Molecular Biology of Receptors

Structures, Expression, and Regulatory Mechanisms
  • James E. Krause
  • Paul Blount
  • Bruce S. Sachais
Part of the The Receptors book series (REC)


The tachykinin peptides comprise a family of structurally related peptides that were originally discovered on the basis of their atropine resistant, rapid stimulation of smooth muscle contraction. These peptides have been isolated from vertebrate and invertebrate species and are structurally characterized by the conserved carboxyl-terminal region of Phe-X-Gly-Leu-MetNH2where the X residue usually is an aromatic or aliphatic amino acid. There exist at least five mammalian tachykinin peptides including substance P (SP), neurokinin A (NKA), neurokinin B (NKB), neuropeptide K (NPK), and neuropeptide y (NPy) that are synthesized, processed, and secreted from tachykinin secreting neurons, as well as certain nonneural tissues and cells. NPK and NPy are amino terminal extended forms of NKA. Each of the five peptides is an agonist at each of the currently characterized tachykinin receptors, although their rank orders of potency differ. Mammalian tachykinin receptors consist of three types based upon current pharmacological, biochemical, and molecular characterization. These receptors have been named neurokinin-1 (NK1), the receptor with highest affinity for SP; neurokinin-2 (NK2), the receptor with highest affinity for NKA, NPK, and NPy; and neurokinin-3 (NK3), the receptor with highest affinity for NKB.


Agonist Binding Chimeric Receptor Tachykinin Receptor Antagonist Binding Substance Preceptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Appell, K. C., Fragale, B. J., Loscig, J., Singh, S., and Tomczuk, B. E. (1992) Antagonists that demonstrate species differences in neurokinin-1 receptors.J. Pharm. Exp. Ther. 41, 772–778.Google Scholar
  2. Bernstein, G., Blank, J. L., Jhon, D.-Y., Exton, J. H., Rhee, S. G., and Ross, E. M. (1992) Phosphlipase C-ß1 is a GTPase-activating protein for Ga11its physiological regulator.Cell 70, 411–418.CrossRefGoogle Scholar
  3. Berridge, M. J. (1993) Insoitol trisphosphate and calcium signaling.Nature 361, 315–325.PubMedCrossRefGoogle Scholar
  4. Blount, P. and Krause, J. E. (1993) Functional nonequivalence of structurally homologous domains of neurokinin-1 and neurokinin-2 type tachykinin receptors.J. Biol. Chem. 268, 16,388–16,395.PubMedGoogle Scholar
  5. Boyd, N. D., White, C. F., Cerpa, R., Kaiser, E. T., and Leeman, S. E. (1991) Photoaffinity labeling the substance P receptor using a derivative of substance P containing p-benzoylphenylalanine.Biochemistry 30, 336–342.PubMedCrossRefGoogle Scholar
  6. Brunner, J. (1993) New photolabelling and crosslinking methods.Ann. Rev. Biochem. 62, 483–514.PubMedCrossRefGoogle Scholar
  7. Buck, S. H. and Shatzer, S. A. (1988) Agonist and antagonist binding to tachykinin peptide NK-2 receptors.Life Sci. 42, 2701–2708.PubMedCrossRefGoogle Scholar
  8. Buck, S. H., Helke, C. J., Burcher, E., Shults, C. W., and O’Donohue, T. L. (1986) Pharmacologic characterization and autoradiographic distribution of binding sites for iodinated tachykinins in the rat central nervous system.Peptides 7, 1109–1120.PubMedCrossRefGoogle Scholar
  9. Buck, S. H., Burcher, E., Shults, C. W., Lovenberg, W., and O’Donohue, T. L. (1984) Novel pharmacology of substance K-binding sites: a third type of tachykinin receptor.Science 266, 987–989.CrossRefGoogle Scholar
  10. Buell, G., Schulz, M. F., Arkinstall, S. J., Maury, K., Missotten, M., Adami, N., Talabot, F., and Kawashima, E. (1992) Molecular characterisation, expression and localisation of human neurokinin-3 receptor.FEBS 299, 90–95.CrossRefGoogle Scholar
  11. Cascieri, M.A., Chicchi, G. G., and Liang, T. (1985) Demonstration of two distinct tachykinin receptors in rat brain cortex.J. Biol. Chem. 260, 1501–1507.PubMedGoogle Scholar
