Direct effects of proton pump inhibitors on histamine release from rat enterochromaffin-like cells

Abstract

Enterochromaffin-like (ECL) cells play a central role in the regulation of gastric acid secretion. Previous studies have shown that proton pump inhibitors accelerate histamine release from ECL cells through the effects of gastrin. However, direct effects of proton pump inhibitors on ECL cells have not been demonstrated to date because the indirect effects of gastrin are difficult to suppress. We investigated the direct effects of proton pump inhibitors medication on ECL cells using an elutriation system. ECL cells were stimulated with gastrin or rabeprazole, and histamine release from ECL cells was measured. Rabeprazole increased histamine release through a pathway that differed from that of gastrin. The histamine increase was likely due to an acceleration of vesicular monoamine transporter 2 (VMAT2). Rabeprazole increased histamine release from ECL cells directly via VMAT2, but did not affect the total amount of histamine in the cells. The results suggest that patients receiving proton pump inhibitors for extended periods must be monitored extensively because gastric tumor proliferation may be promoted by increased histamine release from ECL cells.