Alterations in Receptors for Sensory Neuropeptides in Human Inflammatory Bowel Disease

  • P. W. Mantyh
  • M. Catton
  • J. E. Maggio
  • S. R. Vigna
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 298)


Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. We have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in two human inflammatory diseases, ulcerative colitis and Crohn’s disease, using quantitative receptor autoradiography. The sensory neurotransmitter receptors included bombesin, calcitonin gene-related peptide-α, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only binding sites for substance P and vasoactive intestinal peptide were significantly altered in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues.


Ulcerative Colitis Sensory Neuron Vasoactive Intestinal Peptide Vasoactive Intestinal Polypeptide Ulcerative Colitis Patient 
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.









blood vessel (arteriole or venule)




calcitonin gene-related peptide-α


circular muscle of the muscularis externa


connective tissue


germinal layer of a lymph nodule






hematoxylin and eosin


longitudinal muscle of the muscularis externa




lymph nodule




— b mucosa, basal aspect


— l mucosa, luminal aspect


muscularis mucosa


myenteric plexus




proliferative zone of a lymph nodule


substance K, neurokinin A, α-neurokinin, neuromedin L




substance P




ulcerative colitis


vasoactive intestinal peptide


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Almy, T., 1980, Psychosocial aspects of chronic ulcerative-colitis and Crohn’s disease, in: “Inflammatory Bowel Disease”, J.B. Kirsner and R.G. Shorter, eds., Lea and Fibiger, Philadelphia.Google Scholar
  2. 2.
    Bar-Shavit, Z., Goldman, R., Stabinsky, Y., Gottlieb, P., Fridkin, M., Teichberg, V.I. and Blumberg, S., 1980, Enhancement of phagocytosis: a newly found activity for substance P residing in its N-terminal tetrapeptide sequence, Biochem. Biophys. Res. Commun., 94:1445.PubMedCrossRefGoogle Scholar
  3. 3.
    Bartho, L., and Holzer, P., 1985, Search for a physiological role of substance P in gastrointestinal motility, Neuroscience, 16:1.PubMedCrossRefGoogle Scholar
  4. 4.
    Bayliss, V.M., 1901, On the origin from the spinal cord of the vasodilator fibres of the hind limb, and on the nature of these fibres, J. Physiol. (Lond), 26:173.Google Scholar
  5. 5.
    Benjamin, N., Collery, C. T., Fuller, R. W., Larkin, S., and McEwan, S., 1987, The effects of calcitonin gene-related peptide and substance P on resistance and capacitance vessels, Br. J. Pharmacol., 90:39 (abstract).Google Scholar
  6. 6.
    Beuerman, R.W., and Schimmelpfennig, B., 1980, Sensory denervation of the rabbit cornea affects epithelial properties, Exp. Neurol., 69:196.PubMedCrossRefGoogle Scholar
  7. 7.
    Bishop, A. E., Polak, J. M., Bryant, M. G., Bloom, S. R., and Hamilton, S., 1980, Abnormalities of vasoactive intestinal polypeptide-containing nerves in Crohn’s disease, Gastroenterology, 9:853.Google Scholar
  8. 8.
    Brimijoin, S., Lundberg, J. M., Brodin, E., Hokfelt, T., and Nilsson, G., 1980, Axonal transport of substance P in the vagus and sciatic nerves of the guinea pig, Brain Res., 191:443.PubMedCrossRefGoogle Scholar
  9. 9.
    Buck, S.H., and Burks, T.F., 1983, Capsaicin; hot new pharmacological tool, Trends Pharm. Sci., 4:84.CrossRefGoogle Scholar
  10. 10.
    Burcher, E., Buck, S. H., Lovenberg, W., and O’Donohue T. L., 1986, Characterization and autoradiographic localization of multiple tachykinin binding sites in gastrointestinal tract and bladder, J. Pharm. Exp. Ther., 236:819.Google Scholar
