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Regulatory peptides in the respiratory system

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Summary

Many regulatory peptides have been described in the respiratory tract of animals and humans. Some peptides (bombesin, calcitonin, calcitonin gene-related peptide) are localised to neuroendocrine cells and may have a trophic or transmitter role. Others are localised to motor nerves. Vasoactive intestinal peptide and peptide histidine isoleucine are candidates for neurotransmitters of non-adrenergic inhibitory fibres and may be cotransmitters in cholinergic nerves. These peptides may regulate airway smooth muscle tone, bronchial blood flow and airway secretions. Sensory neuropeptides (substance P, neurokinin A and B, calcitonin gene-related peptide) may contract airway smooth muscle, stimulate mucus secretion and regulate bronchial blood flow and microvascular permeability. If released by an axon reflex mechanism these peptides may be involved in the pathogenesis of asthma. Other peptides, such as galanin and neuropeptide Y, are also present but their function is not yet known.

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Literature

  1. Andersson, P., and Persson, H., Effect of substance P on pulmonary resistance and dynamic pulmonary compliance in the anaesthetized cat and guinea-pig. Acta pharmac. toxic.41 (1977) 444–448.

    CAS  Google Scholar 

  2. Andersson, R. G. G., and Grundstrom, N., The excitatory non-cholinergic, non-adrenergic system of the guinea-pig airways. Eur. J. respir. Dis.64 (1983) 141–157.

    Google Scholar 

  3. Barnes, P. J., The third nervous system in the lung: physiology and clinical perspectives. Thorax39 (1984) 561–567.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Barnes, P. J., Non-adrenergic non-cholinergic neural control of human airways. Archs int. Pharmacodyn.280 (1986) 208–228.

    CAS  Google Scholar 

  5. Barnes, P. J., Asthma as an axon reflex. Lancet1 (1986) 242–245.

    CAS  PubMed  Google Scholar 

  6. Barnes, P. J., Neural control of human airways in health and disease. State of the art. Am. Rev. respir. Dis.134 (1986) 1289–1314.

    CAS  PubMed  Google Scholar 

  7. Barnes, P. J., Neuropeptides in the lung: localization, function and pathophysiological implications. J. allergy clin. Immun.79 (1987) 285–295.

    CAS  PubMed  Google Scholar 

  8. Barnes, P. J., Airway neuropeptides and asthma. Trends pharm. Sci.8 (1987) 24–27.

    CAS  Google Scholar 

  9. Barnes, P. J., Vasoactive intestinal peptide and pulmonary function, in: Current Topics in Pulmonary Pharmacology and Toxicology. Ed. M. A. Hollinger, Preager Scientific, Philadelphia 1987, in press.

    Google Scholar 

  10. Barnes, P. J., Bloom, S. R., and Dixon, C. M. S., VIP and asthma. Lancet1 (1984) 112.

    CAS  PubMed  Google Scholar 

  11. Barnes, P. J., Brown, M. J., Dollery, C. T., Fuller, R. W., Heavey, D. J., and Ind, P. W., Histamine is released from skin by substance P but does act as the final vasodilator in the axon reflex. Br. J. Pharmac.88 (1986) 741–745.

    CAS  Google Scholar 

  12. Barnes, P. J., Cadieux, A., Carstairs, J. R., Greenberg, B., Polak, J. M., and Rhoden, K., Vasoactive intestinal peptide in bovine pulmonary artery: localisation, function and receptor autoradiography. Br. J. Pharmac.89 (1986) 157–162.

    CAS  Google Scholar 

  13. Barnes, P. J., Conradson, T.-B., Dixon, C. M. S., and Fuller, R. W., A comparison of the cutaneous actions of substance P, neurokinin A and calcitonin gene-related peptide in man. J. Physiol.374 (1986) 22P.

