ENTEROTOXIC EFFECT OF THE VACUOLATING TOXIN PRODUCED BY HELICOBACTER-PYLORI IN CACO-2 CELLS

Preliminary clinical evidence suggests that Helicobacter pylori may be associated with diarrhea through its vacuolating toxin (VacA), To est ablish whether VacA induces intestinal secretion, epithelial damage, o r both, purified pa-activated VacA was added to Caco-2 cell monolayers mounted in Ussing chambers, and electrical parameters were monitored. Mucosal addition of VacA induced an increase in short circuit current , consistent with enterotoxic effect. The effect was time- and dose-de pendent and saturable. It was not found if the toxin was not pH-activa ted, added to the serosal side, or preheated. In cells preloaded with the Ca2(+) buffering compound BAPTA/AM or with the C1(-) channel inhib itor 5-nitro-2-3-(3-phenylpropylamino)benzoic acid, short circuit curr ent did not change, indicating that VacA induces activation of Ca2(+)- dependent Cl- channels. VacA did not show cytopathic effects, as judge d by tissue resistance. These results support the hypothesis that H. p ylori may be associated with diarrhea through production of VacA.