Skip to main content
Log in

Profound increase ofHelicobacter pylori urease activity in gastric antral mucosa at low pH

  • Esophageal, Gastric, And Duodenal Disorders
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The effect of pH onH. pylori urease activity in its ecological niche was studied in gastric antral biopsy specimens. Specimens were incubated in 10 mmol/liter urea solutions at pH range 3.3–8.2. Activity of urease was studied by measuring production of ammonia and change in pH of the solutions. Urease activity was reduced at pH 8.2 (1424 ± 218 µmol/liter) but decreasing initial pH to neutral and acidic values resulted in significant maximal 6.5-fold increase in ammonia production (9491 ± 1073 µmol/liter,P<0.0005), which considerably raised the pH of the test solutions. Peak urease activity was between pH 5.0 and 7.0. In contrast to specimens incubated initially at pH 8.0, reincubation of washed specimens from solutions with initial pH 7.0 showed eightfold decreased urease activity. It is concluded that urease activity is markedly pH dependent with pH optima below the physiological mucosal surface pH. Furthermore, availability of urease is limited. Thus, an impaired gastric mucosal integrity allowing back diffusion of hydrogen ions may release urease activity, which might further weaken the mucus barrier and damage the gastric epithelium.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Goodwin CS, Armstrong JA, Marshall BJ:Campylobacter pyloridis, gastritis, and peptic ulceration. J Clin Pathol 39:353–365, 1986

    Google Scholar 

  2. Rauws EAJ, Langenberg W, Houthoff HJ, Zanen HC, Tytgat GNJ:Campylobacter pyloridis-associated chronic active antral gastritis. Gastroenterology 94:33–40, 1988

    Google Scholar 

  3. Megraud F: Epidemiology ofHelicobacter pylori infection. Gastroenterol Clin North Am 22:(1)73–88, 1993

    Google Scholar 

  4. Hessey SJ, Spencer J, Wyatt JI, Sobala G, Rathbone BJ, Axon AT, Dixon MF: Bacterial adhesion and disease activity inHelicobacter-associated chronic gastritis. Gut 31:134–138, 1990

    Google Scholar 

  5. Allen A, Flemström G, Garner A, Kivilaakso E: Gastroduodenal mucosal protection. Physiol Rev 73:(4)823–857, 1993

    Google Scholar 

  6. Dunn BE, Roop II RM, Sung CC, Sharma SA, Perez-Perez GI, Blaser MJ: Identification and purification of a cpn60 heat shock protein homolog fromHelicobacter pylori. Infect Immun 60:1946–1951, 1992

    Google Scholar 

  7. Eaton KA, Morgan DR, Krakowka S: Motility as a factor in the colonization of gnotobiotic piglets byHelicobacter pylori. J Med Microbiol 37:123–127, 1992

    Google Scholar 

  8. Fauchere JL, Blaser MJ: Adherence ofHelicobacter pylori cells and its surface components to HeLa cell membranes. Microb Pathogen 9:1–13, 1990

    Google Scholar 

  9. Ferrero RL, Lee A: The importance of urease in acid protection for the gastric-colonizing bacteriaHelicobacter pylori andH. felis sp. nov. Microb Ecol Health Dis 4:121–134, 1991

    Google Scholar 

  10. Leunk RD: Production of a cytotoxin byHelicobacter pylori. Rev Infect Dis 13(suppl 8):686–689, 1991

    Google Scholar 

  11. Marshall BJ, Barrett LJ, Prakash C, McCallum RW, Guerrant RL: Urea protectsHelicobacter (Campylobacter) pylori from the bactericidal effect of acid. Gastroenterology 99:697–702, 1990

    Google Scholar 

  12. Sidebotham RL, Batten JJ, Karim QN, Spencer J, Baron JH: Breakdown of gastric mucus in presence ofHelicobacter pylori. J Clin Pathol 44:52–57, 1991

    Google Scholar 

  13. Hu LT, Mobley HLT: Purification andN-terminal analysis of urease fromHelicobacter pylori. Infect Immun 58:992–998, 1990

    Google Scholar 

  14. Perez-Perez GI, Olivares AZ, Cover TL, Blaser MJ: Characteristics ofHelicobacter pylori variants selected for urease deficiency. Infect Immun 60:3658–3663, 1992

    Google Scholar 

  15. Eaton KA, Brooks CL, Morgan DR, Krakowka S: Essential role of urease in pathogenesis of gastritis induced byHelicobacter pylori in gnotobiotic piglets. Infect Immun 59:2470–2475, 1991

    Google Scholar 

  16. McColm AA, Bagshaw J, O'Malley C, McClaren A: Is urease a lethal target for therapy ofHelicobacter pylori? Microb Ecol Health Dis 4(S):S145, 1991