  11. 11.
    Burcher, E., Shults, C. W., Buck, S. H., Chase, T. N., and O’Donohue, T.L., 1984, Autoradiographic distribution of substance K binding sites in rat gastrointestinal tract: a comparison with substance P, Eur. J. Pharm., 102:561.CrossRefGoogle Scholar
  12. 12.
    Colpaert, F. C., Donnerer, J., and Lembeck, F., 1983, Effects of capsaicin on inflammation and on the substance P content of nervous tissues in rats with adjuvant arthritis, Life Sci., 32:1827.PubMedCrossRefGoogle Scholar
  13. 13.
    Corey, L., and Spear, P.G., 1986, Infections with herpes simplex viruses, N. Engl. J. Med., 314:686.PubMedCrossRefGoogle Scholar
  14. 14.
    Cowan, W.M., Gottlieb, D.I., Hendrickson, A.E., Price, J.L., and Woolsey, T.A., 1972, The autoradiographic demonstration of axonal connections in the central nervous system, Brain Res., 37:21.PubMedCrossRefGoogle Scholar
  15. 15.
    Dale, H.H., 1935, Walter Ernest Dixon Memorial Lecture, Proc. R. Soc. Med. Therap., Sec.28:319.Google Scholar
  16. 16.
    Dalsgaard, C. J., Haegerstrand, A., Theodorsson-Norheim, E., Brodin, E., and Hokfelt, T., 1985, Neurokinin A-like immuno-reactivitiy in rat primary sensory neurons: coexistence with substance P, Histochemistry, 83:37.PubMedCrossRefGoogle Scholar
  17. 17.
    Dalsgaard, C. J., Vincent, S. R., Hokfelt, T., Lundberg, J. M., Dahlstrom, A., Schultzberg, M., Dockray, C.J., and Cuello, A.C., 1982, Co-existence of cholecystokinin- and substance P-like peptides in neurons of the dorsal root ganglion of the rat, Neurosci. Lett., 33:159.PubMedCrossRefGoogle Scholar
  18. 18.
    Debiasi, S., Vaneyck, S.L., Petrusz, P., and Rustioni, A., 1987, Glutamate and substance P co-exist in the same primary afferent terminal in the superficial laminae of the rat spinal dorsal horn, Neurosci. Abstr., 13:434.Google Scholar
  19. 19.
    Devillier, P., Weill, B., Renoux, M., Menkes, C., and Pradelles, P., 1987, Elevated levels of tachykinin-like immunoreactivity in joint fluids from patients with rheumatic inflammatory diseases, N. Engl. J. Med., 314:1323.Google Scholar
  20. 20.
    Eccles, J. C., 1957, “The Physiology of Nerve Cells,” Johns Hopkins Press, Baltimore.Google Scholar
  21. 21.
    Foreman, J., and Jordan, C., 1983, Histamine release and vascular changes induced by neuropeptides, Agents Actions, 13:105.PubMedCrossRefGoogle Scholar
  22. 22.
    Franco, R., Costa, M., and Furness, J.B., 1979a, Evidence for the release of endogenous substance P from intestinal nerves, Naunyn-Schmiedeberg’s Arch. Pharmacol., 301:195.Google Scholar
  23. 23.
    Franco, R., Costa, M., and Furness, J.B., 1979b, Evidence that axons containing substance P in the guinea-pig ileum are of extrinsic origin, Naunyn-Schmiedeberg’s Arch. Pharmacol., 307:57.CrossRefGoogle Scholar
  24. 24.
    Furness, J., Papka, R. E., Delia, N. G., Costa, M., and Eskay, R.L., 1982, Substance P-like immunoreactivity in nerves associated with the vascular system of guinea-pigs, Neuroscience, 7:447.PubMedCrossRefGoogle Scholar
  25. 25.
    Gallin, J. I., and Fauci, A. S., 1982, “Advances in Host Defense Mechanisms,” Vol. 1 Phagocytic Cells, Raven Press, New York.Google Scholar
  26. 26.
    Gamse, R., Holzer, P., and Lembeck, F., 1980, Decrease of substance P in primary afferent neurons and impairment of neurogenic plasma extravasation by capsaicin, Br. J. Pharmac, 68:207.CrossRefGoogle Scholar
  27. 27.
    Gaudreau, P., Quirion, R., St. Pierre, S., and Pert, C.B., 1983, Characterization and visualization of cholecystokinin receptors in rat brain using [3H]pentagastrin, Peptides, 4:755.PubMedCrossRefGoogle Scholar