  12. Cascieri, M. A. and Liang, T. (1983) Characterization of the substance P receptor in rat brain cortex membranes and the inhibition of radioligand binding by guanine nucliotides.J. Biol. Chem. 258, 5158–5164.PubMedGoogle Scholar
  13. Couture, R., Fournier, A., Magnan, J., St-Pierre, S., and Regoli, D. (1979) Structureactivity studies on substance P.Can. J. Pysiol. 57, 1427–1436.CrossRefGoogle Scholar
  14. Dam, T.-V., Takeda, Y., KrauseJ.E., Escher, E., and Quirion, R. (1990) yPreprotachykinin-(72–92)-peptide amide: An endogenous preprotachykinin I gene-derived peptide that preferentially binds to neurokinin-2 receptors. Proc. Natl. Acad. Sci. USA 87, 246–250.PubMedCrossRefGoogle Scholar
  15. DeBernardi, M. A., Seki, T., and Brooker, G. (1991) Inhibition of cAMP accumulation by intracellular calcium mobilization in C6–2B cells stably transfected with substance K receptor cDNA.Proc. Natl. Acad. Sci. USA 88, 9257–9261.PubMedCrossRefGoogle Scholar
  16. Dietl, M. M. and Palacios, J. M. (1991) Phylogeny of tachykinin receptor localization in the vertebrate central nervous system: Apparent absence of neurokinin-2 and neurokinin-3 binding sites in the human brain.Brain Res. 539, 211–222.PubMedCrossRefGoogle Scholar
  17. Dion, S., Nantel, R. F., Jukic, D., Rhaleb, N. E., Tousignant, S., Telemasque, S., Drapeau, G., Regoli, D., Naline, C., Advenier, C., Rovero, P., and Maggi, C. A. (1990) Structure-activity study of neurokinins: Antagonists for the neurokinin-2Receptor. Pharm. 41, 184–194.CrossRefGoogle Scholar
  18. Dubuisson, D. and Dennis, S. G. (1977) The formalin test: A quantitative study of the analgenic effects of morphine, meperidine, and brain stem stimulation in rats and cats.Pain 4, 161–174.PubMedCrossRefGoogle Scholar
  19. Eistetter, H. R., Church, D. J., Mills, A., et al (1991) Recombinant bovine neurokinin2 receptor stably expressed in Chinese hamster ovary cells couples to multiple signal transduction pathways.Cell Reg. 2, 767–779.Google Scholar
  20. Emonds-Alt, X., Vilain, P., Goulaouic, P., Proietto, D., Van Broeck, D., Advenier, C., Naline, E., Neliat, G., LeFur, G., and Breliere, J. C. (1992) A potent and selective nonpeptide antagonist of the neurokinin A (NK-2) receptor.Life Sci. 50, 101–106.CrossRefGoogle Scholar
  21. Folkers, K., Hakanson, R., Horig, J., Jie-Cheng, X., and Leander, S. (1984) Biological evaluation of substance P antagonists.Br. J. Pharmacol. 83, 449–456.PubMedCrossRefGoogle Scholar
  22. Fong, T. M., Anderson, S. A., Yu, H., Huang, R.-R. C., and Strader, C. D. (1992a) Differential activation of intracellular effector by two isoforms of human neurokinin-1 receptor.Mol. Pharmacol. 41, 24–30.Google Scholar
  23. Fong, T. M., Huang, R. C., and Strader, C. D. (1992b) Localization of agonist and antagonist binding domains of the human neurokinin-1 receptor. J.Biol. Chem. 267, 25,664–25,667.Google Scholar
  24. Fong, T. M., Yu, H., Huang, R. C., and Strader, C. D. (1992c) The extracellular domain of the neurokinin-1 receptor is required for high affinity binding of peptides.Biochemistry 31, 11,806–11,811.CrossRefGoogle Scholar
  25. Fong, T. M., Yu, H., and Strader, C. D. (1992d) Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580.J. Biol. Chem. 267, 25,668–25,671.Google Scholar
  26. Fong, T. M., Cascieri, M. A., Yu, H., Bansal, A., Swain, C., and Strader, C. D. (1993) Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345.Nature 362, 350–353.PubMedCrossRefGoogle Scholar
  27. Franke, R. R., König, B., Sakmar, T. P., Khorana, H. G., and Hofman, K. P. (1990) Rhodopsin mutants that bind but fail to activate transducin.Science 250,123–125.PubMedCrossRefGoogle Scholar
