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The Stomach pp 58-67 | Cite as

Trophic Effects of Gastrin: Therapeutic and Pathophysiological Implications

  • F. Halter
  • A. Schmassmann
Conference paper

Abstract

Gastrin is an important regulator of gastric acid secretion. In addition, it exerts well-defined trophic effects on the gastrointestinal tract which have long been linked to the pathogenesis of peptic ulcer disease [1, 2]. Moreover, hyper- gastrinaemia occurring during ulcer treatment with acid inhibitors is considered by many to be a risk factor fostering early ulcer relapse and development of malignant gastric tumours [for references see [3]]. Conversely, it has been postulated that as a growth factor gastrin could, in a manner analogous to epidermal growth factor, enhance re epithelialization of ulcers and possibly act as a mucosal protective factor [3].

Keywords

Acid Secretion Peptic Ulcer Disease Parietal Cell Trophic Effect Plasma Gastrin 
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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References

  1. 1.
    Johnson LR (1976) The trophic action of gastrointestinal hormone. Gastroenterology 70: 278–288PubMedGoogle Scholar
  2. 2.
    Walsh JH (1979) Pathogenic role for the gastrins. In: Rehfeld JF, Amdrup E (eds) Gastrins and the vagus. Academic, London, pp 181–198Google Scholar
  3. 3.
    Pounder R, Smith J (1990) Drug-induced changes of plasma gastrin concentration. In: Hunt RH (ed) Gastroenterology clinics of north america: peptic ulcer disease. Saunders, London, Vol 19, No. 1 pp 141–154Google Scholar
  4. 4.
    Wormsley KG, Grossman MI (1965) Maximal histology test in control subjects and patients with peptic ulcer. Gut 6:427–435PubMedCrossRefGoogle Scholar
  5. 5.
    Card WI, Marks IN (1960) The relationship between the acid output of the stomach following “maximal” histamine stimulation and parietal cell mass. Clin Sci 19: 147–163PubMedGoogle Scholar
  6. 6.
    Isenberg JI, Grossman MI, Maxwell V, Walsh JH (1975) Increased sensitivity to stimulation of acid secretion by pentagastrin in duodenal ulcer. J Clin Invest 55: 330–337PubMedCrossRefGoogle Scholar
  7. 7.
    Betrachini G (1988) Receptors involved in the regulation of gastric acid secretion. SAM J Suppl 74: 3–4Google Scholar
  8. 8.
    Smith JTL, Pounder RE, Nwokolo CU, Lanzon-Miller S, Evans DG, Graham DY, Evans DJ ( 1990 ] Inappropriate hypergastrinaemia in asymptomatic healthy subjects infected with Helicobacter pylori. Gut 311: 522–525CrossRefGoogle Scholar
  9. 9.
    Graham DY, Apekum A, Ginger PA-C, Lew PA, Doyle PA, Evans J et al (1990) Ablation of exaggerated meal-stimulated gastrin release in duodenal ulcer patients after clearance of Helicobacter ( Campylobacter) pylori infection. Am J Gastroent 85: 394–398PubMedGoogle Scholar
  10. 10.
    Levi S, Beardshall K, Swift I, Foulkes W, Playford R, Ghosh P, Calam J (1989) Antral Helicobacter pylori, hypergastrinaemia, and duodenal ulcers: effect of eradicating the organism. BMJ 29: 1504CrossRefGoogle Scholar
  11. 11.
    Chittajallu RS, Harwood J, Dorrian CA, McKoll KEL (1991) Is Helicobacter pylori related hypergastrinaemia due to the bacterium inhibiting parietal cell function? Gut 31: A1206Google Scholar
  12. 12.
    Willems G, Lehy T (1975) Radioautographic and quantitative studies on parietal and peptic cell kinetics in the mouse: a selective effect of gastrin on parietal cell proliferation. Gastroenterology 69: 416–425PubMedGoogle Scholar
  13. 13.
    Crean GP, Marshall MW, Rumsey RDE (1969) Parietal cell hyperplasia induced by the administration of pentagastrin (ICI 50, 123) to rats. Gastroenterology 57: 147–155PubMedGoogle Scholar
  14. 14.
    Lehy T, Bonnefond A, Dubrasquet M, Nasca S, Lewin M, Bonfils S (1973) Comparative effects of antrocolic transposition and antrectomy on fundic mucosa and acid secretion of the rat. Gastroenterology 64:421– 428PubMedGoogle Scholar
  15. 15.
    Witzel L, Halter F, Olah AJ, Häcki WH (1977) Effects of prolonged metiamide medication on the fundic mucosa. A secretory and histomorphometric study in the rat. Gastroenterology 73: 797–803PubMedGoogle Scholar
  16. 16.
