Peptides and their Receptors on Afferent Neurons to the Upper Gastrointestinal Tract

  • G. J. Dockray
  • E. R. Forster
  • S. M. Louis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 298)

Abstract

The two morphological divisions of the afferent innervation of the upper gastrointestinal tract, the vagal and splanchnic nerves, are distinguishable in functional and in neurochemical terms. It has been known since the early part of the century that the vagal pathway mediates physiological reflexes involved in the normal control of gastric motility and secretion, and that the splanchnic pathway mediates the effects of noxious stimulation of the gut (Hertz, 1911). Peptides are involved in these functions in two ways — as mediators of some of the effects of nerve stimulation, and as modulators of afferent discharge by acting at peptide receptors expressed on afferent nerve fibres (Dockray, 1988). Splanchnic afferents are a rich source of neuropeptides and provide a good illustration of how peptides might mediate the function of some visceral afferents, while vagal fibres express receptors for several peptides and so illustrate modulatory functions. The present account will deal with the physiological significance of these actions.

Keywords

Gastric Emptying Calcitonin Gene Related Peptide Vasoactive Intestinal Polypeptide Delay Gastric Emptying Afferent Innervation 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Barthó, L., Holzer, P., Lembeck, F. and Szolcsány, J., 1982, Evidence that the contractile response of the guinea-pig ileum to capsaicin is due to release of substance P, J. Physiol., 332: 157.PubMedGoogle Scholar
  2. Beglinger, C., Born, W., Hildebrand, P., Ensinck, J.W., Burkhardt, F., Fischer, J.A., and Gyr, K., 1988, Calcitonin gene-related peptides I and II and calcitonin: Distinct effects on gastric acid secretion in humans, Gastroenterology, 95: 958.PubMedGoogle Scholar
  3. Bremner, A.J., Dockray, G.J., and Forster, E.R., 1990, The mechanism of action of liquid test meals on gastric emptying in rat, J. Physiol., 422: 63P.Google Scholar
  4. Cottrell, D.F., and Iggo, A., 1984, The responses of duodenal tension receptors in sheep to pentagastrin, cholecystokinin and some other drugs, J. Physiol., 354: 477.PubMedGoogle Scholar
  5. Davison, J.S., and Clarke G.D., 1988, Mechanical properties and sensitivity to CCK of vagal gastric slowly adapting mechano-receptors, Am. J. Physiol., 255: G55.Google Scholar
  6. Debas, H.T., Farooq, O., and Grossman, M.I., 1975, Inhibition of gastric emptying is a physiological action of cholecystokinin, Gastroenterology, 68: 1211.PubMedGoogle Scholar
  7. Delbro, D., Fändriks, L., Rosel, S., and Folkers, K., 1983, Inhibition of antidromically induced stimulation of gastric motility by substance P receptor blockade, Acta Physiol. Scand., 118: 309.PubMedCrossRefGoogle Scholar
  8. Dimaline, R., Dockray, G.J., and Green, T., 1988, The role of the coeliac ganglion in the control of gastric emptying in the rat, J. Physiol., 403: 53P.Google Scholar
  9. Dockray, G.J., 1988, Regulatory peptides and the neuroendocrino-logy of gut-brain relations, Quart. J. Expl. Physiol., 73: 703.Google Scholar
  10. Dunning, B.E., and Taborsky, G.J., 1987, Calcitonin gene-related peptide: A potent and selective stimulator of gastrointestinal somatostatin secretion, Endocrinology, 120: 1774.PubMedCrossRefGoogle Scholar
  11. Evangelista, S., Lippe, I.Th., Rovero, P., Maggi, C.A., and Meli, A., 1989, Tachykinins protect against ethanol-induced gastric lesions in rats, Peptides, 79: 81.Google Scholar
  12. Fändriks, L., and Delbro, D., 1983, Neural stimulation of gastric bicarbonate secretion in the cat. An involvement of vagal axon-reflexes and substance P? Acta Physiol. Scand., 118: 301.PubMedCrossRefGoogle Scholar
  13. Flood, J.F., Smith, G.E., and Morley, J.E., 1989, Modulation of memory processing by cholecystokinin: Dependence on the vagus nerve, Science, 236: 832.CrossRefGoogle Scholar
  14. Forster, E.R., Green, T., Elliot, M., Bremner, A., and Dockray, G.J., 1990, The role of afferent neurons in the action of cholecystokinin, acid and hyperosmolal solutions on gastric emptying in the rat, Am. J. Physiol., in press.Google Scholar
  15. Forster, E.R., 1990, The role of vasoactive intestinal polypeptide in the control of gastric emptying in the rat, J. Physiol., in press.Google Scholar
