Inhibitors of acid secretion can benefit gastric wound repair independent of luminal pH effects on the site of damage
- 1Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- 2Department of Physiology, University of Liverpool, Liverpool, UK
- Correspondence to Dr Marshall H Montrose, Department of Molecular and Cellular Physiology, University of Cincinnati, MSB 4207, 231 Albert Sabin Way, Cincinnati, OH 45267, USA;
Contributors ESD performed, analysed and interpreted the experiments, and drafted the manuscript. EA performed, analysed and interpreted the experiments, and edited the manuscript. SK performed and analysed the experiments. AV provided unique reagents and analysed the results. MHM contributed to the study concept and funding, and helped with the analysis and interpretation of results and manuscript editing.
- Revised 6 September 2011
- Accepted 8 September 2011
- Published Online First 13 October 2011
Background and aims The authors' goal was to measure pH at the gastric surface (pHo) to understand how acid secretion affects the repair of microscopic injury to the gastric epithelium.
Methods Microscopic gastric damage was induced by laser light, during confocal/two-photon imaging of pH-sensitive dyes (Cl-NERF, BCECF) that were superfused over the mucosal surface of the exposed gastric corpus of anaesthetised mice. The progression of repair was measured in parallel with pHo. Experimental conditions included varying pH of luminal superfusates, and using omeprazole (60 mg/kg ip) or famotidine (30 mg/kg ip) to inhibit acid secretion.
Results Similar rates of epithelial repair and resting pHo values (∼pH 4) were reported in the presence of luminal pH 3 or pH 5. Epithelial repair was unreliable at luminal pH 2 and pHo was lower (2.5±0.2, P <0.05 vs pH 3). Epithelial repair was slower at luminal pH 7 and pHo was higher (6.4±0.1, P<0.001). In all conditions, pHo increased adjacent to damage. At luminal pH 3 or pH 7, omeprazole reduced maximal damage size and accelerated epithelial repair, although only at pH 3 did omeprazole further increase surface pH above the level caused by imposed damage. At luminal pH 7, famotidine also reduced maximal damage size and accelerated epithelial repair. Neither famotidine nor omeprazole raised plasma gastrin levels during the time course of the experiments.
Conclusions Epithelial repair in vivo is affected by luminal pH variation, but the beneficial effects of acutely blocking acid secretion extend beyond simply raising luminal and/or surface pH.
- Laser scanning confocal microscopy
- two-photon microscopy
- histamine antagonist
- proton-pump inhibitor
- gastric physiology
- gastric epithelial cell function
- gastric wound repair
- gastric mucosal barrier
- intestinal transport
Funding National Institutes of Health grant R01-DK54940.
Competing interests None.
Ethics approval This study was approved by the institutional animal care and use committee of the University of Cincinnati.
Provenance and peer review Not commissioned; externally peer reviewed.