  28. 28.
    Gibbs, I. L., Furness, J.B., Costa, M., MacIntyre, I., Hillyard, C.J., and Girgis, S., 1985, Colocalization of calcitonin gene-related peptide-like immunoreactivity with substance P in cutaneous, vascular and visceral sensory neurons of guinea pigs, Neurosci. Lettr., 57:125.CrossRefGoogle Scholar
  29. 29.
    Goedert, M., Mantyh, P. W., Emson, P. C., and Hunt, S. P., 1984, Inverse relationship between neurotensin receptors and neurotensin-like immunoreactivity in the cat striatum, Nature, 307:543.PubMedCrossRefGoogle Scholar
  30. 30.
    Greenamyre, J.T., Young, A. B., and Penney, J. B., 1983, Quantitative autoradiography of L-[3H]glutamate binding in rat brain, Neurosci. Lett., 37:155.PubMedCrossRefGoogle Scholar
  31. 31.
    Greenamyre, J.T., Young, A. B., and Penney, J. B., 1983, Quantitative autoradiography distribution of L-[3H]glutamate binding sites in rat central nervous system, J. Neurosci., 8:2133.Google Scholar
  32. 32.
    Hartung, H. P., and Toyka, K.V., 1983, Activation of macrophages by substance P: induction of oxidative burst and thromboxane release, Eur. J. Pharmacol., 89:301.PubMedCrossRefGoogle Scholar
  33. 33.
    Hartung, H. P., Wolters, K., and Toyka, K.V., 1986, Substance P: binding properties and studies on cellular responses in guinea pig macrophages, J. Immunol., 136:856.Google Scholar
  34. 34.
    Herkenham, M., 1987, Mismatches between neurotransmitter and receptor localization in brain: observations and implications, Neuroscience, 23:1.PubMedCrossRefGoogle Scholar
  35. 35.
    Hokfelt, T., Johansson, O., Ljungdalh, A., Lundberg, J.M., and Schultzberg, M., 1980, Peptidergic neurons, Nature, 284:515.PubMedCrossRefGoogle Scholar
  36. 36.
    Hokfelt, T., Jellerth, 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.PubMedCrossRefGoogle Scholar
  37. 37.
    Hua, X. Y., Theodorsson-Norheim, E., Brodin, E., Lundberg, J.M., and Hokfelt, T., 1985, Multiple tachykinins, neurokinin A, neuropeptide K and substance P) in capsaicin-sensitive sensory neurons in the guinea pig, Regulatory Peptides, 13:1.PubMedCrossRefGoogle Scholar
  38. 38.
    Hylden, J.L.K., and Wilcox, G. L., 1981, Intrathecal substance P elicits a caudally directed biting and scratching behavior in mice, Brain Res., 217:212.PubMedCrossRefGoogle Scholar
  39. 39.
    Jansco, N.A., Jansco-Gabor, A., and Szolcsanyi, J., 1967, Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin, Br. J. Pharmacol., 31:138.Google Scholar
  40. 40.
    Jansco, N. A., Jansco-Gabor, A., and Szolcsanyi, J., 1968, The role of sensory nerve endings in neurogenic inflammation induced in human skin and in the eye and paw of the rat, Br. J. Pharmac, 32:32.Google Scholar
  41. 41.
    Jansco, N. A., Kiraly, E., and Jansco-Gabor, A., 1980, Pharmacologically induced elective degeneration of chemosensitive primary sensory neurons, Nature, 270:741.Google Scholar
  42. 42.
    Jansco, N.A., Kiraly, E., and Jansco-Gabor, A., 1980, Chemosensitive pain fibers and inflammation, Int. J. Tiss. Reac., 2:57.Google Scholar
  43. 43.
    Jessel, T.M., and Iversen, L.L., 1977, Opiate analgesics inhibit substance P release from rat trigeminal nucleus, Nature, 268:549.CrossRefGoogle Scholar
  44. 44.
    Johnson, A. R., and Erdos, E.G., 1973, Release of histamine from mast cells by vasoactive peptides, Proc. Soc. Exp. Biol. Med., 142:1252.PubMedGoogle Scholar
  45. 45.