  16. Freidinger, R.M., 1989, Cholecystokinin and gastrin antagonists, Med. Res. Rev., 9: 271.PubMedCrossRefGoogle Scholar
  17. Green, T., Dimaline, R., Peikin, S., and Dockray, G.J., 1988, Action of the cholecystokinin antagonist L364,718 on gastric emptying in the rat, Am. J. Physiol., 255: G685.Google Scholar
  18. Green, T., and Dockray, G.J., 1988, Characterization of the peptidergic afferent innervation of the stomach in the rat, mouse and guinea pig, Neuroscience, 25: 181.PubMedCrossRefGoogle Scholar
  19. Hamamura, T., Kazahaya, Yl, and Otsuki, S., 1989, Ceruletide suppresses endogenous dopamine release via vagal afferent system, studied by in vivo intracerebral dialysis, Brain Res., 483: 78.PubMedCrossRefGoogle Scholar
  20. Hertz, A.F., 1911, “The sensibility of the alimentary canal”, Oxford University Press.Google Scholar
  21. Hodson, C.A., Burden, H.W., and Lawrence, I.E. Jr., 1986, Intraperitoneal cholecystokinin administration inhibits prolactin release: an effect prevented by vagotomy, IRCS Medical Science, 14: 551.Google Scholar
  22. Holzer, P., and Lippe, I.Th., 1988, Stimulation of afferent nerve endings by intragastric capsaicin protects against ethanol-induced damage of gastric mucosa, Neuroscience, 27: 981.PubMedCrossRefGoogle Scholar
  23. Holzer, P., Pabst, M.A., and Lippe, I.Th., 1989, Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the rat gastric mucosa, Gastroenterology, 96: 1425.PubMedGoogle Scholar
  24. Holzer, P., and Sametz, W., 1986, Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons, Gastroenterology, 91: 975.PubMedGoogle Scholar
  25. Isenberg, J.I., and Csendes, A., 1972, Effect of octapeptide of cholecystokinin on canine pyloric pressure, Am. J. Physiol., 222: 428.PubMedGoogle Scholar
  26. Janig, W., and Morrison, J.F.B., 1986, Functional properties of spinal visceral afferents supplying abdominal and pelvic organs, with special emphasis on visceral nociception, Progress in Brain Research, 67: 87.PubMedCrossRefGoogle Scholar
  27. Kessler, J.P., and Beaudet, A., 1989, Association of neurotensin binding sites with sensory and visceromotor components of the vagus nerve, J. Neurosci., 9: 466.PubMedGoogle Scholar
  28. Kleibeuker, J.H., Beekhuis, H., Jansen, J.B.M.J., Piers, D.A., and Lamers, C.B.H.W., 1988, Cholecystokinin is a physiological hormonal mediator of fat-induced inhibition of gastric emptying in man, Eur. J. Clin. Invest., 18: 173.PubMedCrossRefGoogle Scholar
  29. Kawasaki, K., Kodama, M., and Matsushita, A., 1983, Caerulein, a cholecystokinin-related peptide, depresses somatic function via the vagal afferent system, Life Sciences, 33: 1045.PubMedCrossRefGoogle Scholar
  30. Liddle, R.A., Morita, E.T., Conrad, C.F., and Williams, J.A., 1986, Regulation of gastric emptying in humans by cholecystokinins, J. Clin. Invest., 77: 992.PubMedCrossRefGoogle Scholar
  31. Louis, S.M., Jamieson, A., Russell, N., and Dockray, G.J., 1989a, The role of substance P and CGRP in neurogenic plasma extravasation and vasodilatation in the rat, Neuroscience, 32: 581.PubMedCrossRefGoogle Scholar
  32. Louis, S.M., Johnstone, D., Russell, N.J.W., Jamieson, A., and Dockray, G.J., 1989b, Antibodies to calcitonin gene-related peptide reduce inflammation induced by topical mustard oil but not that due to carrageenin in the rat, Neurosci. Lett., 102: 257.PubMedCrossRefGoogle Scholar
  33. McCann, M.J., Verbalis, J.G., and Sticker, E.M., 1988, Capsaicin pretreatment attenuates multiple responses to cholecystokinin in rats, J. Autonomic Ner. System, 23: 265.CrossRefGoogle Scholar
  34. Maggi, C.A., Santicioli, P., Renzi, D., Patachini, R., Surrenti, G., and Meli, A., 1989, Release of substance P- and calcitonin gene-related peptide-like immunoreactivity and motor response of the isolated guinea pig gallbladder to capsaicin, Gastroenterology, 96: 1093.PubMedGoogle Scholar
  35. Meyer, B.M., Beglinger, C., Jansen, J.B.M.J., Rovati, L.C., Werth, B.A., Hildebrand, P., Zach, D., Stalder, G.A., 1989, Role of cholecystokinin in regulation of gastrointestinal motor functions, The Lancet, 1: 12.CrossRefGoogle Scholar
  36. Moran, T.H., Smith, G.P., Hostetier, A.M., and McHugh, P.R., 1987, Transport of cholecystokinin (CCK) binding sites in subdiaphragmatic vagal branches, Brain Research, 415: 149.PubMedCrossRefGoogle Scholar
  37. Morgan, K.G., Schmalz, P.F., Go, V.L.W., and Szurszewski, J.H., 1978, Electrical and mechanical effects of molecular variants of CCK on antral smooth muscle, Am. J. Physiol., 235: E324.Google Scholar
