Afferent Nerve-Mediated Control of Gastric Mucosal Blood Flow and Protection

  • Peter Holzer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 298)


The gastric mucosa is constantly exposed to chemical hazard, the threats being of both endogenous and exogenous origin. Most tissues would rapidly disintegrate if exposed to the concentrations of hydrochloric acid that bathe but do not harm the gastric surface epithelium. This is because a multitude of mechanisms constituting the gastric mucosal barrier (Davenport, 1972) prevent hydrogen ions from entering the tissues in quantities that would produce cell injury. Yet even a weakening of the barrier will usually not lead to any major lesion formation because emergency or protective mechanisms will take effect, limit the damage and promote repair of the injured tissue.


Gastric Mucosa Sensory Neuron Mucosal Blood Flow Gastric Mucosal Damage Sensory Nerve Ending 
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.


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  1. Barthó, L., Holzer, P., 1985, Search for a physiological role of substance P in gastrointestinal motility, Neuroscience 16:1.PubMedCrossRefGoogle Scholar
  2. Bauerfeind, P., Hof, R., Hof, A., Cucala, M., Siegrist, S., von Ritter, Ch., Fischer J.A., Blum, A.L., 1989, Effects of hCGRP I and II on gastric blood flow and acid secretion in anesthetized rabbits, Am. J. Physiol., 256:G145.Google Scholar
  3. Bevan, S., Yeats, J.C., 1989, Protons activate a sustained inward current in a subpopulation of rat isolated dorsal root ganglion (DRG) neurones, J. Physiol. (London), 417:81P.Google Scholar
  4. Bruggeman, T.M., Wood, J.G., Davenport, H.W., 1979, Local control of blood flow in the dog’s stomach: vasodilatation caused by acid back-diffusion following topical application of salicylic acid, Gastroenterology, 77:736.PubMedGoogle Scholar
  5. Cervero, F., McRitchie, H.A., 1982, Neonatal capsaicin does not affect unmyelinated efferent fibers of the autonomic nervous system: functional evidence, Brain Res., 239:283.PubMedCrossRefGoogle Scholar
  6. Cheung, L.Y., Moody, F.G., Reese, R.S., 1975, Effect of aspirin, bile salt and ethanol on canine gastric mucosal blood flow, Surgery, 77:786.PubMedGoogle Scholar
  7. Clarke, G.D., Davison, J.S., 1978, Mucosal receptors in the gastric antrum and small intestine of the rat with afferent fibres in the cervical vagus, J. Physiol. (London), 284:55.Google Scholar
  8. Davenport, H.W., 1972, The gastric mucosal barrier, Digestion, 5:162.PubMedCrossRefGoogle Scholar
  9. Dugani, A.M, Glavin, G.B., 1986, Capsaicin effects on stress pathology and gastric acid secretion in rats, Life Sci., 39:1531.PubMedCrossRefGoogle Scholar
  10. Esplugues, J.V., Whittle, B.J.R., 1990, Morphine potentiation of ethanol-induced gastric mucosal damage in the rat. Role of local sensory afferent neurons, Gastroenterology, 98:82.PubMedGoogle Scholar
  11. Esplugues, J.V., Whittle, B.J.R., Moncada S., 1989, Local opioid-sensitive afferent sensory neurones in the modulation of gastric damage induced by Paf, Br. J. Pharmacol., 97:579.PubMedCrossRefGoogle Scholar
  12. Evangelista, S., Lippe, I.T., Rovero, P., Maggi, CA., Meli, A., 1989, Tachykinins protect against ethanol-induced gastric lesions in rats, Peptides, 10:79.PubMedCrossRefGoogle Scholar
  13. Evangelista, S., Maggi, C.A., Giuliani, S., Meli, A., 1988a, Further studies on the role of the adrenals in the capsaicin-sensitive “gastric defence mechanism”, Int. J. Tiss. React., 10:253.Google Scholar
  14. Evangelista, S., Maggi, C.A., Meli, A., 1986, Evidence for a role of adrenals in the capsaicin-sensitive “gastric defence mechanism” in rats, Proc. Soc. Exp. Biol. Med., 182:568.PubMedGoogle Scholar
  15. Evangelista, S., Maggi, C.A., Meli, A., 1987, Influence of peripherally-administered peptides on ethanol-induced gastric ulcers in the rat, Gen. Pharmacol., 18:647.PubMedCrossRefGoogle Scholar
