-NMDA and NK-1 receptors in the excitation of spinothalamic tract neurons in anaesthetized monkeys. J. Physiol. 459, 209 P.Google Scholar
  10. 10.
    Emonds Alt, X., Vilain, P., Goulaouic, P., Proietto, V., Van Broeck, D., Advenier, C., Naline, E., Neliat, G., L.E. Fur, G. and Breliere, J.C. (1992) A potent and selective nonpeptide antagonist of the neurokinin A (NK-2) receptor. Life Sci. — Pharmacology Lett. 50, PL101–106.Google Scholar
  11. 11.
    Fong, T.M., Yu, H. and Strader, C.D. (1992) Molecular basis for the species selectivity of the NK-1 receptor antagonists CP 96,345 and RP 67,580. J. Biol. Chemistry 267, 25668–25671.Google Scholar
  12. 12.
    Freedman. J., Post, C., Kahrstrom, J., Hokfelt, T., Ohlen, A., Mollenholt, P., Owman, C., Alar I, L. and Hokfelt, T. (1988) Vasoconstrictor effects in spinal cord of the substance P antagonist [D- Arg1, D-Trp7,9, Leu11]-substance P (spantide) and somatostatin and interaction with thyrotropin releasing hormone. Neuroscience 27, 267–278.PubMedCrossRefGoogle Scholar
  13. 13.
    Garret, C., Carruette, A., Fardin, V., Moussaoui, S., Peyronel, J.F., Blanchard, J.C. and Laduron, P.M. (1991) Pharmacological properties of a potent and selective nonpeptide substance P antagonist. Proc. Natl. Acad. Sci. USA 88, 10208–10211.PubMedCrossRefGoogle Scholar
  14. 14.
    Gerard, N.P., Bao, L., Xiao-Ping, H. and Gerard, C. (1993) Molecular aspects of the tachykinin receptors, Regul. Peptides 43, 21–35.CrossRefGoogle Scholar
  15. 15.
    Gitter, B.D., Waters, D.C., Bruns, R.F., Mason, N.R., Nixon, J.A. and Howbert, J.J. (1991) Species differences in affinities of nonpeptide antagonists for substance P receptors. Eur. J. Pharmacol. 197, 237–238.PubMedCrossRefGoogle Scholar
  16. 16.
    Guard, S. and Watson, S.P. (1991) Tachykinin receptor types: classification and mebrane signalling mechanisms. Neurochem. Int. 18, 149–165.PubMedCrossRefGoogle Scholar
  17. 17.
    Helke, C.J., Krause, J.E., Mantyh, P.W., Couture, R. and Bannon, M.J. (1990) Diversity in mammalian tachykinin peptidergic neurons: multiple peptides, receptors and regulatory mechanisms. FASEB J. 4, 1606–1615.PubMedGoogle Scholar
  18. 18.
    Hill, J.M., Pickar, J.G. and Kaufman, M.P. (1992) Attenuation of reflex pressor and ventilatory responses to static contraction by an NK-1 receptor antagonist. J. Appl. Physiol. 73, 1389–1395.PubMedGoogle Scholar
  19. 19.
    Hokfelt, T., Kellerth, J.O., Nilsson, G. and Pernow, B. (1975) Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Res. 100, 235–252.PubMedCrossRefGoogle Scholar
  20. 20.
    Igwe, O.J., Sun, X. and Larson, A.A. (1990) Specific binding of substance P aminoterminal heptapeptide SP(1–7) to mouse brain and spinal cord membranes. J. Neurosci. 10, 3653–3663.PubMedGoogle Scholar
  21. 21.
    Kage, R., Leeman, S.E. and Boyd, N.D. (1993) Biochemical characterization of two different forms of the substance P receptor in rat submaxillary glands, J. Neurochemistry 60, 347–351.CrossRefGoogle Scholar
  22. 22.
    Kanazawa, I., Ogawa, T., Kimura, S. and Munekata, E. (1984) Regional distribution of substance P, neurokinin A and neurokinin B in rat central nervous system. Neurosci. Res. 2, 111–120.PubMedCrossRefGoogle Scholar
  23. 23.
    Kotani, H., Hoshimaru, M., Nawa, H., and Nakanishi, S. (1986) Structure and gene organization of bovine neuromedin K precursor. Proc. Natl. Acad. Sci. USA 83, 7074–7078.PubMedCrossRefGoogle Scholar
  24. 24.
    Krause, J.E., Chirgwin, J.M., Carter, M.S., Xu, Z.S. and Hershey, A.D. (1987) Three rat preprotachykinin mRNAs encode the neuropeptides substance P and neurokinin A. Proc. Natl. Acad. Sci. USA 84, 881–885.PubMedCrossRefGoogle Scholar
  25. 25.
    Larson, A.A. and Sun, X. (1992) Aminoterminus of substance P potentiates kainic acid-induced activity in the mouse spinal cord. J. Neurosci. 12, 4905–4910.PubMedGoogle Scholar
  26. 26.
    Leander, S., Hakanson, R., Rosell, S., Folkers, K., Sundler, F. and Tornqvist, K. (1981) A specific substance P antagonist blocks smooth muscle contractions induced by noncholinergic nonadrenergic nerve stimulation. Nature 294, 467–469.PubMedCrossRefGoogle Scholar
  27. 27.
    Lecci, A., Giuliani, S., Patacchini, R., Viti, G. and Maggi, C.A. (1991) Role of NK-1 tachykinin receptors in thermonociception: effect of (±)CP 96,345, a nonpeptide substance P antagonist on the hot plate test in mice. Neurosci. Lett. 129, 299–302.PubMedCrossRefGoogle Scholar
  28. 28.
    Lecci, A., Giuliani, S. and Maggi, C.A. (1992) Effect of the NK-1 receptor antagonist GR 82,334 on reflexly-induced bladder contractions. Life Sci. — Pharmacology Lett. 51, PL277–PL280.Google Scholar
  29. 29.
    Lecci, A, Giuliani S., Garret, C. and Maggi, C.A. (1993) Evidence for a role of tachykinins as sensory transmitters in the activation of micturition reflex. Neuroscience (in press).Google Scholar
  30. 30.
    Lee, C.M., Iversen, L.L., Hanley, M.R. and Sandberg, B.E.B. (1982) The possible existence of multiple receptors for substance P. Naunyn Schmied Arch. Pharmacol. 318, 281–288.CrossRefGoogle Scholar
  31. 31.
    Lembeck, F. (1953) Zur Frage der zentralen Ubertragung afferenter Impulse III Mitteilung. Das Vorkommen und die Bedeutung der Substanz P in den dorsalen Wurzeln des Ruckenmarks. Arch. Exp. Path. Pharmakol. 219, 197–213.CrossRefGoogle Scholar
  32. 32.
    Maggi, C.A., Patacchini, R., Giuliani, S., Rovero, P., Dion, S., Regoli, D., Giachetti, A. and Meli, A. (1990) Competitive antagonists discriminate between NK-2 tachykinin receptor subtypes. Br. J. Pharmacol. 100, 588–592.Google Scholar
  33. 33.
    Maggi, C.A., Patacchini, R., Meini, S. and Giuliani, S (1993) Evidence for the presence of a septide-sensitive tachykinin receptor in the circular muscle of the guinea-pig ileum. Eur. J. Pharmacol, (in press).Google Scholar
  34. 34.
    Maggi, C.A., Patacchini, R., Rovero, P., and Giachetti, A. (1993) Tachykinin receptors and receptor antagonists. J. Autonom. Pharmacol. 13, 1–70.CrossRefGoogle Scholar
  35. 35.
    Meini, S., Patacchini, R. and Maggi, C.A. (1993) Tachykinin NK-1 receptor subtypes in the rat urinary bladder Br. J. Pharmacol, (in press).Google Scholar
  36. 36.
    Nagahisa, A., Asai, R., Kana, I Y., Murase, A., Tsuchiya-Nakagaki, M., Nakagaki, T., Shieh, T.C. and Taniguchi, K. (1992b) Nonspecific activity of (±)CP 96,345 in models of pain and inflammation. Br. J. Pharmacol. 107, 273–275.PubMedGoogle Scholar
  37. 37.
    Nagahisa, A., Kanai, Y., Suga, O., Taniguchi, K., Tsuchiya, M., Lowe, III J.A. and Hess, H.J. (1992a) Antinflammatory and analgesic activity of a nonpeptide substance P receptor antagonist. Eur. J. Pharmacol. 217, 191–195.PubMedCrossRefGoogle Scholar
  38. 38.
    Nagy, I., Maggi, C.A., Dray, A., Woolf, C.J. and Urban, L. (1993) The role of neurokinin and NMDA receptors in synaptic transmission from capsaicin-sensitive primary afferents in the rat spinal cord in vitro. Neuroscience 52, 1029–1037.PubMedCrossRefGoogle Scholar
  39. 39.
    Nakanishi, S. (1991) Mammalian tachykinin receptors. Annu. Rev. Neuroscience 14, 123–136CrossRefGoogle Scholar
  40. 40.
