Molecular and Cellular Regulation of the Gastric Proton Pump

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  • Asano Shinji
    Life Scientific Research Center, Toyama Medical and Pharmaceutical University
  • Morii Magotoshi
    Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University
  • Takeguchi Noriaki
    Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University

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Abstract

The gastric H+,K+-ATPase is a proton pump that is responsible for gastric acid secretion and that actively transports protons and K+ ions in opposite directions to generate in excess of a million-fold proton gradient across the membrane under physiological conditions. This pump is also a target molecule of proton pump inhibitors which are used for the clinical treatment of hyperacidity. In this review, we wish to summarize the molecular regulation of this pump based on mutational studies, particularly those used for the identification of binding sites for cations and specific inhibitors. Recent reports by Toyoshima et al. (2000, 2002) presented precise three-dimensional (3-D) structures of the sarcoplasmic reticulum (SR) Ca2+-ATPase, which belongs to the same family as the gastric H+,K+-ATPase. We have studied the structure–function relationships for the gastric H+,K+-ATPase using 3-D structures constructed by homology modeling of the related SR Ca2+-ATPase, which was used as a template molecule. We also discuss in this review, the regulation of cell surface expression and synthesis control of the gastric proton pump.

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