AIM: To investigate omeprazole-induced transepithelial gastric leak and its effects on the permeability of the peptides bradykinin and oxytocin. METHODS: Rat gastric corpus tissue was isolated and mounted in an Ussing chamber apparatus to evaluate the permeability of 3H-bradykinin, 3H-oxytocin, and 14C-EDTA in the presence or absence of omeprazole. Thin-layer chromatography was performed to identify any metabolic breakdown products of the peptides resulting from permeation through the gastric tissue, and thereby calculate the true flux of the peptide. RESULTS: The flux rate of intact 3H-bradykinin increased substantially after omeprazole addition (109.5%) compared to the DMSO vehicle control (14%). No corresponding change in flux of intact 3H-oxytocin was observed under the same conditions (11.9% and 6.4% in the DMSO- and omeprazole-treated conditions, respectively). After exposure to omeprazole, the flux rate of 14C-EDTA also increased dramatically (122.3%) compared to the DMSO condition (36.3%). CONCLUSION: The omeprazole-induced gastric leak allows for transmucosal permeability to charged molecules as well as non-electrolytes. This induced leak will allow certain peptides to permeate.
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