Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+) ATPase

Nature volume 290, pages 159–161 (1981)Cite this article

Abstract

Studies both in vivo1,2 and in vitro1–5 have shown that substituted benzimidazoles inhibit the stimulation of acid secretion produced by dibutyryl cyclic AMP and histamine. Furthermore, the results differ from those produced by H2 antagonists and anticholinergic agents in that the inhibition is not competitive, and the site of action is intracellular and peripheral to that of dibutyryl cyclic AMP. To investigate the biochemical mechanism of action of substituted benzimidazoles, one such compound, H 149/94 (2-{ [2-(3-methyl)pyridyl-methyl]-sulphinyl]-5-methoxycarbonyl-6-methylbenzimidazol), has been tested either directly on an (H+ + K+) ATPase isolated from pig and human gastric mucosa or on the function of this enzyme in gastric glands isolated from rabbit and human gastric mucosa. (H+ + K+)ATPase6,7, which has only been found at the secretory surface of the parietal cell8, catalyses a one-to-one exchange of protons and potassium ions9–11. It is possibly the proton pump within the gastric mucosa, and may thus be the terminal or one of the terminal steps of the acid secretory process12,13. We show here that H 149/94 inhibits (H+ + K+)ATPase, which may explain its inhibitory action on acid secretion in vitro and in vivo. Because of the unique distribution and properties of the (H+ + K+) ATPase, the inhibitory action of H 149/94 on this enzyme may be a highly selective clinical means of suppressing the acid secretory process.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Fellenius, E. et al. in Hydrogen Ion Transport in Epithelia (eds Schulz, I., Sachs, G., Forte J & Ullrich, K. J.) 193–202 (Elsevier, Amsterdam, 1980).

    Google Scholar 

  2. Olbe, L., Sjöstrand, S.-E. & Fellenius, E. in Gastrins and the Vagus (eds Rehfeld, J. F. & Amdrup, E.) 245–250 (Academic, New York, 1979).

    Google Scholar 

  3. Sjöstrand, S.-E., Ryberg, B. & Olbe, L. Acta physiol. scand. spec. Suppl., 181–185 (1978).

  4. Olbe, L. et al. Scand. J. Gastroenterol. Suppl. 55, 131–133 (1979).

    CAS  Google Scholar 

  5. Fellenius, E. et al. in Hormone Receptors in Digestion and Nutrition (eds Rosselin, G., Fromageot, P . & Bonfils, S.) 355–360 (Elsevier, Amsterdam, 1979).

    Google Scholar 

  6. Lee, J., Simpson, G. & Scholes, P. Biochem. biophys. Res. Commun. 60, 825–832 (1974).

    Article  CAS  Google Scholar 

  7. Ray, T. K. & Forte, J. G. Biochim. biophys. Acta 443, 451–467 (1976).

    Article  CAS  Google Scholar 

  8. Saccomani, G. et al. J. Cell Biol 83, 271–283 (1979).

    Article  CAS  Google Scholar 

  9. Shackman, R., Schwartz, A., Saccomani, G. & Sachs, G. J. Membrane Biol. 32, 361–381 (1977).

    Article  Google Scholar 

  10. Sachs, G., Chang, H. M., Rabon, E., Schackman, R. & Saccomani, G. J. biol. Chem. 251, 7690–7698 (1976).

    CAS  PubMed  Google Scholar 

  11. Chang, H., Saccomani, G., Rabon, E., Shackman, R. & Sachs, G. Biochim. biophys. Acta 464, 313–327 (1977).

    Article  CAS  Google Scholar 

  12. Sachs, G. et al. Gastroenterology 71, 931–931 (1977).

    Google Scholar 

  13. Forte, J. G. & Lee, H. C. Gastroenterology 73, 921–927 (1977).

    CAS  PubMed  Google Scholar 

  14. Berglindh, T. & Öbrink, K.-J. Acta physiol. scand. 96, 150–159 (1976).

    Article  CAS  Google Scholar 

  15. Berglindh, T. Biochim. biophys. Acta 464, 217–233 (1977).

    Article  CAS  Google Scholar 

  16. Chew, C. S., Hersey, S. J., Sachs, G. & Berglindh, T. Am. J. Physiol. 238, 312–320 (1980).

    Google Scholar 

  17. Berglindh, T., Helander, H. F. & Sachs, G. Scand. J. Gastroenterol. Suppl. 55, 7–15 (1979).

    CAS  Google Scholar 

  18. Berglindh, T., Dibona, D. R., Ito, S. & Sachs, G. Am. J. Physiol. 238, G 165–G 176 (1980).

    CAS  Google Scholar 

  19. Soll, A., Am. J. Physiol. 238, G 366–G 375 (1980).

    CAS  Google Scholar 

  20. Saccomani, G., Stewart, H. B., Shaw, D., Lewin, M. & Sachs, G. Biochim. biophys. Acta 465, 311–330 (1977).

    Article  CAS  Google Scholar 

  21. Rabon, E., Chang, H. & Sachs, G. Biochemistry 17, 3345–3353 (1978).

    Article  CAS  Google Scholar 

  22. Fiske, C. H. & Subbarow, Y. J. Biol. Chem. 66, 375–100 (1925).

    CAS  Google Scholar 

  23. Mårdh, S. Biochim. biophys. Acta 391, 448–463 (1975).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Laboratories, AB Hässle, S-43183, Mölndal, Sweden

    Erik Fellenius, Berit Elander, Sven-Erik Sjöstrand & Björn Wallmark

  2. Department of Physiology and Medical Biophysics, Biomedical Centre, Uppsala University, S-75105, Uppsala, Sweden

    Thomas Berglindh

  3. Laboratory of Membrane Biology, University of Alabama in Birmingham, Birmingham, Albama, 35294, USA

    George Sachs

  4. Sahlgrenska Hospital, Surgical Clinic II, S-41345, Gothenburg, Sweden

    Lars Olbe

Authors
  1. Erik Fellenius
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Berglindh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George Sachs
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lars Olbe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Berit Elander
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sven-Erik Sjöstrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Björn Wallmark
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fellenius, E., Berglindh, T., Sachs, G. et al. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+) ATPase. Nature 290, 159–161 (1981). https://doi.org/10.1038/290159a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/290159a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing