Brief Article
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World J Gastroenterol. Mar 7, 2010; 16(9): 1097-1103
Published online Mar 7, 2010. doi: 10.3748/wjg.v16.i9.1097
Omeprazole induces gastric transmucosal permeability to the peptide bradykinin
Melissa Gabello, Mary Carmen Valenzano, E Peter Zurbach, James M Mullin
Melissa Gabello, Mary Carmen Valenzano, James M Mullin, Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, United States
Melissa Gabello, Department of Biology, Saint Joseph’s University, 5600 City Avenue, Philadelphia, PA 19131, United States
E Peter Zurbach, Department of Chemistry, Saint Joseph’s University, 5600 City Avenue, Philadelphia, PA 19131, United States
James M Mullin, Division of Gastroenterology, Lankenau Hospital, 100 Lancaster Avenue, Wynnewood, PA 19096, United States
Author contributions: Gabello M and Valenzano MC both performed the research studies; Mullin JM designed the research studies; Zurbach EP assisted with interpretation of results and guidance in EDTA structure and ionic charge considerations; this work was a portion of the M.S. thesis of Gabello M; Gabello M and Mullin JM jointly wrote this paper.
Correspondence to: James M Mullin, PhD, Professor, Lankenau Institute for Medical Research; Director of Research, Division of Gastroenterology, Lankenau Hospital, 100 Lancaster Avenue, Wynnewood, PA 19096, United States. mullinj@mlhs.org
Telephone: +1-484-4762708 Fax: +1-484-4762205
Received: August 26, 2009
Revised: November 26, 2009
Accepted: December 3, 2009
Published online: March 7, 2010
Abstract

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.

Keywords: Proton pump inhibitor, Paracellular, Drug delivery, Tight junction, Transepithelial