    Ju, G., Hokfelt, T., Brodin, E., Fahrenkrug, J., Fischer, J. A., Frey, P., Elde, R.P., and Brown, J.C., 1987, Primary sensory neurons of the rat showing calcitonin gene-related peptide immunoreactivity and their relation to substance P-, somatostatin-, galanin-, vasoactive intestinal peptide- and cholecystokinin-immunoreactive ganglion cells, Cell Tissue Res., 247:417.PubMedCrossRefGoogle Scholar
  46. 46.
    Koch, T.R., Carney, J.A., and Go, V.L.W., 1987, Distribution and quantitation of gut neuropeptides in normal intestine and inflammatory bowel diseases, Dig. Diseases and Sciences, 32.369.CrossRefGoogle Scholar
  47. 47.
    Kuhar, M. J., 1985, The mismatch problem in receptor mapping studies, Trends Neurosci., 8:190.CrossRefGoogle Scholar
  48. 48.
    Langley, J. N., 1923, Antidromic action, J. Physiol.(Lond), 57:428.Google Scholar
  49. 49.
    Lembeck, F., Donnerer, J. and Colpaert, F. C., 1981, Increase of substance P in primary afferent nerves during chronic pain, Neuropeptides, 1:175.CrossRefGoogle Scholar
  50. 50.
    Lembeck, F., and Holzer, P., 1979, Substance P as a neurogenic mediator of antidromic vasodilatation and neurogenic plasma extravasation, Naunyn-Schmiedeberg’s Arch. Pharmacol., 310:175.CrossRefGoogle Scholar
  51. 51.
    Levine, J. D., Clark, R., Devor, M., Helms, C., Moskowitz, M.A., Basbaum, A.I., 1985, Intraneuronal substance P contributes to the severity of experimental arthritis, Science, 226:547.CrossRefGoogle Scholar
  52. 52.
    Levine, J.D., Collier, D.H., Basbaum, A.I., Moskowitz, M.A., and Helms, C.A., 1985, Hypothesis: the nervous system may contribute to the pathophysiology of rheumatorid arthritis, J. Rheumatology, 12:410.Google Scholar
  53. 53.
    Levine, J. D., Dardick, S. J., Roizen, M. F., Helms, C., and Basbaum, A.I., 1986, Contribution of sensory afferents and sympathetic efferents to joint injury in experimental arthritis, J. Neurosci., 6:3423.PubMedGoogle Scholar
  54. 54.
    Lewis, T., and Marvin, H. M., 1927, Observations relating to vasodilatation arising from antidromic impulses, to herpes zoster and trophic effects, Heart, 14:27.Google Scholar
  55. 55.
    Llewellyn-Smith, I.J., Furness, J.B., Murphy, R., O’Brien, P.E., and Costa, M., 1984, Substance P-containing nerves in the human small intestine: distribution, ultrastructure, and characterization of the immunoreactive peptide, Gastroenterology, 86:421.PubMedGoogle Scholar
  56. 56.
    Lotz, M., Carson, D.A., Vaughan, J.H.,, 1987, Substance P activation of rheumatoid synoviocytes: Neural pathway in pathogenesis of arthritis, Science, 235:893.PubMedCrossRefGoogle Scholar
  57. 57.
    Lundberg, J.M., Brodin, E., Hua, X., and Saria, A., 1984, Vascular permeability changes and smooth muscle contraction in relation to capsaicin-sensitive substance P afferents in the guinea pig, Acta Physiol. Scand., 120:217.PubMedCrossRefGoogle Scholar
  58. 58.
    Lundberg, J. M., Franco-Cereceda, A., Hua, X., Hokfelt, T., and Fischer, J.A., 1985, Co-existence of substance P and calcitonin gene-related peptide-like immunoreactivities in sensory nerves in relation to cardiovascular and broncho-constrictor effects of capsaicin, Eur. J. Pharmacology, 108:315.CrossRefGoogle Scholar
  59. 59.
    Lundberg, J.M., and Saria, A., 1983, Capsaicin-induced de-sensitization of the airway mucosa to cigarette smoke, mechanical and chemical irritants, Nature, 302:251.PubMedCrossRefGoogle Scholar
  60. 60.
    Maggio, J.E., 1988, Tachykinins, Ann. Rev. Neurosci., 11:13.PubMedCrossRefGoogle Scholar
  61. 61.
    Maggio, J. E., and Hunter, J. C., 1984, Regional distribution of kassinin-like immunoreactivity in rat central and peripheral tissues and the effect of capsaicin, Brain Res., 307:370PubMedCrossRefGoogle Scholar
