title: Possible involvement of host defense mechanism in the suppression of rat acute reflux esophagitis by the particular histamine H2 receptor antagonist lafutidine.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The present results indicate that esophageal host-defense via capsaicin-sensitive afferent nerves may contribute to the therapeutic action of lafutidine.
authors.affiliation: Optimal Medication Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan. moto-nakano@taiho.co.jp
authors.forename: Motoko
authors.initials: M
authors.lastname: Nakano
authors.forename: Hirofusa
authors.initials: H
authors.lastname: Ajioka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Abe
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kiniwa
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000208:Acute Disease; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004942:Esophagitis, Peptic / Q000188:drug therapy* / Q000503:physiopathology; D004947:Esophagus / Q000294:innervation; D006635:Histamine H2 Antagonists / Q000627:therapeutic use*; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology; D010880:Piperidines / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000081:Acetamides; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C076948:lafutidine