doi:10.1136/gut.50.1.13engLorente, S.Doiz, O.Serrano, M.T.Castillo, J.Lanas, A.Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells.ART-2002-51932Background: 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. Aim: 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 (1–20×106 colony forming units (cfu)). Results: H pylori (106–2×107 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 μM) or cholecystokinin (1 μM) stimulated pepsinogen secretion. Addition of the nitric oxide synthase inhibitor Nw-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.2002http://zaguan.unizar.es/record/13027510.1136/gut.50.1.13http://zaguan.unizar.es/record/130275oai:zaguan.unizar.es:130275GUT 50, 1 (2002), 13-8All rights reservedhttp://www.europeana.eu/rights/rr-f/info:eu-repo/semantics/closedAccess