  16. Evangelista, S., Maggi, C.A., Meli, A., 1988b, Lack of influence of capsaicin-sensitive sensory fibers on adaptive cytoprotection in rat stomach, Digest Dis. Sci., 33:1050.PubMedCrossRefGoogle Scholar
  17. Fink, T., Weihe, E., 1988, Multiple neuropeptides in nerves supplying mammalian lymph nodes: messenger candidates for sensory and autonomic neuroimmunomodulation? Neurosci. Lett., 90:39.PubMedCrossRefGoogle Scholar
  18. Furness, J.B., Papka, R.E., Delia N.G., Costa, M., Eskay, R.L., 1982, Substance P-like immunoreactivity in nerves associated with the vascular system of guinea-pigs, Neuroscience, 7:447.PubMedCrossRefGoogle Scholar
  19. Gannon, B., Browning, J., O’Brien, P., 1982, The microvascular architecture of the glandular mucosa of rat stomach, J. Anat., 135:667.PubMedGoogle Scholar
  20. Gray, J.L., Bunnett, N.W., Mulvihill, S.J., Debas, H.T., 1989, Capsaicin stimulates release of calcitonin gene-related peptide (CGRP) from the isolated perfused rat stomach, Gastroenterology, 96: A181.Google Scholar
  21. Green, T., 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
  22. Guth, P.H., Leung, F.W., 1987, Physiology of the gastric circulation, in: “Physiology of the Gastrointestinal Tract”, L.R. Johnson, ed., Raven Press, New York.Google Scholar
  23. Holzer, P., 1988, Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides, Neuroscience, 24:739.PubMedCrossRefGoogle Scholar
  24. Holzer, P., Lippe, I.T., 1988, Stimulation of afferent nerve endings by intragastric capsaicin protects against ethanol-induced damage of gastric mucosa, Neuroscience, 27:981.PubMedCrossRefGoogle Scholar
  25. Holzer, P., Livingston, E.H. Guth, P.H., 1990A, Sensory neurons signal for an increase in rat gastric mucosal blood flow in the face of pending acid injury, Gastroenterology, submitted.Google Scholar
  26. Holzer, P., Pabst, M.A., Lippe, I.T., 1989, Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the rat gastric mucosa, Gastroenterology, 96:1425.PubMedGoogle Scholar
  27. Holzer, P., Pabst, M.A., Lippe, I.T., Peskar, B.M., Peskar, B.A., Livingston, E.H., Guth, P.H., 1990b, Afferent nerve-mediated protection against deep mucosal damage in the rat stomach, Gastroenterology, in press.Google Scholar
  28. Holzer, P., Peskar, B.M., Peskar, B.A., Amann, R., 1990c, Release of calcitonin gene-related peptide induced by capsaicin in the vascularly perfused rat stomach, Neurosci. Lett., 108:195.PubMedCrossRefGoogle Scholar
  29. Holzer, P., Sametz, W., 1986, Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons, Gastroenterology, 91:975.PubMedGoogle Scholar
  30. Lippe, I.T., Lorbach, M., Holzer, P., 1989a, Close arterial infusion of calcitonin gene-related peptide into the rat stomach inhibits aspirin- and ethanol-induced hemorrhagic damage, Regul. Pept., 26:35.PubMedCrossRefGoogle Scholar
  31. Lippe, I.T., Pabst, M.A., Holzer, P., 1989b, Intragastric capsaicin enhances rat gastric acid elimination and mucosal blood flow by afferent nerve stimulation, Br. J. Pharmacol., 96:91.PubMedCrossRefGoogle Scholar
  32. Maggi, C.A., Meli, A., 1988, The sensory-efferent function of capsaicin-sensitive sensory neurons, Gen. Pharmacol., 19:1.PubMedCrossRefGoogle Scholar
  33. Martling, C.-R., Lundberg, J.M., 1988, Capsaicin-sensitive afferents contribute to the acute airway edema following tracheal instillation of hydrochloric acid or gastric juice in the rat, Anesthesiology, 68:350.PubMedCrossRefGoogle Scholar
  34. Miller, T.A., Smith, G.S., Stanislawska, M., Phan, T.M., Henagan, J.M., 1989, Role of vagal innervation in adaptive cytoprotection, Digest Dis. Sci., 34:1318.Google Scholar
  35. Payan, D.G., Levine, J.D., Goetzl, E.J., 1984, Modulation of immunity and hypersensitivity by sensory neuropeptides, J. Immunol., 132:1601.PubMedGoogle Scholar
