The enterotoxic effect of zonula occludens toxin on rabbit small intestine involves the paracellular pathway

Background & Aims: Zonula occludens toxin is a novel toxin elaborated by Vibrio cholerae that modulates intestinal tight junctions. The aim of this study was to establish whether the permeabilizing effect of the toxin leads to intestinal secretion. Methods: Rabbit intestine was mounted in Ussing chambers and exposed to increasing concentrations of purified toxin. The tissues were also fixed, exposed to zonula occludens toxin, and processed for fluorescence microscopy to determine the distribution of the toxin receptor within the intestine. Then purified toxin was simultaneously perfused in three distinct rabbit intestinal segments in vivo, and water and electrolyte absorption were measured. Results: Zonula occludens toxin induced a time- and dose-dependent decrease of tissue resistance starting at a toxin concentration of 1.1 x 10(-13) mol/L. When tested in vivo, the toxin induced a secretion of water and chloride and the passage of polyethylene glycol 4000 in the bloodstream. Both the in vitro and in vivo effects of the toxin were observed only in the small intestine but not in the colon and paralleled the distribution of the toxin receptor within the intestine. Conclusions: The intestinal secretion induced by zonula occludens toxin follows the opening of tight junctions caused by the toxin, possibly representing a novel mechanism of intestinal secretion.