Vagal Afferent Innervation and Regulation of Gastric Function

  • Helen E. Raybould
  • Peter Holzer
  • Gerard Thiefin
  • Helge H. Holzer
  • Masashi Yoneda
  • Yvette F. Tache
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 298)


It has been recognized since the beginning of the century that many gastric functions are independent of the extrinsic nervous innervation but can be modulated through these nerves by mechanisms involving afferent fibers. The visceral afferent innervation may regulate gastric function in at least two ways: first, by initiating reflexes mediated through the CNS, vago-vagal reflexes and secondly, producing changes in function through local effector mechanisms. In the following article, experimental evidence will be presented to suggest that vagal afferents regulate several gastric functions, including the gastric phase of acid secretion and mucosal blood flow, the central modulation of vago-vagal reflexes and postprandial gastric motor function.


Gastric Emptying Gastric Acid Secretion Gastric Distension Gastric Mucosal Blood Flow Capsaicin Treatment 
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. Ainsworth, A., Hall, P., Wall, P.D., Allt, G., MacKenzie, M.L., Gibson, S., and Polak, J.M., 1981, Effects of capsaicin applied locally to adult peripheral nerve. II. Anatomy and enzyme and peptide chemistry of peripheral nerve and spinal cord, Pain, 11:379.PubMedCrossRefGoogle Scholar
  2. Alfoldi, P., Obal, F., Toth, E., and Hideg, J., 1986, Capsaicin pretreatment reduces the gastric acid secretion elicited by histamine but does not affect the responses to carbachol and pentagastrin, Europ. J. Pharmacol., 123:321.CrossRefGoogle Scholar
  3. Azpiroz, F., and Malagelada, J.R., 1986, Vagally mediated gastric relaxation induced by intestinal nutrients in the dog, Am. J. Physiol., 215:G727.Google Scholar
  4. Bauerfeind, P., Hof, R., Hof, A., Cucula, M., Siegrist, S., von Ritter, C.H., Fischer, J.A., and 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
  5. Buck, S.H., and Burks, T.F., 1986, The neuropharmacology of capsaicin: a review of some recent observations, Pharmacol. Rev., 38:179.PubMedGoogle Scholar
  6. Cottrell, D.F., and Iggo, A., 1986, The responses of duodenal tension receptors in sheep to pentagastrin, cholecystokinin and some other drugs, J. Physiol., 354:477.Google Scholar
  7. Davison, J.S., and Clarke, G.D., 1988, Mechanical properties and sensitivity to CCK of vagal gastric slowly adapting mechano-receptor, Am. J. Physiol., 255:G55.Google Scholar
  8. Debas, H.T., 1987, Peripheral regulation of gastric acid secretion, in: “Physiology of the Gastrointestinal Tract,” L.R. Johnson, ed., Raven Press, New York.Google Scholar
  9. Debas, H.T., Konturek, S.J., Walsh, J.H., and Grossman, M.I., 1974, Proof of a pyloro-oxyntic reflex for stimulation of acid secretion, Gastroenterology, 66:526.PubMedGoogle Scholar
  10. 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
  11. De Ponti, F., Azpiroz, F., Malagelada, H.R., 1987, Reflex gastric relaxation in response to distension of the duodenum, Am. J. Physiol., 252:G595.Google Scholar
  12. Dinn, T.T., and Ritter, S., 1985, Capsaicin induces neuronal degeneration in the brain and spinal cord of adult rats, Soc. Neurosci., 11:349.Google Scholar
  13. Evangelista, S., Santicioli, P., Maggi, C.A., and Meli, A., 1989, Increase in gastric secretion induced by 2-deoxy-D-glucose is impaired in capsaicin pretreated rats, Brit. J. Pharmacol., 98:35.CrossRefGoogle Scholar