  62. 62.
    Mantyh, C. R., Gates, T. S., Zimmerman, R. P., Welton, M. L., Passaro, E.P.Jr., Vigna, S.R., Maggio, J.E., Kruger, L., and Mantyh, P.W., 1988, 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, Proc. Natl. Acad. Sci., 85:3235.PubMedCrossRefGoogle Scholar
  63. 63.
    Mantyh, C. R., and Mantyh, P.W., 1985, Differential localization of cholecystokinin-8 binding sites in the rat vs the guinea pig brain, Eur. J. Pharmacol., 113:37.CrossRefGoogle Scholar
  64. 64.
    Mantyh, P. W., 1988, Autoradiographic localization and characterization of receptor binding sites in the brain and peripheral tissues, in: “Receptor Biochemistry and Methodology: Receptor Localization, Ligand Autoradiography,” Vol. 13, F.M. Leslie and C.A. Altar, eds., A.R. Liss, New York.Google Scholar
  65. 65.
    Mantyh, P.W., Goedert, M., and Hunt, S. P., 1984a, Autoradiographic visualization of receptor binding sites for substance P in the gastrointestinal tract of the guinea pig, Eur. J. Pharm., 100:133.CrossRefGoogle Scholar
  66. 66.
    Mantyh, P.W., and Hunt, S.P., 1985a, Autoradiographic visualization of [3H]-Substance P receptor binding sites in the rat and bovine spinal cord and the rat and cat spinal trigeminal nucleus pars caudalis and the effects of neonatal capsaicin, Brain Res., 332:315.PubMedCrossRefGoogle Scholar
  67. 67.
    Mantyh, P. W., and Hunt, S. P., 1986, Changes in 3H-substance P receptor binding sites in the rat brain after kia-nic lesion of the corpus striatum, J. Neurosci., 6:1537.PubMedGoogle Scholar
  68. 68.
    Mantyh, P. W., Hunt, S. P. and Maggio, J. E., 1984b, Substance P receptors: localization by light microscopic auto-radiograph in rat brain using [3H]-SP as the radioligand, Brain Res., 307:147.PubMedCrossRefGoogle Scholar
  69. 69.
    Mantyh, P. W., Maggio, J. E., and Hunt, S. P., 1984c, The autoradiographic distribution of kassinin and substance K binding sites is different from the distribution of substance P binding sites in the rat brain, Eur. J. Pharmacol., 102:361.PubMedCrossRefGoogle Scholar
  70. 70.
    Mantyh, P. W., Mantyh, C. R., Brecha, N. C., Kruger, L., and Sternini, C., 1985b), Autoradiographic localization of calcitonin gene-related peptide binding sites in the rat brain, guinea pig periphery and human spinal cord, Neurosci. Abstr., 11:145.Google Scholar
  71. 71.
    Mantyh, P. W., Mantyh, C.R., Gates, T., Vigna, S.R., and Maggio, J.E., 1988, Receptor binding sites for substance P and substance K in the Canine gastrointestinal tract and their possible role in inflammatory bowel disease, Neuroscience, 25:817.PubMedCrossRefGoogle Scholar
  72. 72.
    Mantyh, P.W., Mantyh, C. R., and Maggio, J. E., 1987a, Heterogeneity of tachykinin receptors, in: “Substance P and Neurokinins,” James L. Henry, ed., Springer-Verlag, New York (in press).Google Scholar
  73. 73.
    Mantyh, P.W., Mantyh, C.R., Popper, P., Vigna, S.R., Kruger, L., Basbaum, A.I., Levine, J.D., and Maggio, J.E., 1987b, Receptors for sensory neuropeptides may be involved in the pathophysiology of rheumatoid arthritis, Soc. Neurosci. Abstr., 13:563.Google Scholar
  74. 74.
    Mantyh, P. W., Pinnock, R. D., Downes, C. P., Goedert, M., and Hunt, S.P., 1984d, Substance P receptors: correlation with substance P induced inositol phospholipid hydrolysis in the rat central nervous system, Nature, 309:795.PubMedCrossRefGoogle Scholar
  75. 75.
    Marasco, W. A., Showell, H.J., and Becker, E.L., 1981, Substance P binds to the formaldehyde Chemotaxis receptor on the rabbit neutrophil, Biochem. Biophys. Res. Comm., 99:1065.PubMedCrossRefGoogle Scholar
