In celiac disease, one pathway that allows fragments of gliadin protein to get past the intestinal epithelium and subsequently trigger an immune response begins with binding of indigestible gliadin fragments to the chemokine CXC motif receptor 3 (CXCR3) on the luminal side of the intestinal epithelium (see this page).

This complex then initiates a signalling pathway that eventually results in tight junction disassembly and increased intestinal permeability.

Larazotide acetate intervenes in the middle of this pathway by blocking zonulin receptors, thereby preventing tight junction disassembly and associated increase in intestinal permeability.

[3][4] Larazotide acetate is a synthetic peptide based on a Vibrio cholerae enterotoxin called zonula occludens toxin that decreases intestinal permeability.

The eight amino acid sequence in this region was shared with zonulin, an endogenous protein involved in tight junction modulation.