    Google Scholar 

  14. Barnes, P. J., Crossman, D. C., and Fuller R. W., Cutaneous effects of neuropeptides are dependent upon both histamine and cyclooxygenase products. Br. J. Pharmac.90 (1987).

  15. Barnes, P. J., Dewar, A., and Rogers, D. F., Human bronchial secretion: effect of substance P, muscarinic and adrenergic stimulation in vitro. Br. J. Pharmac.89 (1986) 767P.

    Google Scholar 

  16. Barnes, P. J., and Dixon, C. M. S., The effect of inhaled vasoactive intestinal peptide on bronchial hyperreactivity in man. Am. Rev. respir. Dis.130 (1984) 162–166.

    CAS  PubMed  Google Scholar 

  17. Borson, D. B., Charlin, M., Gold, B. D., and Nadel, J. A., Neural regulation of 35 SO4-macromolecule secretion from tracheal glands of ferrets. J. appl. Physiol.57 (1984) 457–466.

    CAS  PubMed  Google Scholar 

  18. Brain, S. D., Williams, T. J., Tippins, J. R., Morris, H. R., and MacIntyre, I., Calcitonin gene-related peptide is a potent vasodilator. Nature313 (1985) 54–56.

    CAS  PubMed  Google Scholar 

  19. Bungaard, A., Enehjelm, S. D., and Aggestrop, S., Pretreatment of exercise-induced asthma with inhaled vasoactive intestinal peptide (VIP). Eur. J. respir. Dis.64 (1983) 427–429.

    Google Scholar 

  20. Cameron, A. R., Johnston, C. D., Kirkpatrick, C. T., and Kirkpatrick, M. C. A., The quest for the inhibitory neurotransmitter in bovine tracheal smooth muscle. Q. J. exp. Psychol.68 (1983) 413–426.

    CAS  Google Scholar 

  21. Carstairs, J. R., and Barnes, P. J., Visualization of vasoactive intestinal peptide receptors in human and guinea pig lung. J. Pharmac. exp. Ther.239 (1986) 249–255.

    CAS  Google Scholar 

  22. Carstairs, J. R., and Barnes, P. J., Autoradiographic mapping of substance P receptors in lung. Eur. J. Pharmac.127 (1986) 295–296.

    Google Scholar 

  23. Cheung, A., Polak, J. M., Bauer, F. E., Christofides, N. D., Cadieux, A., Springall, D. R., and Bloom, S. R., The distribution of galanin immunoreactivity in the respiratory tract of pig, guinea pig, rat and dog. Thorax40 (1985) 889–896.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Christofides, N. D., Yiangou, Y., Piper, P. J., Ghatei, M. A., Sheppard, M. N., Tatemoto, K., Polak, J. M., and Bloom, S. R., Distribution of peptide histidine isoleucine in the mammalian respiratory tract and some aspects of its pharmacology. Endocrinology115 (1984) 1958–1963.

    CAS  PubMed  Google Scholar 

  25. Coles, S. J., Neill, K. H., and Reid, L. M., Potent stimulation of glycoprotein secretion in canine trachea by substance P. J. appl. Physiol.57 (1984) 1323–1327.

    CAS  PubMed  Google Scholar 

  26. Coles, S. J., Said, S. I., and Reid, L. M., Inhibition by vasoactive intestinal peptide of glycoconjugate and lysozyme secretion by human airways in vitro. Am. Rev. respir. Dis.124 (1981) 531–536.

    CAS  PubMed  Google Scholar 

  27. Cutz, E., Neuroendocrine cells of the lung — an overview of morphologic characteristics and development. Exp. Lung Res.3 (1982) 185–208.

    CAS  PubMed  Google Scholar 

  28. Dey, R. D., Shannon, W. A., and Said, S. I., Localization of VIP-immunoreactive nerves in airways and pulmonary vessels of dogs, cats and human subjects. Cell Tissue Res.220 (1981) 231–238.