  14. Feldmen, M., Dickerson, R.M., McClelland, R.N., Cooper, K.A., Walsh, J.H., and Richardson, C.T., 1979, Effect of selective proximal vagotomy on food-stimulated gastric acid secretion and gastrin release in patients with duodenal ulcer, Gastroenterology, 76:926.Google Scholar
  15. Fried, M., Lochner, C., Erlacher, U., Beglinger, C., Jansen, J., Lamers, J., and Stadler, G.A., 1989, Role of CCK in the regulation of gastric emptying and pancreatic secretion in man, Gastroenterology, 96: A159.Google Scholar
  16. Gamse, R., Petsche, U., Lembeck, F., and Jansco, G., 1982, Capsaicin applied to peripheral nerve inhibits axoplasmic transport of substance P and somatostatin, Brain Res., 239:447.PubMedCrossRefGoogle Scholar
  17. Green, T., and Dockray, G.J., 1988, Characterization of the peptidergic afferent innervation of the stomach in the rat, mouse and guinea pig, Neurosci., 25:181.CrossRefGoogle Scholar
  18. Green, T., Dimaline, R., and Dockray, G.J., 1989, Neuroendocrine control mechanisms of gastric emptying in the rat, in: “Nerves and the Gastrointestinal Tract,” M.V. Singer and H. Goebell, eds., Kluwar, Netherlands.Google Scholar
  19. Green, T., Dimaline, R., Peikin, S., and Dockray, G.J., 1988, The action of the cholecystokinin antagonist L364,718 on gastric emptying of liquid meals in the conscious rat, Am. J. Physiol., 255:G685.Google Scholar
  20. Grundy, D., and Scratcherd, T., 1989, Sensory afferents from the gastrointestinal tract, in: “Handbook of Physiology,” Volume 6, Chapter 10.Google Scholar
  21. Guth, P.H., and 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
  22. Guth, P.H., and Smith, E., 1977, Nervous regulation of the gastric microcirculation, in: “Nerves and the Gut,” F.P. Brooks and P.W. Ewers, eds., C.B. Stack, New York.Google Scholar
  23. Higashi, H., 1986, Pharmacological aspects of visceral sensory receptors, Progress in Brain Research, 67:149.PubMedCrossRefGoogle Scholar
  24. Holzer, P., 1988, Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides, Neurosci., 24:739.CrossRefGoogle Scholar
  25. Holzer, P., Taché, Y. and Guth, P.H., 1990, The vasodilator neuropeptides α-CGRP and VIP, but not substance P and neurokinin Ä, increase rat gastric mucosal blood flow, Gastroenterology, 98:A175.CrossRefGoogle Scholar
  26. Holzer, P., Peskar, B.M., Peskar, B.A., and Amman, R., 1990, Release of calcitonin gene-related peptide induced by capsaicin in the vascularly perfused rat stomach, Neurosci. Lett., 109:195.CrossRefGoogle Scholar
  27. Jansco, G., Kiraly, E., and Jansco-Gabor, A., 1980, Direct evidence for an axonal site of action of capsaicin, N.S. Arch. Pharmacol., 313:91.Google Scholar
  28. Jansco, G., and Such, G., 1983, Effects of capsaicin applied pe-rineurally to the vagus nerve on cardiovascular and respiratory functions in the cat, J. Physiol. Lond., 341:359.Google Scholar
  29. Ladenheim, E.E., Speth, R.C., and Ritter, R.C., 1988, Reduction of CCK-8 binding in the nucleus of the solitary tract in unilaterally nodosectomized rats, Brain Res., 474:125.PubMedCrossRefGoogle Scholar
  30. Leung, R.V., Guth, P.H., Scremin, O.U., Golanska, E.M., and Kauffman, G.L., Jr., 1984, Regional gastric mucosal blood flow measurements by hydrogen gas clearance in the anesthetized rat and rabbit, Gastroenterology, 87:28.PubMedGoogle Scholar
  31. Liddle, R.A., Green, G.M., Conrad, C.K., and Williams, J.A., 1986, Proteins but not amino acids, carbohydrates or fats stimulate cholecystokinin secretion in the rat, Am. J. Physiol., 251:G243.Google Scholar
