Lafutidine, a Protective H2 Receptor Antagonist, Enhances Mucosal Defense in Rat Esophagus
Luminal acid or CO2 induces a hyperemic response in the esophagus, via activation of acid sensors on capsaicin-sensitive afferent nerves (CSAN). Since disruption of the hyperemic response to luminal CO2 acidifies the interstitium of the esophageal mucosa, the hyperemic response may maintain interstitial pH (pHint). We hypothesized that acid-related hyperemia maintains pHint, preventing acid-induced injury in the esophageal mucosa.
We examined the effects of capsaicin (Cap) or lafutidine (Laf), a mucosal protective H2 antagonist, on the regulation of pHint and blood flow in rat esophagus using ratiometric microimaging and laser-Doppler measurements of the lower esophageal mucosa of living rats. The esophagus was topically superfused with pH 7.0 buffer, or a pH 1.0 or pH 1.0 + pepsin (1 mg/ml) solution with or without Laf.
Cap (30 or 100 µM) or Laf (0.1 or 1 mM) dose-dependently increased blood flow, accompanied by increased pHint. The pH 1.0 solution increased blood flow without pHint change, whereas Laf (1 mM) increased blood flow and pHint during acid exposure. The effects of Laf were abolished by ablation of CSAN. Perfusion of the acidified pepsin solution gradually decreased pHint, inhibited by Laf perfusion.
Activation of CSAN by Laf with or without acid, accompanied by hyperemia, increased pHint, preventing acidified pepsin-induced interstitial acidification. Stimulation of the capsaicin pathway with compounds such as Laf enhances mucosal protection from acid-related injury in the upper gastrointestinal tract.
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- Lafutidine, a Protective H2 Receptor Antagonist, Enhances Mucosal Defense in Rat Esophagus
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Digestive Diseases and Sciences
Volume 55, Issue 11 , pp 3063-3069
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- Print ISSN
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- Springer US
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- Esophageal blood flow
- Interstitial pH
- Capsaicin-sensitive afferent nerves
- Interstitial acidification
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- Author Affiliations
- 1. Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, CA, 90073, USA
- 2. Department of Medicine, School of Medicine, University of California Los Angeles, Los Angeles, CA, 90073, USA
- 3. Brentwood Biomedical Research Institute, West Los Angeles VA Medical Center, Bldg. 114, Suite 217, 11301 Wilshire Blvd., Los Angeles, CA, 90073, USA