    CAS  PubMed  Google Scholar 

  29. Diamond, L., and O'Donnell, M., A non-adrenergic vagal inhibitory pathway to feline airways. Science208 (1980) 185–188.

    CAS  PubMed  Google Scholar 

  30. Diamond, L., Szareck, J. L., Gillespie, M. N., and Altiere, R. J., In vivo bronchodilator activity of vasoactive intestinal peptide in the cat. Am. Rev. respir. Dis.128 (1983) 827–832.

    CAS  PubMed  Google Scholar 

  31. Ekblad, E., Hakanson, R., Sundler, F., and Wahlestedt, C., Galanin: neuromodulatory and direct contractile effects on smooth muscle preparations. Br. J. Pharmac.86 (1985) 241–246.

    CAS  Google Scholar 

  32. Foreman, J. C., Jordan, C. C., Oehme, P., and Renner, H., Structureactivity relationships for some substance P-related peptides that cause wheal and flare reactions in human skin. J. Physiol.335 (1983) 449–465.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Fuller, R. W., Dixon, C. M. S., and Barnes, P. J., The bronchoconstrictor response to inhaled capsaicin in humans. J. appl. Physiol.85 (1985) 1080–1084.

    Google Scholar 

  34. Fuller, R. W., Dixon, C. M. S., Cuss, F. M. C., and Barnes, P. J., Bradykinin-induced bronchoconstriction in man: mode of action. Am. Rev. respir. Dis.135 (1986) 176–180.

    Google Scholar 

  35. Fuller, R. W., Maxwell, D. L., Dixon, C. M. S., McGregor, G. P., Barnes, V. F., Bloom, S. R., and Barnes, P. J., The effects of substance P on cardiovascular and respiratory function in human subjects. J. appl. Physiol. (1987) in press.

  36. Ghatei, M. A., Sheppard, M., O'Shaunessy, D. J., Adrian, T. E., MacGregor, J. M., Polak, J. M., and Bloom, S. R., Regulatory peptides in the mammalian respiratory tract. Endocrinology111 (1982) 1248–1254.

    CAS  PubMed  Google Scholar 

  37. Ghatei, M. A., Sheppard, M. N., Henzen-Logman, S., Blank, M. A., Polak, J. M., and Bloom, S. R., Bombesin and vasoactive intestinal polypeptide in the developing lung: marked changes in acute respiratory distress syndrome. J. clin. Endocr.57 (1983) 1226–1232.

    CAS  PubMed  Google Scholar 

  38. Greenberg, B., Rhoden, K., and Barnes, P. J., Vasoactive intestinal peptide causes non-endothelial dependent relaxation in human and bovine pulmonary arteries. Blood Vessels24 (1987) 45–50.

    CAS  PubMed  Google Scholar 

  39. Impicciatore, M., and Bertaccini, G., The bronchoconstrictor action of the tetradeaupepdite bombesin in the guinea pig. J. Pharm. Pharmac.25 (1973) 812–815.

    Google Scholar 

  40. Irvin, C. G., Martin, R. R., and Macklem,P. T., Non purinergic nature and efficacy of non adrenergic bronchodilatation. J. appl. Physiol.52 (1982) 562–569.

    CAS  PubMed  Google Scholar 

  41. Ito, Y., and Takeda, K., Non-adrenergic inhibitory nerves and putative transmitters in the smooth muscle of cat trachea. J. Physiol.330 (1982) 497–511.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Karlsson, J.-A., Finney, M. J. B., Persson, C. G. A., and Post C., Substance P antagonist and the role of tachykinins in non-cholinergic bronchoconstriction. Life Sci.35 (1984) 2681–2691.

    CAS  PubMed  Google Scholar 

  43. Karlsson, J.-A., and Persson, C. G. A., Neither vasoactive intestinal peptide (VIP) nor purine derivatives may mediate non-adrenergic tracheal inhibition. Acta Physiol. scand.122 (1984) 589–598.

