Histamine and Helicobacter pylori: are we closer to the answer?

  • J. Calam
  • P. Bliss
  • S. Murray
  • G. Taylor


The discovery of Helicobacter pylori initially diminished interest in gastric acid, but this proved temporary. It is now generally believed that the effect of the infection on acid secretion determines the disease outcome. Patients who respond to the infection with acid hypersecretion are likely to develop duodenal ulcer1, while those who develop hyposecretion are at risk of gastric cancer2. These changes in acid secretion are reversed by eradicating the infection. The effect of H. pylori on acid secretion is also relevant to therapy. Proton-pump inhibitors inhibit acid secretion to a greater extent in those who are infected3, while increasing gastritis in the corpus of the stomach4. Therefore it remains important to understand the factors which control acid secretion. The role of gastric mucosal histamine in the regulation of acid secretion was debated extensively until selective histamine H2-receptor antagonists revealed its crucial role. However, the matter has now become less clear once again. Firstly, in addition to H1 and H2 receptors it is now appreciated that various cells in the gastric mucosa carry histamine H3 receptors whose location and effects are still being defined5. Secondly, it is now appreciated that agonists of histamine receptors are produced not only by the enterochromaffin-like (ECL) cells present in gastric corpus mucosa, but also by mast cells which are more abundant in H. pylori infection6, and by H. pylori bacteria themselves in the form of Nα-methylhistamine7


