Stimulation of pepsinogen release from chief cells by Helicobacter pylori: evidence for a role of calcium and calmodulin.
To define the mechanisms by which Helicobacter pylori stimulates pepsinogen secretion, the in vitro release of pepsinogen was studied using a preparation of pig chief cell monolayers. Helicobacter pylori induced 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. 3x10(7) H. pylori produced 50% of the maximal response found at a H. pylori count of 2x10(8). The action of H. pylori did 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 of H. 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 that H. pylori directly stimulates pepsinogen release from gastric chief cells and that this effect is mediated via the calcium/calmodulin messenger branch.
Beil
W
W
Department of General Pharmacology, Medizinische Hochschule Hannover, Hannover, Germany.
Wagner
S
S
Piller
M
M
Heim
H K
HK
Sewing
K F
KF
D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D019872:Chief Cells, Gastric / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016480:Helicobacter pylori / Q000254:growth & development / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007811:Lanthanum; D009543:Nifedipine / Q000494:pharmacology; D020116:Pepsinogen A / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013552:Swine; D013997:Time Factors
D002147:Calmodulin; D007546:Isoquinolines; D013449:Sulfonamides; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C017967:W 7; D007811:Lanthanum; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D020116:Pepsinogen A; D019311:Staurosporine; D009543:Nifedipine; D002118:Calcium