  32. Liddle, R.A., Morita, E.T., Conrad, C.K., and Williams, J.A., 1986, Regulation of gastric emptying in humans by cholecystokinin, J. Clin. Invest., 77:992.PubMedCrossRefGoogle Scholar
  33. Lotti, V.J., Pendleton, R.G., Gould, R.J., Hanson, H.M., Chang, R.S., and Clineschmidt, B.V., 1987, In vivo pharmacology of L-364,718, a new potent nonpeptide cholecystokinin antagonist, J. Pharmacol. Exp. Ther., 241:103.PubMedGoogle Scholar
  34. Lundberg, J.M., and Saria, A., 1987, Polypeptide-containing neurons in airway smooth muscle, Ann. Rev. Physiol., 49:557.CrossRefGoogle Scholar
  35. Lynn, B., 1987, The immediate and long-term effects of applying capsaicin to cutaneous nerves, Acta Physiol. Hung., 69:287.PubMedGoogle Scholar
  36. Martinson, J., 1964, The effect of graded stimulating of efferent vagal nerve fibers on gastric motility, Acta Physiol. Scand., 62:256.PubMedCrossRefGoogle Scholar
  37. McCann, M.J., Hermann, G.E., and Rogers, R.C., 1989, Thyrotro-pin-releasing hormone: effects on identified neurons of the dorsal vagal complex, J. Auton. Nerv. System., 26:107.CrossRefGoogle Scholar
  38. Mei, N., 1985, Intestinal chemosensitivity, Physiol. Rev., 65:211.PubMedGoogle Scholar
  39. Moran, T.H., Smith, G.P., Hostetler, A.M., and McHugh, P.R., 1987, Transport of cholecystokinin (CCK) binding sites in subdiaphragmatic vagal branches, Brain Res., 415:149.PubMedCrossRefGoogle Scholar
  40. Morishito, T., and Guth, P.H., 1986, Vagal nerve stimulation causes noncholinergic dilatation of gastric arterioles, Am. J. Physiol., 250:G660.Google Scholar
  41. Murphy, R.B., Smith, G.P., and Gibbs, J., 1987, Pharmacological examination of cholecystokinin (CCK-8)-induced contractile activity in the rat isolated pylorus, Peptides, 8:127.PubMedCrossRefGoogle Scholar
  42. Okike, N., and Kelly, K.A., 1977, Vagotomy impairs pentagastrin-induced relaxation of canine gastric fundus, Am. J. Physiol., 232:E504.Google Scholar
  43. Pederson, R., O’Dorisio, T., Howe, T., Macintosh, B., Mueller, M., Brown, J., and Cataland, S., 1981, Vagal release of IR-VIP and IR-gastrin from the isolated perfused rat stomach, Mol. Cell. Endocrinol., 23:225.PubMedCrossRefGoogle Scholar
  44. Pendleton, R.G., Bendesky, R.J., Schaffer, L., Nolan, T.E., Gould, R.J., and Clineschmidt, B.V., 1987, Roles of endogenous cholecystokinin in biliary, pancreatic and gastric function: studies with L-364,718, a specific cholecystokinin receptor antagonist, J. Pharmacol. Exp. Ther., 241:110.PubMedGoogle Scholar
  45. Peter, E.T., Nicoloff, D.M., Leonard, A.S., Walder, A.L., and Wangensteen, O.H., 1963, Effect of vagal and sympathetic stimulation and ablation on gastric blood flow, JAMA, 183:1003.PubMedCrossRefGoogle Scholar
  46. Raybould, H.E. and Davison, J.S., 1989, Perivagal application of capsaicin abolishes the response of vagal gastric mechano-receptor to cholecystokinin, Soc. Neurosci., 15:973.Google Scholar
  47. Raybould, H.E., Holzer, P., Reddy, S.N., Yang, H. and Tache, Y., 1990, Capsaicin-sensitive vagal afferents contribute to gastric acid and vascular responses to intracisternal TRH analog, Peptides, in press.Google Scholar
  48. Raybould, H.E., Koelbel, C.B., Mayer, E.A. and Taché, Y., 1990, Inhibition of gastric motor function by circulating corti-cotropin-releasing factor in anaesthetized rats, J. Gastrointest. Motility, in press.Google Scholar
  49. 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
  50. Raybould, H.E., and Tache, Y., 1988, Cholecystokinin inhibits gastric motility and emptying via a capsaicin-sensitive vagal pathway in rats, Am. J. Physiol., 255:G242.Google Scholar