  28. Garret, C., Carruette, A., Fardin, V., Moussaoui, S., Peyronei, J., Blanchard, L., and Laduron, P. M. (1991) Pharmacological properties of a potent and selective nonpeptide substance P antagonist.Proc. Natl. Acad. Sci. USA 88,10,208–10,212.PubMedCrossRefGoogle Scholar
  29. Gerard, N. P., Bao, L., Xiao-Ping, H., and Gerard, C. (1993) Molecular aspects of the tachykinin receptors.Regul. Pept. 43, 21–35.PubMedCrossRefGoogle Scholar
  30. Gerard, N. P., Garraway, L. A., Eddy, R. L., Shows, T. B., Iijima, H., Paquet, J., and Gerard, C. (1991) Human substance P receptor (NK-1): Organization of the gene, chromosome localization, and functional expression of cDNA clones.Biochemistry 30, 10,640–10,646.PubMedCrossRefGoogle Scholar
  31. Gerard, N. P., Eddy, R. L., Jr., Shows, T. B., and Gerard, C. (1990) The human neurokinin A (substance K) receptor.J. Biol. Chem. 265 20,455–20,462.PubMedGoogle Scholar
  32. Gether, U., Johansen, T. E., Snider, R. M., Lowe III, J. A., Nakanishi, S., and Schwartz, T. W. (1993a) Different binding epitopes on the NK-1 receptor for substance P and a nonpeptide antagonist.Nature 362, 345–348.CrossRefGoogle Scholar
  33. Gether, U., Yokota, Y., Edmonds-Alt, X., Berliere, J.-C., Lowe, J. A., Snider, R. M., Nakanishi, S., and Schwartz, T. W. (1993b) Two nonpeptide tachykinin antagonists act through epitopes on corresponding segments of the NK-1 and NK-2 receptors.Proc. Natl. Acad. Sci. USA 90, 6194–6198.CrossRefGoogle Scholar
  34. Gether, U., Johansen, T. E., and Schwartz, T. W. (1993) Chimeric NK1(substance P)/ NK3(neurokinin B) receptors: identification of domains determining the binding specificity of tachykinin agonists.J. Biol. Chem. 268, 7893–7898.PubMedGoogle Scholar
  35. Gorbulev, V., Akhundova, A., Luzius, H., and Fahrenholz, F. (1992) Molecular cloning of substance P receptor cDNA from guinea pig uterus.Biochem. Biophys. Acta 1131, 99–102.PubMedCrossRefGoogle Scholar
  36. Graham, A., Hopkins, B., Powell, S. J., Danks, P. and Briggs, I. (1991) Isolation and characterization of the human lung NK-1 receptor gene using rapid amplification of cDNA ends.Biochem. Biophys. Res. Comm. 177, 8–16.PubMedCrossRefGoogle Scholar
  37. Guard, S. and Watson, S. P. (1991) Tachykinin receptor types: classification and membrane signaling mechanisms.Neurochem. Int. 18, 149–169.PubMedCrossRefGoogle Scholar
  38. Hanley, M. R., Lee, C.-M., Jones, L. M., and Michell, R. H. (1980) Similar effects of substance P and related peptides on salivation and phosphatidylinositol turnover in rat salivary glands.Mol. Pharmacol. 18, 78–83.PubMedGoogle Scholar
  39. Harada, Y., Takahashi, T., Kuno, M., Nakayama, K., Masu, Y., and Nakanishi, S. (1987) Expression of two different tachykinin receptors in Xenopus oocytes by exogenous mRNAs.J. Neurosci. 7, 3265–3273.PubMedGoogle Scholar
  40. Helke, C. J., Krause, J. E., Mantyh, P. W., Couture, R., and Bannon, M. J. (1990) Diversity in mammalian tachykinin peptidergic neruons: multiple peptides, receptors, and regulatory mechanisms.FASEB J. 4, 1606–1615.PubMedGoogle Scholar
  41. Hershey, A. D., Dykema, P. E., and Krause, J. E. (1991) Organization, structure, and expression of the gene encoding the rat substance P receptor.J. Biol. Chem. 266, 4366–4374.PubMedGoogle Scholar
  42. Hershey, A. D. and Krause, J. E. (1990) Molecular characterization of a functional cDNA encoding the rat substance P receptor.Science 247, 958–961.PubMedCrossRefGoogle Scholar
  43. Hopkins, B., Powell, S. J., Dankal, P., Briggs, I., and Graham, A. (1991) Isolation and characterization of the human lung NK-1 receptor cDNA.Biochem. Biophys. Res. Commun. 180, 1110–1117.PubMedCrossRefGoogle Scholar
  44. Huang, R.-R. C., Cheung, A. H., Mazina, K. E., Strader, C. D., and Fong, T. M. (1992) cDNA sequence and heterologous expression of the human neurokinin-3 receptor.Biochem. Biophys. Res. Commun. 184, 966–972.PubMedCrossRefGoogle Scholar