    CAS  PubMed  Google Scholar 

  44. Laitinen, L. A., Heino, M., Laitinen, A., Kava, T., and Haahtela, T., Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am. Rev. respir. Dis.131 (1985) 599–606.

    CAS  PubMed  Google Scholar 

  45. Laitinen, L. A., Laitinen, A., Panula, P. A., Partanen, M., Tervo, K., and Tervo T., Immunohistochemical demonstration of substance P in the lower respiratory tract of the rabbit and not of man. Thorax38 (1983) 531–536.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Laitinen, L. A., Laitinen, A., and Widdicombe, J. G., Effects of inflammatory and other mediators on airway vascular beds. Am. Rev. respir. Dis. (1987) in press.

  47. Laitinen, A., Partanen, M., Heruonen, A., Peto-Huikko, M., and Laitinen, L. A., VIP-like immunoreactive nerves in human respiratory tract. Light and electron microscopic study. Histochemistry82 (1985) 313–319.

    CAS  PubMed  Google Scholar 

  48. Lauweryns, J. M., van Lomme, L. A. T., and Dom, R. J., Innervation of rabbit intrapulmonary neuroepithelial bodies. Quantitative ultrastructural study after vagotomy. J. neurol. Sci.67 (1985) 81–92.

    CAS  PubMed  Google Scholar 

  49. Lazarus, S. C., Basbaum, C. B., Barnes, P. J., and Gold, W. M., cAMP immunocytochemistry provides evidence for functional VIP receptors in trachea. Am. J. Physiol.251 (1986) C115–119.

    CAS  PubMed  Google Scholar 

  50. Lee, C.-M., Campbell, N. J., Williams, B. J., and Iversen, L. L., Multiple tachykinin binding sites in peripheral tissues and in brain. Eur. J. Pharmac.130 (1986) 209–217.

    CAS  Google Scholar 

  51. Leroux, P., Vaudry, H., Fournier, A., St Pierre, S., and Pelletier, G., Characterization and localization of vasoactive intetinal peptide receptors in the rat lung. Endocrinology114 (1984) 1506–1512.

    CAS  PubMed  Google Scholar 

  52. Lundberg, J. M., Evidence for coexistenceof vasoactive intestinal peptide (VIP) and acetylcholine in neurons of cat exocrine glands: morphological, biochemical and functional studies. Acta physiol. scand.496 (1981) 1–57.

    CAS  Google Scholar 

  53. Lundberg, J. M., Anders, F.-C., Hua, X., Hökfelt, T., and Fischer, J. A., Coexistence of substance P and calcitonin gene-related peptidelike immunoreactivities in sensory nerves in relation to cardiovascular and bronchoconstrictor effects of capsaicin. Eur. J. Pharmac.108 (1985) 315–319.

    CAS  Google Scholar 

  54. Lundberg, J. M., Brodin, E., and Saria, A., Effects and distribution of vagal capsaicin-sensitive substance P neurons with specialreference to the trachea and lungs. Acta physiol. scand.119 (1983) 243–252.

    CAS  PubMed  Google Scholar 

  55. Lundberg, J. M., Fahrenkrug, J., Hökfelt, T., Martling, C. R., Larsson, O., Tatemoto, K., and Anggard, A., Coexistence of peptide H1 (PH1) and VIP in nerves regulating blood flow and bronchial smooth muscle tone in various including man. Peptides5 (1984) 593–606.

    CAS  PubMed  Google Scholar 

  56. Lundberg, J. M., Hökfelt, T., Martling, C.-R., Saria, A., and Cuello, C., Substance P-immunoreactive sensory nerves in the lower respiratory tract of various mammals including man. Cell Tissue Res.235 (1984) 251–261.

    CAS  PubMed  Google Scholar 

  57. Lundberg, J. M., Martling, C.-R., and Saria, A., Substance P and capsaicin-induced contraction of human bronchi. Acta physiol. scand.119 (1983) 49–53.

