Possible involvement of host defense mechanism in the suppression of rat acute reflux esophagitis by the particular histamine H2 receptor antagonist lafutidine.

Abstract

AIMS:

Gastroesophageal reflux disease is considered to be caused primarily by gastric juice refluxed into the esophagus. Here, we investigated the possible involvement of host defense mechanisms in the development of acute reflux esophagitis using lafutidine, a histamine H(2) receptor antagonist (H(2)RA) with proven gastric mucosal protective effects.

METHODS AND RESULTS:

The ligation of both the pylorus and the forestomach of SD rats under anesthesia caused hemorrhagic lesions in the esophageal mucosa at 6 h. Lesion formation was significantly inhibited by treatment with H(2)RAs, including the conventional H(2)RAs famotidine and cimetidine as well as lafutidine. The maximum suppressive abilities of these agents were similar to that of the proton pump inhibitor lansoprazole. Interestingly, unlike famotidine, lafutidine at low doses significantly suppressed esophagitis without inhibiting gastric acid secretion. Note that neither lafutidine nor famotidine inhibited hexosamine output in gastric juice samples obtained 3 h after ligation. Additionally, the protective effect of lafutidine, but not of famotidine, was partly attenuated by the denervation of capsaicin-sensitive afferent nerves with a large dose of capsaicin.

CONCLUSION:

The present results indicate that esophageal host-defense via capsaicin-sensitive afferent nerves may contribute to the therapeutic action of lafutidine.

• Authors: Motoko Nakano, Hirofusa Ajioka, Masaaki Abe, Mamoru Kiniwa
• Journal: Pharmacology (Pharmacology) Vol. 90 Issue 3-4 Pg. 205-11 ( 2012) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 23038658 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

• Acetamides
• Histamine H2 Antagonists
• Piperidines
• Pyridines
• lafutidine

Topics

• Acetamides (therapeutic use)
• Acute Disease
• Animals
• Dose-Response Relationship, Drug
• Esophagitis, Peptic (drug therapy, physiopathology)
• Esophagus (innervation)
• Histamine H2 Antagonists (therapeutic use)
• Male
• Neurons, Afferent (physiology)
• Piperidines (therapeutic use)
• Pyridines (therapeutic use)
• Rats
• Rats, Sprague-Dawley