Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells.
BACKGROUND
Different acid and peptic related gastroduodenal diseases are associated with both increased gastric secretion and Helicobacter pylori infection. Patients with H pylori associated gastritis or duodenal ulcer have increased serum pepsinogen levels which decrease after eradication. The mechanisms of H pylori induced gastric mucosal damage are not completely understood.


OBJECTIVE
To determine the effects of H pylori on pepsinogen secretion from isolated human peptic cells.


METHODS
Dispersed human peptic cells were prepared from endoscopically obtained biopsy specimens after collagenase digestion, mechanical disruption, and density gradient centrifugation. H pylori was obtained from gastric biopsies (antrum and body), and cultured in non-selective and selective media. Isolates of H pylori were used at different concentrations (1 - 20 x 10(6) colony forming units (cfu)).


RESULTS
H pylori (10(6) - 2 x 10(7) cfu) increased basal pepsinogen secretion in a concentration dependent manner. This stimulus was not observed with Escherichia coli. The increased secretion was in addition to that observed with 0.1 mM histamine and 0.1 mM dibutyryl-cyclic adenosine monophosphate. However, H pylori did not affect either carbamylcholine (0.1-10 microM) or cholecystokinin (1 microM) stimulated pepsinogen secretion. Addition of the nitric oxide synthase inhibitor N(w)-monomethyl-L-arginine (1 mM) inhibited H pylori induced cGMP generation and pepsinogen secretion, which were also reduced in the absence of extracellular calcium. H pylori induced pepsinogen secretion was not affected by the absence/presence of the cagA gene.


CONCLUSIONS
H pylori increases pepsinogen secretion from human peptic cells through a calcium and nitric oxide mediated intracellular pathway. This effect is independent of the H pylori virulent cagA gene, and may be a mechanism of H pylori induced gastric mucosal damage.
Lorente
S
S
Service of Gastroenterology, University Hospital, Zaragoza, Spain.
Doiz
O
O
Trinidad Serrano
M
M
Castillo
J
J
Lanas
A
A
D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D006152:Cyclic GMP / Q000378:metabolism; D004926:Escherichia coli / Q000502:physiology; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000378:metabolism*; D011863:Radioimmunoassay; D019323:omega-N-Methylarginine / Q000502:physiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D019323:omega-N-Methylarginine; D020116:Pepsinogen A; D006152:Cyclic GMP; D002118:Calcium