  76. 76.
    Massari, V.J., Shults, C.W., Park, C.., Tizabi, Y., Moody, T.W., Chronwall, B.M., Culver, M., and Chase, T.N., 1985, Deafferentation causes a loss of presynaptic bombesin receptors and supersensitivity of substance P receptors in the dorsal horn of the cat spinal cord, Brain Res., 343:268.PubMedCrossRefGoogle Scholar
  77. 77.
    Maurer, R., and Reubi, J. C., 1985, Brain somatostatin receptor subpopulation visualized by autoradiography, Brain Res., 333:178.PubMedCrossRefGoogle Scholar
  78. 78.
    Mazurek, N., Pecht, I., Teichberg, V.l., and Blumberg, S., 1981, The role of the N terminal tetrapeptide in the histamine-releasing action of substance P, Neuropharmacol., 20:1025.CrossRefGoogle Scholar
  79. 79.
    McGillis, J.P., Organist, M.L., and Payan, D.G., 1987, Substance P and immunoregulation, Fed. Proc, 46:196.PubMedGoogle Scholar
  80. 80.
    Melander, T., Hokfelt, T., Nilsson, S., and Brodin, E., 1986, Visualization of galanin binding sites in the rat central nervous system, Eur. J. Pharm., 124:381.CrossRefGoogle Scholar
  81. 81.
    Mendeloff, A. I., 1980, Epidemiology of idiopathic inflammatory bowel disease, in: “Inflammatory Bowel Disease,”, J.B. Kirsner and R.G. Shorter, eds., Lea and Fibiger, Philadelphia.Google Scholar
  82. 82.
    Moody, T.W., O’Donohue, T. L., and Jacobowitz, D. M., 1981, Biochemical localization and characterization of bombesin-like peptides in discrete regions of the rat brain, Peptides, 2:75.PubMedCrossRefGoogle Scholar
  83. 83.
    Mulderry, P. K., Ghatei, M. A., Spokes, R. A., Jones, P. M., Pierson, A.M., Hamic, Q.A., Kanse, S., Amara, S.G., Burrin, J.M., Legon, S., Polak, J.M., and Bloom, S.R., 1988, Differential expression of α-CGRP and β-CGRP by primary sensory neurons and enteric autonomic neurons of the rat, Neuroscience, 25:195.PubMedCrossRefGoogle Scholar
  84. 84.
    Nagy, J. I., Hunt, S. P., Iversen, L. L., and Emson, P.C., 1981, Biochemical and anatomical observations on the degeneration of peptide-containing primary afferent neurons after neonatal capsaicin, Neuroscience, 6:1923.PubMedCrossRefGoogle Scholar
  85. 85.
    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.PubMedCrossRefGoogle Scholar
  86. 86.
    Oku, R., Saton, M., Takagi, H., 1987, Release of substance P from the spinal dorsal horn is enhanced in polyarthritic rats, Neurosci. Lett., 74:315.PubMedCrossRefGoogle Scholar
  87. 87.
    O’Morain, C., Bishop, A. E., McGregor, G. P., Levi, A.J., Bloom, S.R., Polak, J.M., and Peters, T.J., 1984, Vasoactive intestinal peptide concentrations and immunocytochemical studies in rectal biopsies from patients with inflammatory bowel disease, Gut, 25:56.Google Scholar
  88. 88.
    Orleans-Juste, D’P., Dion, S., Mizrahi, J., and Regoli, D., 1985, Effects of peptides and non-peptides on isolated arterial smooth muscles: role of endothelium, Eur. J. Pharmacol., 114:9.PubMedCrossRefGoogle Scholar
  89. 89.
    Payan, D. F., Brewster, D. R., and Goetzl, E. J., 1983, Specific stimulation of human T-lymphocytes by substance P, J. Immunol., 131:1613.PubMedGoogle Scholar
  90. 90.
    Payan, D.G., McGillis, J. P., and Goetzl, E. J., 1986, Neu-roimmunology, Adv. Immunol., 39:299.PubMedCrossRefGoogle Scholar
  91. 91.
    Payan, D.G., McGillis, J.P., Organist, M.L., 1986, Binding characteristics and affinity labeling of protein consituents of the human IM-9 lymphoblast receptor for substance P, J. Biol. Chem., 261:14321.PubMedGoogle Scholar
  92. 92.
    Pernow, B., 1983, Substance P, Pharmacol. Rev., 35:85.PubMedGoogle Scholar
  93. 93.
