title: Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells.
abstract: 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.
authors.affiliation: Service of Gastroenterology, University Hospital, Zaragoza, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Lorente
authors.forename: O
authors.initials: O
authors.lastname: Doiz
authors.forename: M
authors.initials: M
authors.lastname: Trinidad Serrano
authors.forename: J
authors.initials: J
authors.lastname: Castillo
authors.forename: A
authors.initials: A
authors.lastname: Lanas
mesh_terms: 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
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C080866:cagA protein, Helicobacter pylori; D019323:omega-N-Methylarginine; D020116:Pepsinogen A; D006152:Cyclic GMP; D002118:Calcium