Lipopolysaccharide-Induced Changes in Rat Gastric H/K-ATPase Expression

Kenneth S. Helmer, Sonlee D. West, Ron Vilela, Lily Chang, Yan Cui, Bruce C. Kone, David W. Mercer

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 μg/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 α- and β-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 α- or β-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-κB 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.

Original languageEnglish (US)
Pages (from-to)501-509
Number of pages9
JournalAnnals of surgery
Volume239
Issue number4
DOIs
StatePublished - Apr 2004

ASJC Scopus subject areas

  • Surgery

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