  51. Raybould, H.E., and Tache, Y., 1989, Gastric distension and histamine stimulate gastric acid secretion by capsaicin-sensitive vagal afferent pathway in the anesthetized rat, Eur. J. Pharmacol., 167:237.PubMedCrossRefGoogle Scholar
  52. Rogers, R.C, and McCann, M.J., 1989, Effects of TRH on the activity of gastric inflation-related neurons in the solitary nucleus in the rat, Neurosci. Lett., 104:71.PubMedCrossRefGoogle Scholar
  53. Rozsa, Z., Varro, A., and Jansco, G., 1985, Use of immunoblockade to study the involvement of peptidergic afferent nerves in the intestinal vasodilatory response to capsaicin in the dog, Europ. J. Pharmacol., 115:59.CrossRefGoogle Scholar
  54. Schiller, L.R., Walsh, J.H., and Feldman, M., 1980, Distension-induced gastrin release: effects of luminal acidification and intravenous atropine, Gastroenterology, 78:912.PubMedGoogle Scholar
  55. Smith, G.P., Falasco, J., Moran, T.H., Joyner, K.M.S., and Gibbs, J., 1988, CCK-8 decreases food intake and gastric emptying after pylorectomy or pyloroplasty, Am. J. Physiol., 255:R113.Google Scholar
  56. Sternini, C., Reeve, J.R., 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
  57. Swan, K.G., and Jacobson, E.D., 1967, Gastric mucosal blood flow and secretion in conscious dogs, Am. J. Physiol., 212:891.PubMedGoogle Scholar
  58. Tache, Y., Stephens, R.L., and Ishikawa, T., 1989, Central nervous system action of TRH to influence gastrointestinal function and ulceration, Ann. N.Y. Acad. Sci., 553:169.CrossRefGoogle Scholar
  59. Thiefin, G., Tache, Y., Leung, F.W., and Guth, P.H., 1989, CNS actions of thyrotropin-releasing hormone to increase gastric mucosal blood flow in the rat, Gastroenterology, 97:405.PubMedGoogle Scholar
  60. Thiefin, G., Raybould, H., Leung, F.W., Tache, Y., and Guth, P.H., 1990, Capsaicin-sensitive vagal afferent fibers contribute to gastric mucosal blood flow response to electrical stimulation, Am. J. Physiol., in press.Google Scholar
  61. Vagne, M., Konturek, S.J., and Chayvialle, J.A., 1982, Effect of vasoactive intestinal peptide on gastric secretion in the cat, Gastroenterology, 83:250.PubMedGoogle Scholar
  62. Wall, P.D., and Fitzgerald, M., 1981, Effects of capsaicin applied locally to adult peripheral nerve. I. Physiology of peripheral nerve and spinal cord, Pain, 11:363.PubMedCrossRefGoogle Scholar
  63. 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
  64. Yanigasawa, K., Yang, H., Walsh, J.H., and Tache, Y., 1990, Role of acetylcholine, histamine and gastrin in the acid response to intracisternal injection of TRH analog, RX77368, in the rat, Regul. Peptides, 27:161.CrossRefGoogle Scholar
  65. Yanigasawa, Y. and Tache, Y., 1990, Central vagal stimulation by intracisternal injection of TRH analog, RX77368 increases gastric histamine secretion in the rat, Gastroenterology, 98:A151.Google Scholar
  66. Yano, S.A., Fujiwara, A., Ozaki, Y., and Harada, M., 1983, Gastric blood flow responses to autonomic nerve stimulation and related pharmacological studies in rats, J. Pharm. Pharmacol., 35:641.PubMedCrossRefGoogle Scholar
  67. 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, 29:696.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Helen E. Raybould
    • 1
    • 2
  • Peter Holzer
    • 1
    • 2
  • Gerard Thiefin
    • 1
    • 2
  • Helge H. Holzer
    • 1
    • 2
  • Masashi Yoneda
    • 1
    • 2
  • Yvette F. Tache
    • 1
    • 2
  1. 1.Center for Ulcer Research and EducationVA West Los AngelesUSA
  2. 2.Department of Medicine and Brain Research InstituteUniversity of CaliforniaLos AngelesUSA

Personalised recommendations