Helicobacter pylori vacuolating cytotoxin inhibits duodenal bicarbonate secretion by a histamine-dependent mechanism in mice.
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.
Tuo
Biguang
B
Department of Gastroenterology, Affiliated Hospital of Zunyi Medical College, Zunyi, China. tuobiguang@yahoo.com.cn
Song
Penghong
P
Wen
Guorong
G
Sewald
Xaver
X
Gebert-Vogl
Bettina
B
Haas
Rainer
R
Manns
Michael
M
Seidler
Ursula
U
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*
D001426:Bacterial Proteins; D001639:Bicarbonates; D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2; C074689:VacA protein, Helicobacter pylori; D006632:Histamine; D004155:Diphenhydramine; D015232:Dinoprostone