    Pernow, B., 1985, Role of tachykinins in neurogenic inflammation, J. Immunol., 135:812s.Google Scholar
  94. 94.
    Piotrowski, W., Devoy, M.A.B., Jordan, C. C., and Foremen, J.C., 1984, The substance P receptor on rat mast cells and in human skin, Agents and Actions, 14:420.PubMedCrossRefGoogle Scholar
  95. 95.
    Popper, P., Mantyh, C.R., Vigna, S.R., Maggio, J.E., and Mantyh, P.W., 1988, The localization of sensory nerve fibers and receptor binding sites for sensory neuropeptides in canine mesenteric lymph nodes, Peptides, 9:257.PubMedCrossRefGoogle Scholar
  96. 96.
    Rainbow, T. C., Biegon, A., and Berck, D.J., 1984, Quantitative receptor autoradiography with tritium labeled ligands: comparison of biochemical and densitometric measurements, J. Neurosci. Methods, 11:231.PubMedCrossRefGoogle Scholar
  97. 97.
    Reubi, J.C., Corete, R., Maurer, R., Probst, A., Palacios, J.M., 1986, Distribution of somatostatin receptors in the human brain: an autoradiographic study, Neuroscience, 18:329.PubMedCrossRefGoogle Scholar
  98. 98.
    Reubi, J. C., Probst, A., Cortes, R., and Palacios, J. M., 1987, Distinct topographical localization of two somatostatin receptor subpopulations in the human cortex, Brain Res., 406:391.PubMedCrossRefGoogle Scholar
  99. 99.
    Roberts, A. B., Anzano, M.A., Wakefield, L.M., Roche, N., Stern, D.F., and Sporn, M.B., 1985, Type beta transforming growth factor: a bifunctional regulator of cellular growth, Proc. Natl. Acad. Sci., 82:119.PubMedCrossRefGoogle Scholar
  100. 100.
    Rosenberg, I. H., 1985, Inflammatory bowel disease, in: “Cecil Textbook of Medicine,” J.B. Wyngaarden and L.H. Smith, eds., W.B. Saunders, Philadelphia.Google Scholar
  101. 101.
    Rozsa, Z., Jancso, G., and Varro, V., 1984, Possibile involvement of capsaicin-sensitive sensory nerves in the regulation of intestinal blood flow in the dog, Naunyn-Schmiedeberg’s Arch. Pharmacol., 326:352.CrossRefGoogle Scholar
  102. 102.
    Ruff, M. R., Wahl, S. M., and Pert, C. B., 1985, Substance P receptor-mediated Chemotaxis of human monocytes, Peptides, 6(suppl.2):107.PubMedCrossRefGoogle Scholar
  103. 103.
    Schaffer, M.M., and Moody, T. W., 1986, Autoradiographic visualization of CNS receptors for vasoactive intestinal peptide, Peptides, 7:283.CrossRefGoogle Scholar
  104. 104.
    Schulzberg, T., Hokfelt, T., Nilsson, G., Terenius, L., Rehfeld, J.F., Brown, M., Elde, R., Goldstein, M., and Said, S., 1980, Distribution of peptide- and catecholamine containing neurons in the gastrointestinal tract of rat and guinea pig: Immunohistochemical studies with antisera to substance P, vasoactive intestinal polypeptide, enkephalins, somatostatin, gastrin/cholecystokinin, neurotensin and dopamine B-hydroxylase, Neuroscience, 5:689.CrossRefGoogle Scholar
  105. 105.
    Sjolund, K., Schaffalitzky De Muckadell, O. B., Fahrenkrug, J., Hakanson, R., Peterson, B.G., and Sundler, F., 1983, Peptide-containing nerve fibers in the gut wall in Crohn’s disease, Gut, 24:724.PubMedCrossRefGoogle Scholar
  106. 106.
    Skofitsch, G., and Jacobowitz, D. M., 1985a, Autoradiographic distribution of 125I-calcitonin gene-related peptide binding sites in the rat central nervous system, Peptides, 4:975.CrossRefGoogle Scholar
  107. 107.
    Skofitsch, G., and Jacobowitz, D. M., 1985b, Calcitonin gene-related peptide coexists with substance P in capsaicin-sensitive neurons and sensory ganglia of the rat, Peptides, 6:747.PubMedCrossRefGoogle Scholar
  108. 108.
    Sporn, M. B., and Roberts, A. B., 1988, Peptide growth factors are multifunctional, Nature, 332:217.PubMedCrossRefGoogle Scholar
  109. 109.