  38. Mulderry, P.K., Ghatei, M.A., Spokes, R.A., Jones, P.M., Pierson, A.M., Hamid, 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
  39. Niijima, A., 1981, Visceral afferents and metabolic function, Diabetologia 20: 325.PubMedCrossRefGoogle Scholar
  40. Niijima, A., 1983, Glucose-sensitive afferent nerve fibres in the liver and their role in food intake and blood glucose regulation, J. Aut. Nerv. System, 9: 207.CrossRefGoogle Scholar
  41. Paintal, A.S., 1953, Impulses in vagal afferent fibres from stretch receptors in the stomach and their role in the peripheral mechanism of hunger, Nature, 172: 1194.PubMedCrossRefGoogle Scholar
  42. Raybould, H.E., Roberts, M.E., and Dockray, G.J., 1987, Reflex decreases in intragastric pressure in response to cholecystokinin in rats, Am. J. Physiol., 253: G165.Google Scholar
  43. Raybould, H.E., Gayon, R., and Dockray, G.J., 1985, CNS effects of circulating CCK8 — involvement of brainstem neurones responding to gastric distension, Brain Res., 342: 187.PubMedCrossRefGoogle Scholar
  44. Raybould, H.E., Gayton, R.J., and Dockray, G.J., 1988, Mechanisms of action of peripherally administered cholecystokinin octapeptide on brain stem neurones in the rat, J. Neurosci., 8: 3018.PubMedGoogle Scholar
  45. Raybould, H.E., and Taché, Y., 1988, cholecystokinin inhibits gastric motilitiy and emptying via a capsaicin-sensitive vagal pathway in rats, Am. J. Physiol., 255: G242.Google Scholar
  46. Renzi, D., Santicioli, P., Maggi, C.A., Surrenti, C., Pradelles, P., and Meli, A., 1988, Capsaicin-induced release of substance P-like immunoreactivity from the guinea pig stomach in vitro and in vivo. Neuroscience Letters, 92: 254.PubMedCrossRefGoogle Scholar
  47. Ritter, R.C, Kalivas, P., and Bernier, S., 1986, Cholecystokinin-induced suppression of locomotion is attenuated in capsaicin pretreated rats, Peptides, 7: 587.PubMedCrossRefGoogle Scholar
  48. Schultz, H.D., Gardner, D.G., Deschepper, C.F., Coleridge, H.M., and Coleridge, J.C.G., 1988, Vagal C-fiber blockade abolishes sympathetic inhibition by atrial natriuretic factor, Am. J., Physiol., 255: R6.Google Scholar
  49. Sharkey, K.A., Williams, R.G., Dockray, G.J., 1983, Sensory substance P innervation of the stomach and pancreas: Demonstration of capsaicin-sensitive sensory neurones in the rat by combined immunohistochemistry and retrograde tracing, Gastroenterology, 87: 914.Google Scholar
  50. Smith, G.P., Jerome, C., and Norgren, R., 1985, Afferent axons in abdominal vagus mediate satiety effect of cholecystokinin in rats, Am. J. Physiol., 249: R638.Google Scholar
  51. Sternini, C., Reeve, J.R., Jr., and Brecha, N., 1987, Distribution and characterization of calcitonin gene-related peptide immunoreactivity in the digestive system of normal and capsaicin-treated rats, Gastroenterology, 93: 852.PubMedGoogle Scholar
  52. 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 the rat gut and pancreas, J. Neurosci., 7: 2674.PubMedGoogle Scholar
  53. Taché, Y., Pappas, T., Lauffenburger, M., Goto, Y., Walsh, J.H., and Debas, H., 1984, Calcitonin gene-related peptide; potent peripheral inhibitor of gastric acid secretion in rats and dogs, Gastroenterology, 87: 344.PubMedGoogle Scholar
  54. Tsunoo, A., Konishi, S., and Otsuka, M., 1982, Substance P as an excitatory transmitter of primary afferent neurons in guinea-pig sympathetic ganglia, Neuroscience, 7: 2025.PubMedCrossRefGoogle Scholar
  55. Varro, A., Green, T., Holmes, S., and Dockray, G.J., 1988, Calcitonin gene-related peptides in visceral afferent nerve fibres: quantification by radioimmunoassay and transmission of axonal transport rates, Neuroscience, 26: 927.PubMedCrossRefGoogle Scholar
  56. Yamagishi, T., and Debas, H.T., 1978, Cholecystokinin inhibits gastric emptying by acting on both proximal stomach and pylorus, Am. J. Physiol., 234: E375.Google Scholar
  57. Zarbin, M.A., Wamsley, J.K., Innis, R.B., and Kuhar, M.J., 1981, Cholecystokinin receptors; presence and axonal flow in the rat vagus nerve, Life Sciences, 29: 697..cp255PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • G. J. Dockray
    • 1
  • E. R. Forster
    • 1
  • S. M. Louis
    • 1
  1. 1.MRC Secretory Control Research Group, Physiological LaboratoryUniversity of LiverpoolLiverpoolEngland

Personalised recommendations