Omeprazole induces gastric transmucosal permeability to the peptide bradykinin.
OBJECTIVE
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 (3)H-bradykinin, (3)H-oxytocin, and (14)C-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 (3)H-bradykinin increased substantially after omeprazole addition (109.5%) compared to the DMSO vehicle control (14%). No corresponding change in flux of intact (3)H-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 (14)C-EDTA also increased dramatically (122.3%) compared to the DMSO condition (36.3%).


CONCLUSIONS
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.
Gabello
Melissa
M
Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096, USA.
Valenzano
Mary Carmen
MC
Zurbach
E Peter
EP
Mullin
James M
JM
D000818:Animals; D001692:Biological Transport; D001920:Bradykinin / Q000378:metabolism*; D004492:Edetic Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010121:Oxytocin / Q000378:metabolism; D010539:Permeability; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
D054328:Proton Pump Inhibitors; D010121:Oxytocin; D004492:Edetic Acid; D009853:Omeprazole; D001920:Bradykinin