    Google Scholar 

  17. Smoot DT, Mobley HLT, Chippendale JF, Lewison JF, Resau JH:Helicobacter pylori urease is toxic to human gatstric epithelial cells. Infect Immun 58:1992–1994, 1990

    Google Scholar 

  18. Hazell SL, Opekun AR, Graham DY: Survival ofCampylobacter pylori in acidic environments is independent of urease activity. Gastroenterology 96:A201, 1989

    Google Scholar 

  19. Goldie J, Jalali S, Hunt RH, Richardson-McMaster MR: Study of media and pH requirements for the growth ofCampylobacter pylori. Gastroenterology 94:(5)A150, 1988

  20. Rathbone BJ, West AP, Wyatt JI, Johnson AW, Tompkins DS, Heatley RV:Campylobacter pyloridis, urease, and gastric ulcers. Lancet 12:400–401, 1986

    Google Scholar 

  21. DaFonseca-Wollheim F: Die direkte Plasmaammoniak-Bestimmung ohne Enteiweissung. Klin Chem Klin Biochem 11:426, 1973

    Google Scholar 

  22. Loffeld RL, Stobberingh E, Arends JW: A review of diagnostic techniques forHelicobacter pylori infection. Dig Dis Sci 11:173–180, 1993

    Google Scholar 

  23. Kawano S, Tsuji M, Sato N, Kamada T: A role of ammonia inCampylobacter pylori induced gastric mucosal damage. Gastroenterology 96:A252, 1988 (abstract)

    Google Scholar 

  24. Armstrong WM: Cellular mechanisms of ion transport in the small intestine.In Physiology of the Gastrointestinal Tract. LR Johnson (ed). New York, Raven Press, 1987, pp 1251–1270

    Google Scholar 

  25. Takeuchi K, Ohuchi T, Harada H, Okabe S: Irritant and protective action of urea-urease ammonia in rat gastric mucosa. Different effects of ammonia and ammonium ion. Dig Dis Sci 40:(2)274–281, 1995

    Google Scholar 

  26. Murakami M, Saita H, Teramura S, Dekigai H, Asagoe K, Kusaka S, Kita T: Gastric ammonia has a potent ulcerogenic action on the rat stomach. Gastroenterology 105:1710–1715, 1993

    Google Scholar 

  27. Riddell RH:Helicobacter pylori—some what, why, and how morphologic issues. Scand J Gastroenterol 26(suppl 187):87–84, 1991

    Google Scholar 

  28. Turnberg LA: Gastric mucus, bicarbonate and pH gradients in mucosal protection. Clin Invest Med 10:178–180, 1987

    Google Scholar 

  29. Wallace JL, Bell CJ: Gastroduodenal mucosal defense. Curr Opin Gastroenterol 9:902–908, 1993

    Google Scholar 

  30. Rapier RC, Dreilinger AD, Nyberg LM, Koss MA, Hogan DL, Isenberg JI:Helicobacter pylori diminishes proximal duodenal mucosal bicarbonate secretion in patients with duodenal ulcer disease. Gastroenterology 106:(4)A164, 1994 (abstract)

  31. Cussac V, Ferrero RL, Labigne A: Expression ofHelicobacter pylori urease genes inEscherichia coli grown under nitrogen-limiting conditions. J Bacteriol 174:2466, 1992

    Google Scholar 

  32. Evans DJ, Evans DG, Kirkpatrick SS, Graham DY: Characterization of theHelicobacter pylori urease and purification of its subunits. Microb Pathogen 10:15–26, 1991

    Google Scholar 

  33. Ormand JE, Talley NJ:Campylobacter pylori, mucus, and peptic ulceration. A dynamic interaction. J Clin Gastroenterol 5:492–495, 1989

    Google Scholar 

  34. Bauerfeind P, Foxall P, McDuff R, Mobley HLT: Expression and release ofHelicobacter pylori urease at various pH levels. Am J Gastroenterol 89:(8)1285, 1994 (abstract)

    Google Scholar 

  35. Talley NJ, Ormand JE, Frie CA, Zinsmeister AR: Stability of pH gradientsin vivo across the stomach inHelicobacter pylori gastritis, dyspepsia, and health. Am J Gastroenterol 87:(5)590–594, 1992

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This study was supported by the Deutsche Forschungsgemeinschaft (Mi 190/3).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Miederer, S.E., Grübel, P. Profound increase ofHelicobacter pylori urease activity in gastric antral mucosa at low pH. Digest Dis Sci 41, 944–949 (1996). https://doi.org/10.1007/BF02091535

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02091535

Key words

Navigation