  36. Pihan, G., Majzoubi, D., Haudenschild, C., Trier, J.S., Szabo, S., 1986, Early microcirculatory stasis in acute gastric mucosal injury in the rat and prevention by 16,16-dimethyl prostaglandin E2 or sodium thiosulfate, Gastroenterology, 91:1415.PubMedGoogle Scholar
  37. Popper, P., Mantyh, C.R., Vigna, S.R., Maggio J.E., 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
  38. Renzi, D., Santicioli, P., Maggi, C.A., Surrenti, C., Pradelles, P., Meli, A., 1988, Capsaicin-induced release of substance P-like immunoreactivity from the guinea pig stomach in vitro and in vivo, Neurosci. Lett., 92:257.CrossRefGoogle Scholar
  39. Ritchie, W.P., 1975, Acute gastric mucosal damage induced by bile salts, acid and ischemia, Gastroenterology, 68:699.PubMedGoogle Scholar
  40. Rózsa, Z., Jacobson, E.D., 1989, Capsaicin-sensitive nerves are involved in bile-oleate induced intestinal hyperemia, Am. J. Physiol., 256:G476.Google Scholar
  41. Rózsa, Z., Mattila, J., Jacobson, E.D., 1988, Substance P mediates a gastrointestinal thermoreflex in rats, Gastroenterology, 95:265.PubMedGoogle Scholar
  42. Sharkey, K.A., Williams, R.G., Dockray, G.J., 1984, Sensory substance P innervation of the stomach and pancreas. Demonstration of capsaicin-sensitive sensory neurons in the rat by combined immunohistochemistry and retrograde tracing, Gastroenterology, 87:914.PubMedGoogle Scholar
  43. Silen, W., 1987, Gastric mucosal defense and repair, in: “Physiology of the Gastrointestinal Tract”, L.R. Johnson, ed., Raven Press, New York.Google Scholar
  44. Starlinger, M., Schiessel, R., Hung, C.R., Silen, W., 1981, H+ back diffusion stimulating gastric mucosal blood flow in the rabbit fundus, Surgery, 89:232.PubMedGoogle Scholar
  45. Stead, R.M., Bienenstock, J., Stanisz, A.M., 1987, Neuropeptide regulation of mucosal immunity, Immunol. Rev., 100:333.PubMedCrossRefGoogle Scholar
  46. Sternini, C., Reeve, J.R., Brecha, N., 1987, Distribution and characterization of calcitonin gene-related peptide immunoreactivity in the digestive system of normal and capsaicintreated rats, Gastroenterology, 93:852.PubMedGoogle Scholar
  47. Szolcsányi, J., 1984, Capsaicin-sensitive chemoceptive neural system with dual sensory-efferent function, in: “Antidromic Vasodilatation and Neurogenic Inflammation”, L.A. Chahl, J. Szolcsányi, F. Lembeck, eds., Akadémiai Kiadó, Budapest.Google Scholar
  48. Szolcsányi, J., Barthó, L., 1981, Impaired defense mechanism to peptic ulcer in the capsaicin-desensitized rat, in: “Gastrointestinal Defense Mechanisms”, G. Mózsik, O. Hänninen, T. Jávor, eds., Pergamon Press and Akadémiai Kiadó, Oxford and Budapest.Google Scholar
  49. Thiefin, G., Raybould, H.E., Leung, F.W., Taché, Y., Guth, P.H., 1989, Role of capsaicin-sensitive vagal afferent fibers in increased gastric mucosal blood flow induced by electrical vagal stimulation in the rat. Gastroenterology, 96:A509.Google Scholar
  50. Whittle, B.J.R., 1977, Mechanism underlying gastric mucosal damage induced by indomethacin and bile salts, and the actions of prostaglandins, Br. J. Pharmacol., 60:455.PubMedCrossRefGoogle Scholar
  51. Whittle, B.J.R., Esplugues, J.V., 1989, Gastric mucosal damage induced by an intravascular thromboxane mimetic is potentiated by the neurotoxin tetrodotoxin and capsaicin treatment, Gastroenterology, 96: A544.Google Scholar
  52. Yonei, Y., Holzer, P., Guth, P.H., 1990, Laparotomy-induced gastric protection against ethanol injury is mediated by capsaicin-sensitive sensory neurons, Gastroenterology, in press.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Peter Holzer
    • 1
    • 2
  1. 1.Center for Ulcer Research and Education, Veterans Administration Wadsworth Medical CenterUniversity of California at Los AngelesLos AngelesUSA
  2. 2.Department of Experimental and Clinical PharmacologyUniversity of GrazGrazAustria

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