  45. Hunter, J. C., Goedert, M., and Pinnock, R. D. (1985) Mammalian tachykinin-induced hydrolysis of inositol phospholipids in rat brain slices.Biochem. Biophys. Res. Commun. 127, 616–622.PubMedCrossRefGoogle Scholar
  46. Iadarola, M. J., Brady, L. S., Draisci, G., and Dubner, R. (1988a) Enhancement of dynorphin gene expression in spinal cord following experimental inflammation: Stimulus specificity, behavioral parameters and opioid receptor binding.Pain 35, 313–326.CrossRefGoogle Scholar
  47. Iadarola, M. J., Douglass, J., Civelli, O., and Naramjo, J. R. (1988b) Different activation of spinal cord dymorphin and enkephalin neurons during hyperalgesia: Evidence using cDNA hybridization.Pain Res. 455, 205–212.Google Scholar
  48. Ihara, H. and Nakanishi, S. (1990) Selective inhibition of expression of the substance P receptor mRNA in pancreatic acinar AR42J cells by glucocorticoids. J. Biol. Chem.265 22,441–22,445.PubMedGoogle Scholar
  49. Ingi, T., Kitaima, Y., Minamitake, Y., and Nakanishi, S. (1991) Characterization of ligand-binding properties and selectivities of three rat tachykinin receptors by transfection and functional expression of their cloned cDNAs in mammalian cells.J. Pharmacol. Exper. Ther. 259, 968–975.Google Scholar
  50. Joslin, G., Krause, J. E., Hershey, A. D., Adams, S. P., Fallon, R. J., and Perlmutter, D. H. (1991) Amyloid-peptide, substance P, and bombesin bind to the serpinenzyme complex receptor. J. Biol. Chem. 266 21,897–21,902.PubMedGoogle Scholar
  51. Krause, J. E., Takeda, J., Cremins, J. D., and Raddatz, R. (1991) Regulation of substance P receptor mRNA expression by cAMP and glucocorticoids in human and rat cell lines.Soc. Neurosci. Abstr. 17, 188.Google Scholar
  52. Krause, J. E., Sachais, B. S., and Blount, P. (1993a) Tachykinin receptors, inHandbook of Receptors and Channelsvol. 1: G protein coupled receptors (Peroutka, S. J., ed.), CRC, FL, pp. 277–298.Google Scholar
  53. Krause, J. E., Bu, J.-Y., Takeda, Y., Blount, P., Raddatz, R., Sachais, B. S., Chou, K. B., Takeda, J., McCarson, K. E., and DiMaggio, D. (1993b) Structure, expression and second-messenger mediated regulation of the human and rat substance P receptors and their genes.Regul. Pept. 46, 59–66.CrossRefGoogle Scholar
  54. Kris, R. M., South, V., Saltzman, A., Felder, S., Ricca, G. A., Jaye, M., Huebner, K., Kagan, J., Croce, C. M., and Schlessinger, J. (1991) Cloning and expression of the human substance K receptor and analysis of its role in mitogenesis.Cell Growth Differen. 2, 15–22.Google Scholar
  55. Kwatra, M. M., Schwinn, D. A., Schreurs, J., Blank, J. L., Kim, C. M., Benovic, J. L., Krause, J. E., Caron, M. G., and Lefkowitz, R. J. (1993) The substance P receptor which couples to Goois a substrate of (3-adrenergic receptor kinase 1 and 2.J. Biol. Chem. 268, 9161–9164.PubMedGoogle Scholar
  56. Laufer, R., Gilon, C., Chorev, M., and Selinger, Z. (1988) Desensitization with a selective agonist discriminates between multiple tachykinin receptors.J. Pharmacol. Exper. Ther. 245, 639–643.Google Scholar
  57. Laufer, R., Gilon, C., Chorev, M., and Selinger, Z. (1986) Characterization of a neurokinin B receptor site in rat brain using a highly selective radioligand. J. Biol. Chem.261, 10,257–10,263.PubMedGoogle Scholar
  58. Laufer, R., Wormser, U., Friedman, Z. Y., Gilon, C., Chorev, M., and Selinger, Z. (1985) Neurokinin B is a preferred agonist for a neuronal substance P receptor and its action is antagonized by enkephalin.Proc. Natl. Acad. Sci. USA 82, 7444–7448.PubMedCrossRefGoogle Scholar
  59. Lavielle, S., Chassaing, G., Ploux, 0., Louillet, D., Besseyre, J., Julien, S., Marquet, A., Convert, O., Beauouan, J.-C., Torrens, Y., Bergstrom, L., Saffroy, M., and Glowinski, J. (1988) Analysis of tachykinin binding site interactions using constrained analogues of tachykinins.Biochem. Pharmacol. 37, 41–49.PubMedCrossRefGoogle Scholar
