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


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.

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  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 

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Fellenius, E., Berglindh, T., Sachs, G. et al. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+) ATPase. Nature 290, 159–161 (1981).

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