    CAS  PubMed  Google Scholar 

  58. Lundberg, J. M., and Saria, A., Capsaicin-induced desensitization of the airway mucosa to cigarette smoke, mechanical and chemical irritants. Nature302 (1983) 251–253.

    CAS  PubMed  Google Scholar 

  59. Lundberg, J. M., Terenius, L., Hökfelt, T., Martling, C. R., Tatemoto, K., Mutt, V., Polak, J., Bloom, S., and Goldstein, M., Neuropeptide Y (NPY)-like immunoreactivity in peripheral nonadrenergic neurons and effects of NPY on sympathetic function. Acta physiol. scand.116 (1982) 477–480.

    CAS  PubMed  Google Scholar 

  60. Matsuzaki, Y., Hamasaki, Y., and Said, S. I., Vasoactive in testinal peptide: a possible transmitter of nonadrenergic relaxation of guinea pig airways. Science210 (1980) 1252–1253.

    CAS  PubMed  Google Scholar 

  61. Michoud, M.-C., Amyot, R., and Jeanneret-Grosjean, A., Bronchodilatation induced by laryngeal stiumulation in humans. Am. Rev. respir. Dis.131 (1985) A 284.

    Google Scholar 

  62. Morice, A., Unwin, R. J., and Sever P. S., Vasoactive intestinal peptide causes bronchodilatation and protects against histamine-induced bronchoconstriction in asthmatic subjects. Lancet2 (1983) 1225–1226.

    CAS  PubMed  Google Scholar 

  63. Nadel, J. A., and Barnes, P. J., Autonomic regulation of the airways. A. Rev. Med.35 (1984) 451–467.

    CAS  Google Scholar 

  64. Nathanson, I., Widdcombe, J. H., and Barnes, P. J., Effect of vasoactive intestinal peptide on ion transport across dog traceeal epitheilum. J. appl. Physiol.55 (1983) 1844–1848.

    CAS  PubMed  Google Scholar 

  65. Nawa, H., Hirose, T., Takashima, H., Inayama, S., and Nakanishi, S., Nucleotide sequences of cloned cDNAs for two types of bovine brain substance P precursor. Nature306 (1983) 32–36.

    CAS  PubMed  Google Scholar 

  66. Pack, R. J., and Widdicombe, J. G., Amine containing cells of the lung. Eur. J. respir. Dis.65 (1984) 559–578).

    CAS  PubMed  Google Scholar 

  67. Palmer, J. B., Cuss, F. M. C., and Barnes, P. J., VIP and PHM and their role in non-adrenergic inhibitory responses in isolated human airways. J. appl. Physiol.61 (1986) 1322–1328.

    CAS  PubMed  Google Scholar 

  68. Palmer, J. B., Cuss, F. M. C., and Barnes, P. J., Sensory neuropeptides and human airway function. Am. Rev. respir. Dis.133 (1986) A239.

    Google Scholar 

  69. Palmer, J. B. D., Cuss, F. M. C., Ghatei, M. A., Springall, D. R., Cadieux, A., Bloom, S. R., Polak, J. M., and Barnes, P. J., Calcitonin gene-related peptide is localised to human airway nerves and potently constricts human airway smooth muscle. Thorax40 (1985) 713.

    Google Scholar 

  70. Palmer, J. B. D., Cuss, F. M. C., Warren, J. B., and Barnes, P. J., The effect of infused vasoactive intestinal peptide on airway function in normal subjects. Thorax41 (1986) 663–666.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Palmer, J. B., Sampson, A. P., and Barnes, P. J., Cholinergic and non-adrenergic inhibitory responses in bovine airways: distribution and functional association. Am. Rev. respir. Dis.131 (1985) A282.

    Google Scholar 

  72. Partanen, M., Laitinen, A., Pelto-Huikko, M., Laitinen, L. A., and Hervonen, A., Electronmicroscopic study on granule containing (APUD) cells in adult human lung. Cell Tissue Res. (1986) in press.

  73. Payan, G. P., Levine, J. D., and Goetzl, E. J., Modulation of immunity and hypersensitivity by sensory neuropeptides. J. Immun.132 (1984) 1601–1604.

    CAS  PubMed  Google Scholar 

  74. Peatfield, A. C., Barnes, P. J., Bratcher, C., Nadel, J. A., and Davis, B., Vasoactive intestinal peptide stimulates tracheal submucosal gland secretion in ferret. Am. Rev. respir. Dis.128 (1983) 89–93.

    CAS  PubMed  Google Scholar 

  75. Peatfield, A. C., and Richarson, P. S., Evidence for non-cholinergic, non-adrenergic nervous control of mucus secretion into the cat trachea. J. Physiol.342 (1983) 335–345.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Polak, J. M., and Bloom, S. R., Regulatory peptides of the gastrointestinal and respiratory tracts. Archs int. Pharmacodyn.280, Suppl. (1986) 16–49.

    CAS  Google Scholar 

  77. Richardson, J. B., Nonadrenergic inhibitory innervation of the lung. Lung159 (1981) 315–322.

    CAS  PubMed  Google Scholar 

  78. Robberecht, P., Chatelain, P., De Neef, P., Camus, J.-C., Waelbroeck, M., and Christophe, J., Presence of vasoactive intestinal peptide receptors coupled to adenylate cyclase in rat lung membranes. Biochem. biophys. Acta678 (1981) 76–82.

    CAS  PubMed  Google Scholar 

  79. Said, S. I., Vasoactive peptides in the lung, with special reference to vasoactive intestinal peptide. Exp. Lung Res.3 (1982) 343–348.

    CAS  PubMed  Google Scholar 

  80. Sheppard, M. N., Polak, J. M., Allen, J. M., and Bloom, S. R., Neuropeptide tyrosine (NYP): a newly discovered peptide is present in the mammalian respiratory tract. Thorax39 (1984) 326–330.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Szarek, J. L., Gillespie, M. N., Altiere, R. J., and Diamond, L., Mechanical irritation of the larynx reflexing evokes non-adrenergic bronchodilatation. Am. Rev. respir. Dis.129 (1984) 243.

    Google Scholar 

  82. Tanaka, D. T., and Grunstein, M. M., Mechanisms of substance P-induced contraction of rabbit airway smooth muscle. J. appl. Physiol.57 (1984) 1551–1557.

    CAS  PubMed  Google Scholar 

  83. Theodorsson-Nerheim, E., Hua, X., Brodin, E., and Lundberg, J. M., Capsaicin treatment decreases tissue levels of neurokinin-A-like immunoreactivity in the guinea pig. Acta physiol. scand.124 (1985) 129–131.

    Google Scholar 

  84. Uddman, R., Moghimzadeh, E., and Sundler, F., Occurrence and distribution of GRP-immunoreactive nerve fibres in the respiratory tract. Archs Otolar.239 (1984) 145–151.

    CAS  Google Scholar 

  85. Uddman, R., and Sundler, F., Vasoactive intetinal polypeptide nerves in human upper respiratory tract. Oto-rhino-lar.41 (1979) 221–226.

    CAS  Google Scholar 

  86. Undem, B. J., Dick, E. C., and Buckner, C. K., Inhibition by vasoactive intestinal peptide of antigen-induced histamine release from guinea-pig minced lung. Eur. J. Pharmac.88 (1983) 247–250.

    CAS  Google Scholar 

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  1. Department of Clinical Pharmacology, Cardiothoracic Institute, Brompton Hospital, SW3, London, England

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Barnes, P.J. Regulatory peptides in the respiratory system. Experientia 43, 832–839 (1987). https://doi.org/10.1007/BF01945361

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