  60. 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 Schmiedeberg’s Arch. Pharmacol. 318, 281–287.CrossRefGoogle Scholar
  61. Lee, C.-M., Javitch, J. A., and Snyder, S. H. (1983)3H-Substance P binding to salvary gland membranes: regulation by guanyl nucleotides and divalent cations.Mol. Pharmacol. 23, 563–569.PubMedGoogle Scholar
  62. Levian-Teitelbaum, D., Kolodny, N., Chorev, M., Selinger, Z., and Gilon, C. (1989)3H-NMR Studies of receptor-selective substance P analogs reveal distinct predominant conformations in DMSO-d6 Biopolymers 28, 51–64.PubMedCrossRefGoogle Scholar
  63. Li, X. J., Wolfgang, W., Wu, Y.-N., North, R. A., and Forte, M. (1991) Cloning, heterlogous expression and developmental regulation of aDrosophilareceptor for tachykinin-like peptides.EMBO J. 10, 3221–3229.PubMedGoogle Scholar
  64. Luber-Narod, J., Boyd, N. D., and Leeman, S. E. (1990) Guanine nucleotides decrease the affinity of substance P binding to its receptor.Euro. J. Pharmacol. 188, 185–191.CrossRefGoogle Scholar
  65. MacDonald, S. G. and Boyd, N. D. (1989) Regulation of substance P receptor affinity by guanine nucliotide-binding proteins.J. Neurochem. 53, 264–272.PubMedCrossRefGoogle Scholar
  66. Maggi, C. A., Eglezos, A., Quartara, R., Patacchini, R., and Giachetti, A. (1992) Heterogeneity of NK-2tachykinin receptors in hamster and rabbit smooth muscles.Regul. Pept. 37, 85–93.PubMedCrossRefGoogle Scholar
  67. Maggi, C. A., Patacchini, R., Giuliani, S., Rovero, P., Dion, S., Regoli, D., Giachetti, A., and Meli, A. (1990) Competitive antagonists discriminate between NK2tachykinin receptor subtypes.Br. J. Pharmacol. 100, 588–592.CrossRefGoogle Scholar
  68. Mantyh, P. W., Pinnock, R. D., Downes, C. P., Goedert, M., and Hunt, S. P. (1984) Coorelation between inositol phospholipid hydrolysis and substance P receptors in rat CNS.Nature 309, 795–797.PubMedCrossRefGoogle Scholar
  69. Masu, Y., Nakayama, K., Tamaki, H., Harada, Y., Kuno, M., and Nakanishi, S. (1987) cDNA cloning of bovine substance-K receptor through oocyte expression system.Nature 329, 836–838.PubMedCrossRefGoogle Scholar
  70. McCarson, K. E. and Krause, J. E. (1994) NK-1 and NK-3 type tachykinin receptor mRNA expression in the rat spinal cord dorsal horm is increased during aduvant or formalin-induced nociception.J. press.Google Scholar
  71. McKnight, A. T., Maguire, J. J., Elliott, N. J., Fletcher, A. E., Foster, A. C., Tridgett, R., Williams, B. J., Longmore, J., and Iverson, L. L. (1991) Phamacological specificity of novel, synthetic, cyclic peptides as antagonists at tachykinin receptors.Br. J. Pharm. 104, 355–360.CrossRefGoogle Scholar
  72. Merritt, J. E. and Rink, T. J. (1987) The effects of substance P and carbachol on inositol tris-and tetrakisphosphate formation and cytosolic free calcium in rat parotid acinar cells.J. Biol. Chem. 262 14,912–14,916.PubMedGoogle Scholar
  73. Mitsuhashi, M., Ohashi, Y., Scichio, S., Christian, C., Sudduth-Klinger, J., Harrowe, G., and Payan, D.G. (1992) Multiple intracellular signaling pathways of the neuropeptide substance P receptor.J. Neurosci. Res. 32, 437–443.PubMedCrossRefGoogle Scholar
  74. Monnier, D., Colas, J.-F., Rosay, P., Hen, R., Borrelli, E., and Maroteaux, L. (1992) NKD, a developmentally regulated tachykinin receptor in Drosophila.J. Biol. Chem. 267, 1298–1302.PubMedGoogle Scholar
  75. Morimoto, H., Murai, M., Maeda, Y., Yamaoka, M., Nishikana, M., Kiyotoh, S., and Fuii, T. (1992) FR 224, a novel cyclopeptide substance P antagonist with NK-1 and NK-2 selectivity.J. Pharmacol. Exp. Ther. 262, 398–402.PubMedGoogle Scholar
  76. Mousli, M., Baeb, J.-L., Bronner, C., Rauot, B., and Landry, Y. (1990) G-protein activation: A receptor-independent mode of action for Ca’ ionic amphiphilic neuropeptides and venom peptides.Trends Pharmacol. Sci. 11, 358–362.PubMedCrossRefGoogle Scholar