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  1. 1.
    El-Omar EM, Penman ID, Ardill JES, Chittajallu RS, Howie C, McColl KEL. Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease. Gastroenterology. 1995;109:681–91.PubMedCrossRefGoogle Scholar
  2. 2.
    El-Omar E, Oien K, El-Nujumi A et al. H. pylori-induced hypochlorhydria is associated with increased risk of gastric cancer. Gastroenterology. 1997;112:A558.Google Scholar
  3. 3.
    Verdu EF, Armstrong D, Idstrom JP et al. Effect of curing Helicobacter pylori infection on intragastric pH during treatment with omeprazole. Gut. 1995;37:743–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Logan RPH, Walker MM, Misiewicz JJ, Gummett PA, Karim QN, Baron JH. Changes in the intragastric distribution of Helicobacter pylori during treatment with omeprazole. Gut. 1995;36:12–16.PubMedCrossRefGoogle Scholar
  5. 5.
    Prinz C, Kajimura M, Scott DR, Mercier F, Helander HF, Sachs G. Histamine secretion from rat enterochromaffin-like cells. Gastroenterology. 1993;105:449–61.PubMedGoogle Scholar
  6. 6.
    Nakajima S, Krishnan B, Ota H et al. Mast cell involvement in gastritis with or without Helicobacter pylori infection. Gastroenterology. 1997;113:746–54.PubMedCrossRefGoogle Scholar
  7. 7.
    Courillon Mallet A, Launay JM, Roucayrol AM et al. Helicobacter pylori infection: physiopathologic implication of N alpha-methyl histamine. Gastroenterology. 1995;108:959–66.PubMedCrossRefGoogle Scholar
  8. 8.
    Lonroth H, Hakanson R, Lundell L, Sundler F Histamine containing endocrine cells in the human stomach. Gut. 1990;31:383–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Sachs G, Zeng N, Prinz C. Physiology of isolated gastric endocrine cells. Annu Rev Physiol. 1997;59:243–56.PubMedCrossRefGoogle Scholar
  10. 10.
    Saperas E. The role of mast cells in gastrointestinal inflammation. Gastroenterology. 1996;110:1656–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Man WK, Saunders JH, Ingoldby C, Spencer J. Effect of cimetidine on the amounts of histamine in the gastric mucosa of patients with gastric or duodenal ulcers. Gut. 1981;22:923–6.PubMedCrossRefGoogle Scholar
  12. 12.
    Peden NR, Callachan H, Shepherd DM, Wormsley KG. Gastric mucosal histamine and histamine methyltransferase in patients with duodenal ulcer. Gut. 1982;23:58–62.PubMedCrossRefGoogle Scholar
  13. 13.
    Thon KP, Lorenz W, Obmann C, Weber D, Rohde H, Roher HD. Sample taking problems in measuring actual histamine levels of human gastroduodenal mucosa: specific and general relevance in clinical trials on peptic ulcer pathogenesis and selective proximal vagotomy. Gut. 1985;26:1165–78.PubMedCrossRefGoogle Scholar
  14. 14.
    Man WK, Thompson JN, Baron JH, Spencer J. Histamine and duodenal ulcer: effect of omeprazole on gastric histamine in patients with duodenal ulcer. Gut. 1986;27:418–22.PubMedCrossRefGoogle Scholar
  15. 15.
    Lonroth H, Rosengren E, Olbe L, Lundell L. Histamine metabolism in human gastric mucosa. Effect of pentagastrin stimulation. Gastroenterology. 1990;98:921–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Lonroth H, Rosengren E, Lundell L. The role of the antrum and the vagus nerve in the metabolism of histamine in the human gastric mucosa. Scand J Gastroenterol. 1991;26:827–38.PubMedCrossRefGoogle Scholar
  17. 17.
    Brzezinska Blaszczyk E, Romanski B, Bartuzi Z, Zbikowska Gotz M, Pietrzak A, Staszynska M. Anaphylactic histamine release from human gastric and duodenal mast cells. J Invest Allergol Clin Immunol. 1994;4:242–5.Google Scholar
  18. 18.
    Baenkler HW, Mitznegg P, Domschke S et al. Secretin-induced histamine release in duodenal-ulcer patients. Lancet. 1977;1:928–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Queiroz DM, Mendes EN, Rocha GA et al. Helicobacter pylori and gastric histamine concentrations. J Clin Pathol. 1991;44:612–13.PubMedCrossRefGoogle Scholar
  20. 20.
    Queiroz DM, Mendes EN, Rocha GA et al. Histamine content of the oxyntic mucosa from duodenal ulcer patients: effect of Helicobacter pylori eradication. Am J Gastroenterol. 1993;88:1228–32.PubMedGoogle Scholar
  21. 21.
    Queiroz DM, Mendes EN, Rocha GA, Barbosa AJ, Carvalho AS, Cunha Melo JR. Histamine concentration of gastric mucosa in Helicobacter pylori positive and negative children. Gut. 1991;32:464–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Bechi P, Romagnoli P, Bacci S et al. Helicobacter pylori and duodenal ulcer: evidence for a histamine pathways-involving link. Am J Gastroenterol. 1996;91:2338–43.PubMedGoogle Scholar
  23. 23.
    Kidd M, Miu K, Tang LH et al. Helicobacter pylori lipopolysaccharide stimulates histamine release from rat enterochromaffin like cells. Gastroenterology. 1997;113:1110–17.PubMedCrossRefGoogle Scholar
  24. 24.
    Prinz C, Neumayer N, Mahr S, Classen M, Schepp W Functional impairment of rat enterochromaffin-like cells by interleukin 1 beta. Gastroenterology. 1997;112:364–75.PubMedCrossRefGoogle Scholar
  25. 25.
    Lutton DA, Bamford KB, O’Loughlin B, Ennis M Modulatory action of Helicobacter pylori on histamine release from mast cells and basophils in vitro. J Med Microbiol. 1995;42:386–93.PubMedCrossRefGoogle Scholar
  26. 26.
    Bechi P, Dei R, Di Bello MG, Masini E. Helicobacter pylori potentiates histamine release from serosal rat mast cells in vitro. Dig Dis Sci. 1993;38:944–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Aceti A, Celestino D, Caferro M et al. Basophil-bound and serum immunoglobulin E directed against Helicobacter pylori in patients with chronic gastritis. Gastroenterology. 1991;101:131–7.PubMedGoogle Scholar
  28. 28.
    Velasquez RD, Brunner G, Varrentrapp M, Tsikas D, Frolich JC. Helicobacter pylori produces histamine and spermidine. Z Gastroenterol. 1996;34:116–22.PubMedGoogle Scholar
  29. 29.
    Vuyyuru L, Schubert ML, Harrington L, Arimura A, Makhlouf GM. Dual inhibitory pathways link antral somatostatin and histamine secretion in human, dog, and rat stomach. Gastroenterology. 1995;109:1566–74.PubMedCrossRefGoogle Scholar
  30. 30.
    Beales IL, Calam J. Effect of N alpha-methyl-histamine on acid secretion in isolated cultured rabbit parietal cells: implications for Helicobacter pylori-associated gastritis and gastric physiology. Gut. 1997;40:14–19.PubMedGoogle Scholar
  31. 31.
    Bliss PW, Calam J. The effects of Nalpha-methylhistamine on gastric acid secretion in human volunteers. Gut. 1997;40(Suppl. 1):Al.Google Scholar
  32. 32.
    Bliss PW, Healey ZV, Jordinson M, Arebi N, Hussain Z, Calam J. Nalpha methylhistamine releases gastrin from isolated rabbit G cells via an H2 receptor dependent mechanism. Regul Peptides. 1997;71:49.Google Scholar
  33. 33.
    Gillen D, El-Omar E, McColl KEL. Parietal cell sensitivity to gastrin distinguishes H. pylori-infected DU patients from infected healthy volunteers. Gastroenterology. 1998(In press)(abstract).Google Scholar
  34. 34.
    Kuipers EJ, Pena AS, Van Kamp G et al. Seroconversion for Helicobacter pylori. Lancet. 1993;342:328–31.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1998

Authors and Affiliations

  • J. Calam
  • P. Bliss
  • S. Murray
  • G. Taylor

There are no affiliations available

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