    Alumets J, EL Munshid HA, Hakanson R, Liedberg G, Oscarson J, Rehfeld JF, Sundler F (1979) Effect of antrum exclusion on endocrine cells of rat stomach. J Physiol 286: 145–155PubMedGoogle Scholar
  17. 17.
    Hakanson R, Blom H, Carlsson E, Larsson H, Ryberg B, Sundler F (1986) Hypergastrinemia produces trophic effects in stomach but not in pancreas and intestines. Regulatory Peptides 13: 22. 5–233Google Scholar
  18. 18.
    Inauen W, Eigenmann F, Varga L, Koelz HR, Halter F (1990) Effects of gastric acid inhibition on plasma gastrin and oxyntic mucosal growth in the rat. Eur J Gastroenterol Hepatol 2: 297–303Google Scholar
  19. 19.
    Brenna E, Waldum HL, Sandwik AK, Schultze Sognen B, Kristensen (1992) Effects on the rat oxyntic mucosa of the histamine H2-antagonist loxtidine and the H+ K+ ATPase inhibitor omeprazole. Aliment Pharmacol Ther 6: 335–349PubMedCrossRefGoogle Scholar
  20. 20.
    Ekman L, Hansson E, Havu N, Lundberg C (1985) Toxicological studies on omeprazole. Scand J Gastroenterol 20 (suppl 108): 53–69CrossRefGoogle Scholar
  21. 21.
    Larsson H, Carlsson E, Mattsson H, Lundell L, Sundler F, Sundell G, Wallmark B, Watanabe T, Hankanson R (1986) Plasma gastrin and gastric enterochomaffinlike cell activation and proliferation. Studies with omeprazole and ranitidine in intact and antrectomized rats. Gastroenterology 90: 391–399PubMedGoogle Scholar
  22. 22.
    Chiverton SG, Hunt RH ( 1989 ] Initial therapy and relapse of duodenal ulcer: possible acid secretory mechanisms. Gastroenterology 96: 632–639PubMedGoogle Scholar
  23. 23.
    Fullarton GM, McLaughlan G, MacDonald A, Crean GP, McColl KEL (1989) Rebound nocturnal hypersecretion after four weeks treatment with an H2 antagonist. Gut 30:449– 454PubMedCrossRefGoogle Scholar
  24. 24.
    Marks IN, Johnston DA, Young GO (1991) Acid secretory changes and early relapse following duodenal ulcer healing with sucralfate, ranitidine, antacids or omeprazole. In: Halter F, Garner A, Tytgat CNJ (eds) Mechanisms of peptic ulcer healing. Kluwer, Dordrecht, pp 273–282Google Scholar
  25. 25.
    Yanaka A, Muto H (1988) Increased parietal cell responsiveness to tetragastrin in patients with recurrent duodenal ulcer. Dig Dis Sci 33: 1459–1465PubMedCrossRefGoogle Scholar
  26. 26.
    Marks IN (1991) Sucralfate: efficacy and basis for therapy. In: Swabb EA, Szabo S (eds), Ulcer disease-investigation and basis for therapy. Dekker, New York, pp 263–285Google Scholar
  27. 27.
    Bardhan K, Cole DS, Hawkins BW, Franks CR (1982) Does treatment with Cimetidine extended beyond initial healing of duodenal ulcer reduce the subsequent relapse rate? Br Med J 284:621– 623CrossRefGoogle Scholar
  28. 28.
    Prewett EJ, Hudson M, Nwokolo CU, Sawyer AFM, Pounder RE (1991) Nocturnal intragastric acidity during and after a period of dosing with either ranitidine or omeprazole. Gastroenterology 100: 873–877PubMedGoogle Scholar
  29. 29.
    Jones DB, Howden CW, Burget DW, Silletti C, Hunt RH (1988) Alteration of H2 receptor sensitivity in duodenal ulcer patients after maintenance treatment with an H2 receptor antagonist. Gut 29:890– 893PubMedCrossRefGoogle Scholar
  30. 30.
    Halter F (1990) H2-receptor antagonsits: intragastric acidity after repeated doses. Aliment Pharmacol Therap 4 (Suppl. 1): 1–6Google Scholar
  31. 31.
    Wilder-Smith CH, Halter F, Ernst T, Gennoni M, Zeyen B, Varga L, Roehmel J J, Merki HS (1990) Loss of acid suppression during dosing with H2 receptor antagonists. Aliment Pharmacol Therap 4 (Suppl 1): 15–27Google Scholar
  32. 32.
    Nwokolo CU, Smith JTL, Gavey C, Sawyerr A, Pounder RE (1990) Tolerance during 29 days of conventional dosing with cimetidine, nizatidine, famotidine or ranitidine. Aliment Pharmacol Therap 4 (Suppl 1):29– 45Google Scholar
  33. 33.
    Wilder-Smith CH, Ernst T, Gennoni M, Zeyen B, Halter F, Merki HS (1990) Tolerance to oral H2-receptor antagonists. Dig Dis Sci 35: 976–983PubMedCrossRefGoogle Scholar
  34. 34.
    Misiewicz JJ (1990) Clinical relevance to peptic ulcer healing and relapse. Aliment Pharmacol Therap 4 (Suppl 1): 85–96Google Scholar
  35. 35.
    Smith JTL, Gavey C, Nwokolo CU, Pounder RE (1990) Tolerance during 8 days of high dose H2 blockade: placebo-controlled studies of 24-hr acidity and gastrin. Aliment Pharmacol Therap 4 (Suppl 1):47– 63Google Scholar
