title: Transmucosal gastric leak induced by proton pump inhibitors.
abstract: Despite their remarkable safety profile and lack of clinical side effects, proton pump inhibitors (PPIs) induce a transmucosal gastric leak to non-electrolyte probes of various sizes. The ex vivo addition of PPIs to isolated rat gastric corpus increases transmucosal permeability in a dose-dependent manner, which corresponds with PPIs' dose-dependent inhibition of acid secretion. Upon the addition of omeprazole, lansoprazole, or esomeprazole, a small decrease in transepithelial resistance and the concomitant stimulation of short circuit current was observed. Additionally, transepithelial flux of (14)C-[D]-mannitol (MW 182.17) across the gastric mucosa increased by a mean of 68% immediately following the addition of 200 microM omeprazole. This flux increase was bidirectional. Omeprazole also increased the paracellular permeability to larger radiolabeled probes, including (14)C-sucrose (MW 342.3) and (14)C-polyethylene glycol (MW 4,000) by 118% and 350%, respectively. However, the flux of still larger probes, 10,000 and 70,000 MW dextrans, was not increased. Because PPIs are so widely used and are assumed to be innocuous, this transmucosal gastric leak must be further investigated, as it may carry considerable biomedical implications.
authors.affiliation: Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Murray
authors.forename: Melissa
authors.initials: M
authors.lastname: Gabello
authors.forename: David S
authors.initials: DS
authors.lastname: Rudolph
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Farrell
authors.forename: Melissa
authors.initials: M
authors.lastname: Morgan
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Martin
authors.forename: James C
authors.initials: JC
authors.lastname: Underwood
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Valenzano
authors.forename: James M
authors.initials: JM
authors.lastname: Mullin
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000009:adverse effects; D000818:Animals; D000897:Anti-Ulcer Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects; D064098:Esomeprazole; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D064747:Lansoprazole; D008297:Male; D009853:Omeprazole / Q000009:adverse effects*; D010539:Permeability / Q000187:drug effects; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D009853:Omeprazole; D064098:Esomeprazole