    Stanisz, A.M., Befus, D., and Bienenstock, J., 1986, Differential effects of vasoactive intestinal peptide, substance P and somatostatin on immunoglobulin synthesis and proliferation by lymphocytes from Peyer’s patches, mesenteric lymph nodes and spleen, J. Immunol., 136:152.PubMedGoogle Scholar
  110. 110.
    Stephenson, J.A., Burcher, E., and Summers, R. J., 1986. Autoradiographic demonstration of endothelium-dependent [125I] Bolton-Hunter substance P binding to dog carotid artery, Eur. J. Pharmacol., 124:377.PubMedCrossRefGoogle Scholar
  111. 111.
    Stricker, S., 1876, Untersuchungen uber die Gefasswurzeln dis Ischiadicus, Stitz. Ber. Kaiserl. Akad. Wiss. (Wein), 3:173.Google Scholar
  112. 112.
    Su, H. C., Bishop, A. E., Power, R. F., Hamada, Y., and Polak, J.M., 1987, Dual intrinsic and extrinsic origins of CGRP- and NPY-immunoreactive nerves of rat gut and pancreas, J. Neurosci., 9:2674.Google Scholar
  113. 113.
    Svensjo, E., Lundberg, J. M., Anggard, A., and Hokfelt, T., 1980, Substance P increase in vascular permeability and presence in the hamster cheek pouch, J. Microvascular Res., 20:38.Google Scholar
  114. 114.
    Tange, A., 1983, Distribution of peptide-containing endocrine cells and neurons in the gastrointestinal tract of the dog: immunohistochemical studies using antisera to somatostatin, substance P, vasoactive intestinal polypeptide, Met-enkephalin and neurotensin, Biomed. Res., 4:9.Google Scholar
  115. 115.
    Tschopp, F.A., Henke, H., Peterman, J.B., Tobler, P.H., Janzer, R., Hokfelt, T., Lundberg, J.M., Cuello, C., and Fischer, J.A., 1985, Calcitonin gene-related peptide and its binding sites in the human central nervous system and pituitary, Proc. Natl. Acad. Sci., 82:248.PubMedCrossRefGoogle Scholar
  116. 116.
    Van Dijk, A., Richards, J. G., Trzeciak, A., Gillessen, D., and Mohler, H., 1984, Cholecystokinin receptors: Biochemical demonstration and autoradiographical localization in rat brain and pancreas using [3H]cholecystokinin-8 as radioligand, J. Neurosci., 4:1021.PubMedGoogle Scholar
  117. 116a.
    Vigna, S. R., Giraud, A. S., Reeve, J. R. Jr., and Walsh, J.H., 1988, Biological activity of oxidized and reduced io-Google Scholar
  118. 117.
    Vigna, S. R., Mantyh, C. R., Giraud, A. S., Soll, A. H., Walsh, J.H., and Mantyh, P.W., 1987, Localization of specific binding sites for bombesin in the canine gastrointestinal tract, Gastroenterology, 93:1287.PubMedGoogle Scholar
  119. 118.
    Wiesenfeld-Hallin, Z., Hokfelt, T., Lundberg, J. M., Forssmann, W.G., Reinecke, M., Tschopp, F.A., and Fischer, J.A., 1984, Immunoreactive calcitonin gene-related peptide and substance P coexist in sensory neurons to the spinal cord and interact in spinal behavioral responses of the rat, Neurosci. Letts., 199:2.Google Scholar
  120. 119.
    Young, W.S. III, and Kuhar, M.J., 1979, A new method for receptor autoadiography: [3H]-opioid receptors in rat brain, Brain Res., 179:255.PubMedCrossRefGoogle Scholar
  121. 120.
    Zarbin, M. A., Innis, R. B., Wamsley, J. K., Snyder, S.H., and Kuhar, M.J., 1983, Autoradiographic localization of cho-lecystokinin receptors in rodent brain, J. Neurosci., 3:877.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • P. W. Mantyh
    • 1
  • M. Catton
    • 1
  • J. E. Maggio
    • 2
  • S. R. Vigna
    • 3
  1. 1.Molecular Neurobiology Lab (151)VA Medical CenterMinneapolisUSA
  2. 2.Department of Biological Chemistry and Molecular PharmacologyHarvard Medical SchoolBostonUSA
  3. 3.Department of Cell BiologyDuke University Medical CenterDurhamUSA

Personalised recommendations