title: Helicobacter pylori vacuolating cytotoxin inhibits duodenal bicarbonate secretion by a histamine-dependent mechanism in mice.
abstract: BACKGROUND
  The pathogenic mechanisms involved in Helicobacter pylori-induced duodenal mucosal injury are incompletely understood. In the present study, we sought to investigate the effect of H. pylori vacuolating cytotoxin (VacA) on duodenal mucosal bicarbonate (HCO3-) secretion.
  
  
  METHODS
  Concentrated bacterial culture supernatants from an H. pylori wild-type strain producing VacA with s1/m1 genotypes (P12) and from an isogenic mutant lacking VacA (P12DeltavacA) were used. HCO3- secretion by murine duodenal mucosa was examined in vitro in Ussing chambers. Duodenal mucosal histamine release was measured using enzyme-linked immunosorbent assay. The expression of histamine H2 receptor was examined by immunohistochemical analysis.
  
  
  RESULTS
  In a dose-dependent manner, the VacA-positive supernatant P12 reduced prostaglandin E2 (PGE2)-stimulated duodenal mucosal HCO3- secretion to a maximum of 49% (P<.0001), whereas P12DeltavacA did not result in significant inhibition (P>.05). Purified VacA had a similar effect. Histamine H2 receptor antagonists attenuated the effect of P12 on PGE2-induced HCO3- secretion. P12 stimulated duodenal histamine release in a dose-dependent manner, and exogenous histamine inhibited PGE2-stimulated duodenal HCO3- secretion. H2 receptor expression was found in duodenal epithelial cells, the enteric nerve plexus, and lymphocytes in Peyer's patch.
  
  
  CONCLUSIONS
  H. pylori VacA inhibits PGE2-stimulated duodenal epithelial HCO3- secretion by a histamine-dependent mechanism. This effect likely contributes to the damaging effect of H. pylori in the duodenal mucosa.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Zunyi Medical College, Zunyi, China. tuobiguang@yahoo.com.cn
authors.forename: Biguang
authors.initials: B
authors.lastname: Tuo
authors.forename: Penghong
authors.initials: P
authors.lastname: Song
authors.forename: Guorong
authors.initials: G
authors.lastname: Wen
authors.forename: Xaver
authors.initials: X
authors.lastname: Sewald
authors.forename: Bettina
authors.initials: B
authors.lastname: Gebert-Vogl
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Michael
authors.initials: M
authors.lastname: Manns
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000633:toxicity*; D001639:Bicarbonates / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004155:Diphenhydramine / Q000494:pharmacology; D004386:Duodenum / Q000166:cytology / Q000378:metabolism*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006632:Histamine / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D011970:Receptors, Histamine H2 / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001639:Bicarbonates; D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2; C074689:VacA protein, Helicobacter pylori; D006632:Histamine; D004155:Diphenhydramine; D015232:Dinoprostone