Stimulation of pepsinogen release from chief cells byHelicobacter pylori: evidence for a role of calcium and calmodulin

Abstract

To define the mechanisms by whichHelicobacter pyloristimulates pepsinogen secretion, thein vitrorelease of pepsinogen was studied using a preparation of pig chief cell monolayers.Helicobacter pyloriinduced a time- and concentration-dependent release of pepsinogen into the medium, with about a three-fold increase in pepsinogen secretion over controls found after 45 min of incubation. 3×107H. pylori produced 50% of the maximal response found at aH. pyloricount of 2×108. The action ofH. pyloridid not depend on the presence of the vacuolating toxin (vacA) and the cytotoxin-associated protein (cagA). Dibutyryl-cAMP and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate also markedly stimulated pepsinogen secretion and enhanced the stimulatory effect ofH. pylori. Helicobacter pylori-stimulated pepsinogen release was inhibited by lanthanum and the calmodulin antagonist W-7, but not by the L-type Ca2+channel blocker nifedipine, TMB-8, an agent that blocks the release of Ca2+from intracellular stores, the protein kinase C inhibitor staurosporine and the protein kinase A inhibitor H-8. It is suggested thatH. pyloridirectly stimulates pepsinogen release from gastric chief cells and that this effect is mediated via the calcium/calmodulin messenger branch.