  36. 36.
    Rogers MJ, Holmfield JHM, Primrose JN, Johnston D (1990) The effects of 15 days of dosing with placebo, sufotidine 600 mg nocte or 600 mg twice daily upon 24-hour intragastric acidity and 24-hour gastrin. Aliment Pharmacol Therap 4 (Suppl 1): 65–74Google Scholar
  37. 37.
    Hiirliman S. unpublished dataGoogle Scholar
  38. 38.
    Harvey RF, Bradshaw MJ, Davidson CM (1985) Multifocal gastric carcinoid tumours, achlorhydria, and hypergastrinaemia. Lancet i: 951–953Google Scholar
  39. 39.
    Borch K, Renvall H, Liedberg G (1985) Gastric endocrine cell hyperplasia and carcinoid tumours in pernicious anemia. Gastroenterology 88: 638–648PubMedGoogle Scholar
  40. 40.
    Bardram L, Thomsen P, Stadil F (1986) Gastric endocrine cells in omeprazole treated and untreated patients with the Zollinger-Ellison syndrome. Digestion 35 [Suppl 1): 116 –122PubMedCrossRefGoogle Scholar
  41. 41.
    Berlin RG [ 1991 ) Omeprazole. Gastrin and gastric endocrine cell data from clinical studies. Dig Dis Sci 36: 129–136PubMedCrossRefGoogle Scholar
  42. 42.
    Lanzon-Miller S, Pounder RE, Hamilton MR et al. (1987) Twenty-four hour intragastric acidity and plasma gastrin concentration in healthy subjects and patients with duodenal or gastric ulcer, or pernicious anaemia. Aliment Pharmacol Ther 1: 225–237PubMedCrossRefGoogle Scholar
  43. 43.
    Tarnawski, personal communicationGoogle Scholar
  44. 44.
    Okabe S, personal communicationGoogle Scholar
  45. 45.
    Takeuchi K, Johnson LR (1979) Pentagastrin protects against stress ulceration in rats. Gastroenterology 76: 327–334PubMedGoogle Scholar
  46. 46.
    Sakamoto T, Swierczek JS, Odgen D et al. (1985) Cytoprotective effect of pentagastrin and epidermal growth factor. Ann Surg 201: 290–295PubMedCrossRefGoogle Scholar
  47. 47.
    Takeuchi K, Johnson LR (1982) Effect of cell proliferation and loss in aspirin-induced gastric damage in the rat. Am J Physiol 243: G463–G468PubMedGoogle Scholar
  48. 48.
    Konturek SJ, Brzozowski T, Radecki I, et al. (1982) Cytoprotective effects of gastrointestinal hormones. In: Gut Peptides and Hormones. Biomedical Research Foundation, Tokyo, p 411Google Scholar
  49. 49.
    Horwell DC, Hughes J, Hunter JC, Pritchard MC, Richardson RS, Roberts E, Woodruff GN (1991) Rationally designed “dipeptoid” analogues of CCK. α-Methyl-tryptophan derivatives as highly selective and orally active gastrin and CCK-B antagonists with potent anxiolygic properties. J Med Chem 34: 404–414PubMedCrossRefGoogle Scholar
  50. 50.
    Lotti VJ, Chang RSL (1989) A new potent and selective non-peptide gastrin antagonist and brain cholecystokinin receptor (CCK–B) ligand: L-365,260. Eur J Pharmacol 162: 273–280PubMedCrossRefGoogle Scholar
  51. 51.
    Eissele R, Koop H, Patberg H, Rosskopf B, Frank M, Lorenz W, Arnold R (1991) The new gastric receptor antagonist Cam 1189 prevents ECL-cell hpyerplasia induced by the propton pump inhibitor BY 308 in the rat stomach. Europ J Gastroenterol Hepatol 3. Suppl, S34Google Scholar
  52. 52.
    Jacobson ED, Lindorf RH and Grossman MI (1966) Gastric secretion in relation to mucosal blood flow studied by a clearance technique. J Clin Invest 45: 1–13PubMedCrossRefGoogle Scholar
  53. 53.
    Ivarson IE, Darle N, Hulten L, Lindhagen J, Lundgren O (1982) Gastric blood flow and distribution: Effect of pentagastrin in anesthetized cat and man studied by an inert gas elimination technique. Scand J Gastroentol 17: 1037–1048Google Scholar
  54. 54.
    Schmassmann A, Varga L, Flogerzi B, Sanner M, Garner A, Halter F (1992) The gastrin receptor antagonist Cam-1189 is a partial secretory agonist in the stomach and pancreas of the rat. Gastroenterology 102 Suppl A160Google Scholar
  55. 55.
    Evangalista S, Maggi CA (1991) Protection induced by cholecystokin-8 (CCK-8) in ethanol-induced gastric lesions in mediated via vagal capsaicin-sensitive fibres and CCKA receptors. Br J Pharmacol 102: 119–122Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • F. Halter
  • A. Schmassmann

There are no affiliations available

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