Lipopolysaccharide-induced changes in rat gastric H/K-ATPase expression.

OBJECTIVE

To evaluate lipopolysaccharide (LPS)-induced inhibition of gastric acid secretion.

SUMMARY BACKGROUND DATA

Endotoxemia from LPS inhibits gastric acid secretion by an unknown mechanism. Bacterial overgrowth in the stomach caused by decreased acid secretion could be responsible for nosocomial pneumonia developing in critically ill intensive care unit patients. Because acid secretion is via the H/K-ATPase and the effects of LPS on this enzyme are unknown, we hypothesized that LPS causes inhibition of gastric acid secretion by down-regulating the H/K-ATPase.

METHODS

A rat model to study gastric acid secretion was created. Saline or LPS (0.05-20 mg/kg IP) was given for 1 hour, after which basal acid secretion was determined for 1 hour. Pentagastrin (PG; 10 microg/kg IV) or saline was then given and gastric acid output collected for another 2 hours.

RESULTS

LPS dose dependently inhibited basal and PG stimulated acid secretion. LPS increased alpha- and beta-H/K-ATPase subunit mRNA expression (Northern blot) in the absence of PG compared with saline. In the presence of PG, LPS did not have this effect. Western blot analysis did not show any difference in alpha- or beta-subunit immunoreactivity. Immunofluorescence analysis demonstrated that PG increased staining in the secretory membranes for H/K-ATPase subunits whereas in all LPS-treated rats, it appeared that H/K-ATPase subunits remained within the tubulovesicles. Furthermore, changes in H/K-ATPase mRNA expression may not be related to changes in NF-kappaB activity.

CONCLUSIONS

These data suggest that inhibition of gastric acid secretion by LPS is due to inhibition of H/K-ATPase enzymatic function or changes in cytoskeletal rearrangements in H/K-ATPase subunits rather than by down-regulation of transcriptional or translational events.