  77. Murai, M., Morimoto, H., Maeda, Y., Kiyotoh, S., Nishikawa, M., and Fujii, T. (1992) Effects of FK 224, a novel compound NK-1 and NK-2 receptor antagonist, on airway constriction and airway edema induced by neurokinins and sensory nerve stimulation in guinea pigs.J. Pharmacol. Exp. Ther. 262, 403–408.PubMedGoogle Scholar
  78. Nakaima, Y., Tsuchida, K., Negishi, M., Ito, S., and Nakanishi, S. (1992) Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cyclic AMP cascades in transfected Chinese hamster ovary cells.J. Biol. Chem. 267, 2437–2442.Google Scholar
  79. Nakanishi, S. (1991) Mammalian tachykinin receptors.Annu. Rev. Neurosci. 14, 123–136.PubMedCrossRefGoogle Scholar
  80. Narumi, S. and Maki, Y. (1978) Stimulatory effects of substance P on neurite extension and cyclic AMP levels in cultured neuroblastoma cells.J. Neurochem. 30, 1321–1326.PubMedCrossRefGoogle Scholar
  81. Nei, M. (1987)Molecular Evolutionary Genetics.Columbia University Press, New York.Google Scholar
  82. Nilsson, J., von Euler, A. M., and Dalsgaard, C.-J. (1985) Stimulation of connective tissue cell growth by substance P and substance K.Nature 315, 61–63.PubMedCrossRefGoogle Scholar
  83. Parker, I., Sumikawa, K., and Miledi, R. (1986) Neurotensin and substance P receptors expressed inXenopusoocytes by messenger RNA from rat brain.Proc. R. Soc. Lond. 229, 151–159.PubMedCrossRefGoogle Scholar
  84. Patacchini, R., Quartara, L., Rovero, P., Goso, C., and Maggi, C.A. (1993) Role of C-terminal amidation on the biological activity of neurokinin A derivatives with agonist and antagonist properties.J. Pharm. Exp. Ther. 264, 17–21.Google Scholar
  85. Quintana, J., Wong, H., and Ascoli, M. (1993) The regulation of the binding affinity of the luteinizing hormone/chorionic gonadotropin receptor by sodium ions is mediated by a highly conserved aspartate located in the second transmembrane domain of G-protein coupled receptor.Mol. Endocrin. 7, 767–775.CrossRefGoogle Scholar
  86. Regoli, D., Drapeau, G., Dion, S., and Couture, R. (1988) New selective agonists for neurokinin receptors: pharmacological tools for receptor characterization.Trends Pharmacol. Sci. 9, 290–295.PubMedCrossRefGoogle Scholar
  87. Regoli, D., Escher, E., Drapeau, G., D’Orleans-Juste, P., and Mizrahi, J. (1984) Receptors for substance P. III. classification by competitive antagonists.Eur..1. Pharmacol. 97, 179–189.CrossRefGoogle Scholar
  88. Rosell, S., Bjorkroth, U., Xu, J., and Folkers, K. (1983) The pharmacological profile of a substance P (SP) antagonist. Evidence for the existence of subpopulations of SP receptors.Acta Physiol. Scand. 117, 445–449.PubMedCrossRefGoogle Scholar
  89. Rouissi, N., Gitter, B. D., Waters, D. C., Howbert, J. J., Nixon, J. A,. and Regoli, D. (1991) Selectivity and specificity of new, nonpeptide, quinuclidine antagonists of substance P.Biochem. Biophys. Res. Comm. 176, 894–901.PubMedCrossRefGoogle Scholar
  90. Sachais, B. S., Snider, R M., Lowen III, J.A., and Krause, J. E. (1993) Molecular basis for the species selectivity of the substance P antagonist CP-96,345. J. Biol. Chem. 268, 2319–2323.PubMedGoogle Scholar
  91. Saffroy, M., Beauouan, J.-C., Torrens, Y., Besseyre, J., Bergstrom, L., and Glowinski, J. (1988) Localization of tachykinin binding sites (NK1, NK2, NK3 Ligands) in the rat brain.Peptides 9, 227–241.PubMedCrossRefGoogle Scholar
  92. Sandberg, B. E. B. (1985) Structure-activity relationships for substance P: a review, inSubstance P: Metabolism and Biological Actions(Jordan, C.C. and Oehme, P., eds.), Taylor and Francis, Philadelphia, PA, pp. 65–81.Google Scholar
  93. Sandberg, B. E. B. and Iversen, L. L. (1982) Substance P.J. Med. Chem. 25, 1009–1015.PubMedCrossRefGoogle Scholar
