Digestive Diseases and Sciences

, Volume 49, Issue 11–12, pp 1845–1852 | Cite as

A Role for CagA/VacA in Helicobacter pylori Inhibition of Murine Duodenal Mucosal Bicarbonate Secretion

  • Bi-Guang Tuo
  • Zachary M. Sellers
  • Anders J. Smith
  • Kim E. Barrett
  • Jon I. Isenberg
  • Hui DongEmail author


Duodenal mucosal bicarbonate secretion is diminished in patients with Helicobacter pylori (HP)-associated duodenal ulcer disease. We examined whether HP water extracts inhibit murine duodenal mucosal bicarbonate secretion {in vitro}, and the mechanisms involved. Murine duodenal mucosae were mounted in Ussing chambers. Short-circuit current and bicarbonate secretion was measured. CagA/VacA-positive HP water extract (HPWE+/plus;) markedly inhibited PGE2-, carbachol-, or the calcium ionophore A23187-stimulated bicarbonate secretion in a dose-dependent manner. While 3-isobutyl-1-methylxanthine-stimulated bicarbonate secretion was not affected by HPWE+/plus;, HPWE+/plus; did diminish forskolin-stimulated bicarbonate secretion. HPWE+/plus; markedly diminished PGE2-induced increases in duodenal mucosal cAMP. CagA/VacA of HP decreases Ca2+-mediated bicarbonate secretiondownstream of increases in intracellular Ca2+. Dimunition of PGE2-stimulated bicarbonate secretion occurs, in part, by inhibition of adenylate cyclase, which leads to decreased cAMP levels. The ability of virulent HP strains to inhibit duodenal bicarbonate secretion through multiple intracellular pathways likely contributes to the pathogenesis of HP-associated duodenal ulcer disease.

Helicobacter pylori CagA VacA duodenal bicarbonate secretion 


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Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Bi-Guang Tuo
    • 1
    • 2
  • Zachary M. Sellers
    • 1
  • Anders J. Smith
    • 1
  • Kim E. Barrett
    • 1
  • Jon I. Isenberg
    • 1
  • Hui Dong
    • 1
    Email author
  1. 1.Division of Gastroenterology, Department of MedicineUniversity of California, San Diego, School of MedicineSan DiegoUSA
  2. 2.Department of Gastroenterology and Hepatology Hannover Medical SchoolHannoverGermany

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