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Ammonia and gastric acid secretion: a key to understanding activity and regulation of the H+,K+-ATPase

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Abstract

Ammonia is a cytotoxic substance liberated during Helicobacter pylori infection that may be responsible, in part, for the significant reduction in gastric acid secretion in human patients. However, it is not clear how ammonia blocks acid secretion. Here, we investigate several potential pathways for ammonia blockade in gastric oxyntic cells.___TAGSTART___BR___TAGEND___ Methods: Stomachs from the bullfrog, Rana catesbeiana, were stripped and mounted in Ussing chambers. Four possible pathways of blockade were investigated: (1) blockade of basolateral K+-channel activity, (2) blockade of ion transport activity, (3) neutralization of secreted H+ or (4) ATP depletion.___TAGSTART___BR___TAGEND___ Results: Addition of nutrient 10 mM NH4Cl at pH 7.4, yielding 92.5 μM NH3 and 9.91 mM NH4 +, abolished acid secretion within 30 min. Inhibition of acid secretion did not occur by blockade of basolateral K+-channel activity or ion transport activity, nor did NH4 + enter cells by substituting for Na+ or K+ on individual ion transporters. Furthermore, neutralization of the luminal solution by NH3 and/or ATP depletion cannot account for the total reduction in acid secretion. We demonstrate that NH4Cl acts specifically on stimulated tissues.___TAGSTART___BR___TAGEND___ Conclusions: We show that small concentrations of ammonia completely block gastric acid secretion. We propose that inhibition of acid secretion occurs by blockade of an apical K+-channel, specifically inwardly rectifying K+-channels. Our data suggest that apical K+-channel activity may be essential for the regulation of acid secretion and could be a new therapeutic target for acid inhibitory drugs.

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  1. Susan J. Hagen
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Hagen, S.J. Ammonia and gastric acid secretion: a key to understanding activity and regulation of the H+,K+-ATPase. Inflammopharmacology 10, 471–481 (2002). https://doi.org/10.1163/156856002321544936

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