    Nimmo, A., Carstairs, J.R., Maggi, C.A. and Morrison, J.F.B. (1992) Evidence for the co-existence of multiple NK-2 tachykinin receptor subtypes in rat bladder. Neuropeptides 22, 48.CrossRefGoogle Scholar
  41. 41.
    Otsuka, M. and Yanagisawa, M. (1988) Effect of a tachykinin antagonist on a nociceptive reflex in the isolated spinal cord-tail preparation of the newborn rat. J. Physiol. 395, 255–270.PubMedGoogle Scholar
  42. 42.
    Patacchini, R., Astolfi, M., Quartara, L., Rovero, P., Giachetti, A., and Maggi, C.A. (1991) Further evidence for the existence of NK-2 tachykinin receptor subtypes. Br. J. Pharmacol. 104, 91–96.PubMedGoogle Scholar
  43. 43.
    Patacchini, R., Santicioli, P., Astolfi, M., Rovero, P., Viti, G. and Maggi, C.A. (1992) Activity of peptide and non-peptide antagonists at peripheral NK-1 tachykinin receptors. Eur. J. Pharmacol. 215, 93–98.PubMedCrossRefGoogle Scholar
  44. 44.
    Petitet, F., Saffroy, M., Torrens, Y., Lavielle, S., Chassaing, G. Loeuillet, D., Glowinski, J. and Beaujoan, J.C. (1992) Possible existence of a new tachykinin receptor subtype in the guinea-pig ileum. Peptides 13, 383–388.PubMedCrossRefGoogle Scholar
  45. 45.
    Radhakrishnan, V., and Henry, J.L. (1991) Novel substance P antagonist, CP 96,345 blocks responses of cat spinal dorsal horn neurons to noxious cutaneous stimulation and to substance P. Neurosci Lett. 132, 39–43.PubMedCrossRefGoogle Scholar
  46. 46.
    Regoli, D., Drapeau, G., Dion, S. and D’Orleans-Juste, P. (1986) in Substance P and neurokinins, Montreal ‘86, eds. J.L. Henry et al. Springer-Verlag, New York.Google Scholar
  47. 47.
    Snider, R.M., Constantine, J.W., Lowe, III J.A., Longo, K.P., Lebel, W.S., Woody, H.A., Drozda, S.E., Desai, M.C., Vinick, F.J., Spencer, R.W. and Hess, H.J. (1991) A potent nonpeptide antagonist of the substance P (NK-1) receptor. Science 251, 435–437.PubMedCrossRefGoogle Scholar
  48. 48.
    Stewart, J.M., Hall, M.E., Harkins, J., Frederickson, R.C.A., Terenius, L., Hokfelt, T. and Krivoy, W.A. (1982) A fragment of substance P with speicific central activity: SP(1–7). Peptides 3, 851–857.PubMedCrossRefGoogle Scholar
  49. 49.
    Thompson, S.W.N., Dray, A. and Urban, L. (1993) The contribution of tachykinin receptor activation to C-fibre-evoked responses in the neonatal rat spinal cord in vitro. J. Physiol. 459, 464 P.Google Scholar
  50. 50.
    Van Giersbergen, P.L.M, Shatzer, S.A., Henderson, A.K., Lai J., Nakanishi, S., Yamamura, H.I. and Buck, S.H. (1991) Characterization of a tachykinin peptide NK-2 receptor transfected into murine fibroblast B82 cell. Proc. Natl. Acad.Sci. USA 88, 1661–1665.PubMedCrossRefGoogle Scholar
  51. 51.
    Yamamoto, T. and Yaksh, T.L. (1991) Stereospecific effects of a nonpeptidic NK-1 selective antagonist CP 96,345: antinociception in the absence of motor dysfunction. Life Sci. 49, 1955–1963.PubMedCrossRefGoogle Scholar
  52. 52.
    Xu, X.J., Dalsgaard, C.J. and Wiesenfeld-Hallin, Z. (1992) Intrathecal CP 96,345 blocks reflex facilitation induced in rats by substance P and C-fiber conditioning stimulation. Eur.J. Pharmacol. 216, 337–344.PubMedCrossRefGoogle Scholar
  53. 53.
    Xu X.J., Maggi, C.A and Wiesenfeld-Hallin, Z. (1991) On the role of NK-2 tachykinin receptors in the mediation of spinal reflex excitability in the rat. Neuroscience 44, 483–490.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • Carlo Alberto Maggi
    • 1
  • Alessandro Lecci
    • 1
  1. 1.Department of PharmacologyA. Menarini PharmaceuticalsFlorenceItaly

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