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

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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.

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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

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  1. Erik Fellenius
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  2. Thomas Berglindh
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  3. George Sachs
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  4. Lars Olbe
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  5. Berit Elander
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  6. Sven-Erik Sjöstrand
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  7. Björn Wallmark
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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). https://doi.org/10.1038/290159a0

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