  94. Sasai, Y. and Nakanishi, S. (1989) Molecular characterization of rat substance K receptor and its mRNAs.Biochem. Biophys. Res. Commun. 165, 695–702.PubMedCrossRefGoogle Scholar
  95. Saviano, G., Temussi, P. A., Motta, A., Maggi, C. A., and Rovero, P. (1991) Conformation-activity relationship of tachykinin Neurokinin A (4–10) and of some [Xaa’] analogs. Biochemistry 30, 10,175–10,181.PubMedCrossRefGoogle Scholar
  96. Seamon, K. B. and Daly, J. W. (1983) Forskolin, cyclic AMP and cellular physiology.Trends Pharmacol. Sci. 4, 120–123.CrossRefGoogle Scholar
  97. Shigemoto, R., Yokota, Y., Tsuchida, K., and Nakanishi, S. (1990) Cloning and expression of a rat neuromedin K receptor cDNA.J. Biol. Chem. 265, 623–628PubMedGoogle Scholar
  98. Snider, R. M., Constantine, J. W., Lowe, J. A., et al. (1991) A potent nonpeptide antagonist of the substance P (NK1) receptor.Science 251, 435–437.PubMedCrossRefGoogle Scholar
  99. Sternweis, P.C. and Smrcka, A.V. (1992) Regulation of phospholipase C by G-proteins.Trends Biochem. Sci. 17, 502–506.PubMedCrossRefGoogle Scholar
  100. Strader, C. D., Candelore, M. R., Hill, W. S., Sigal, I. S., and Dixon, R. A. F. (1989) Identification of two serine residues involved in agonist activation of the betaadrenergic receptor.J. Biol. Chem. 264 13,572–13,578.PubMedGoogle Scholar
  101. Sugiya, H., Tennes, K. A., and Putney, J. W. Jr. (1987) Homologous desensitization of substance P induced inositol polyphosphate formation in rat parotid acinar cells.Biochem. J. 244, 647–653.PubMedGoogle Scholar
  102. Sumner, S. C. J. and Ferretti, J. A. (1989) Conformational behavior of the linear hexapeptide senktide: a receptor specific tachykinin analog.FEBS Lett. 253, 117–120.PubMedCrossRefGoogle Scholar
  103. Sundelin, J. B., Provendini, D. M., Wahlestedt, C. R., Pohl, J. S., and Peterson, P. A. (1992) Molecular cloning of the murine substance K and substance P receptor genes.Eur. J. Biochem. 203, 625–631.PubMedCrossRefGoogle Scholar
  104. Tachado, S.D., Akhtar, R. A., Yousufazai, S. Y. K., and Abdel-Latif, A. A. A. (1991) Species differences in the effects of substance P on inositol trisphosphate accumulation and cyclic AMP formation, and on contraction in isolated iris sphincter of the mammalian eye: Differences in receptor density.Exp. Eye Res. 53, 729–739.PubMedCrossRefGoogle Scholar
  105. Takahashi, K., Tanaka, A., Hara, M., and Nakanishi, S. (1992) The primary structure and gene organization of human substance P and neuromedin K receptors.Eur. J. Biochem. 204, 1025–1033.PubMedCrossRefGoogle Scholar
  106. Takeda, Y., Blount, P., Sachais, B. S., Hershey, A. D., Raddatz, R., and Krause, J. E. (1992) Ligand binding and kinetics of substance P and neurokinin A receptors stably expressed in Chinese hamster ovary cells and evidence for differential stimulation of inositol 1,4,5-trisphosphate and cyclic AMP second messenger responses.J. Neurochem. 59, 740–745.PubMedCrossRefGoogle Scholar
  107. Takeda, Y. and Krause, J. E. (1991) Pharmacological and molecular biological studies on the diversity of rat tachykinin NK-2 receptor subtypes in rat CNS, duodenum, vas deferens, and urinary bladder, inSubstance P and Related Peptides(Leeman, S. E., Krause, J. E., and Lembeck, F., eds.),Ann. NY Acad. Sci., New York, 632, 479–482.Google Scholar
  108. 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. Comm. 179, 1232–1240.PubMedCrossRefGoogle Scholar
  109. Tjolsen, A., Berge, 0.-G., Hunskaar, S., Rosland, J. H., and Hole, K. (1992) The formalin test: an evaluation of the method.Pain 51, 5–17.PubMedCrossRefGoogle Scholar
  110. Torrens, Y., Daguet de Montety, M. C., El Etr, M., Beaujouan, J-C., and Glowinski, J. (1989) Tachykinin receptors of the NK-1 type (substance P) coupled positively to phospholipase C on cortical astrocytes from the newborn mouse in primary culture.J. Neurochem. 52, 1913–1918.PubMedCrossRefGoogle Scholar
  111. Torrens, Y., Lavielle, S., Chassaing, G., Marquet, A., Glowinski, J., and Beaujouan, J. C. (1984) Neuromedin K, a tool to further distinguish two central tachykinin binding sites.Eur. J. Pharmacol. 102, 381,382.Google Scholar
  112. Tsuchida, K., Shigemoto, R., Yokota, Y., and Nakanishi, S. (1990) Tissue distribution and quantitation of the mRNA for three rat tachykinin receptors.Eur. J. Biochem. 193, 751–757.PubMedCrossRefGoogle Scholar
  113. Tsutsumi, M., Zhou, W., Millar, R. P., Mellon, P. L., Roberts, J. L., Flanagan, C. A., Dong, K., Boaz, G., and Selfon, S.C. (1992) Cloning and functional expression of a mouse gonadotropin releasing hormone receptors.Mol. Endo. 6, 1163–1169.CrossRefGoogle Scholar
  114. 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 cells.Proc. Natl. Acad. Sci. USA 88, 1661–1665.PubMedCrossRefGoogle Scholar
  115. Venepalli, B. R., Aimone, L. D., Appel, K. C., Bell, M. R., Dority, J. A., Goswami, R., Hall, P.L., Kumar, V., Lawrence, K. B., Logan, M. E., Scensny, P. M., Seelye, J. A., Tomczuk, B. E., and Yanni, J. M. (1992) Synthesis and substance P receptor binding activity of androstano[3,2-b]pyrymido[1,2-a]benzimidizoles.J. Med. Chem. 35, 374–378.PubMedCrossRefGoogle Scholar
  116. Ward, P., Ewan, G. B., Jordan, C. C., Ireland, S. J., Hagan, R. M., and Brown, J. R. (1990) Potent and highly selective neurokinin antagonists.J. Med. Chem. 33, 1848–1851.PubMedCrossRefGoogle Scholar
  117. Watling, K. J. and Krause, J. E. (1993) The rising sun shines on substance P and related peptides.Trends Pharm. Sci. 14, 81–84.PubMedCrossRefGoogle Scholar
  118. Watson S. (1984) The action of substance P on contraction, inositol phospholipids, and adenylate cyclase in rat small intestine.Biochem. Pharmacol. 33, 3733–3737.PubMedCrossRefGoogle Scholar
  119. Watson, S. P., Sandberg, B. E. B., Hanley, M. R., and Iversen, L. L. (1983) Tissue selectivity of substance P alkyl esters: suggestive of multiple receptors.Eur. J. Pharmacol. 87, 77–84.PubMedCrossRefGoogle Scholar
  120. Wormser, U., Laufer, R., Hart, Y., Chorev, M., Gilon, C., and Selinger, Z. (1986) Highly selective agonists for substance P receptor subtypes.EMBO J. 5, 2805–2808.PubMedGoogle Scholar
  121. Wu, D., Katz, A., and Simon, M. I. (1993) Activation of phospholipase Cß2by the a and ß subunits of trimeric GTP-binding protein.Proc. Natl. Acad. Sci. USA 90, 5297-5301.CrossRefGoogle Scholar
  122. Xie, G.-X., Miyajima, A., and Goldstein, A. (1992) Expression cloning of cDNA encoding a seven-helix receptor from human placenta with affinity for opioid ligands.Proc. Natl. Acad. Sci. USA 89, 4124–4128.PubMedCrossRefGoogle Scholar
  123. Yamachita, K., Koide, Y., and Aiyochi, Y. (1983) Effects of substance Pon thyroidal cyclic AMP levels and thyroid hormone from canine thyroid slices.Life Sci. 32, 2163–2166.CrossRefGoogle Scholar
  124. Yashpal, K., Radhakrishnan, V., Coderre, T. J., and Henry, J. L. (1993) CP-96,345, but not its stereoisomer, CP-96,344, blocks the nociceptive responses to intrathecally administered substance P and to noxious thermal and chemical stimuli in the rat.Neuroscience 52, 1039–1047.PubMedCrossRefGoogle Scholar
  125. Yokota, Y., Sasai, Y., Tanaka, K., Fiiwana, T., Tsuchida, K., Shigemoto, R., Kakizuka, A., Ohkubo, H., and Nakanishi, S. (1989) Molecular characterization of a functional cDNA for rat substance P receptor.J. Biol. Chem. 264, 17,649–17,652.PubMedGoogle Scholar
  126. Yokota, Y., Akazawa, C., Ohkubo, H., and Nakanishi, S. (1992) Delineation of structural domains involved in the subtype specificity of tachykinin receptors through chimeric formation of substance P/substance K receptors.EMBO J. 11 3585–3591.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • James E. Krause
  • Paul Blount
  • Bruce S. Sachais

There are no affiliations available

Personalised recommendations