title: Effects of KB-5492, a new anti-ulcer agent with a selective affinity for the sigma-receptor, on aspirin-induced disruption of the rat gastric mucosal barrier.
abstract: The effect of KB-5492, a new anti-ulcer agent with a selective affinity for the sigma-receptor, on aspirin-induced disruption of the gastric mucosal barrier was studied in rats. Intragastric instillation of aspirin at 200 mg/kg rapidly decreased the gastric transmucosal potential difference (PD) in anesthetized rats. The PD recovered gradually following the removal of aspirin from the instillation solution. Aspirin, administered orally at 200 mg/kg, also reduced the amount of gastric covering mucus and induced a decrease in gastric H+ concentration and an increase in gastric Na+ concentration in pylorus-ligated rats. KB-5492, administered intraduodenally at 200 mg/kg, significantly prevented the aspirin-induced decrease in PD and accelerated the recovery of PD. In addition, KB-5492 at 200 mg/kg significantly prevented the reduction of gastric covering mucus, the decrease in gastric H+ concentration and the increase in gastric Na+ concentration induced by aspirin. These effects were similar to those of 0.01 mg/kg of 16,16-dimethyl prostaglandin E2 (dmPGE2). Teprenone at 200 mg/kg did not show any effect except for the inhibitory effects on the changes in gastric H+ and Na+ concentration. In the histological study, marked reduction of PAS-positive epithelial mucus and the exfoliation of surface epithelial cells were observed in the gastric mucosa exposed to aspirin. KB-5492 and dmPGE2 almost completely prevented the former, whereas both drugs prevented the latter incompletely. These findings indicate that KB-5492 protects the gastric mucosal barrier against the disruption by aspirin, which may be mainly exerted by retention of the gastric covering mucus.
authors.affiliation: Department of Pharmacology, New Drug Research Laboratories, Kanebo Ltd., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Morimoto
authors.forename: K
authors.initials: K
authors.lastname: Shimohara
authors.forename: S
authors.initials: S
authors.lastname: Oshima
authors.forename: H
authors.initials: H
authors.lastname: Hara
authors.forename: T
authors.initials: T
authors.lastname: Sukamoto
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin / Q000009:adverse effects; D004224:Diterpenes / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006859:Hydrogen / Q000032:analysis; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects*; D012964:Sodium / Q000032:analysis
chemical_list: D000897:Anti-Ulcer Agents; D004224:Diterpenes; D010879:Piperazines; D017480:Receptors, sigma; C065167:KB 5492; D006859:Hydrogen; D012964:Sodium; D015064:16,16-Dimethylprostaglandin E2; D001241:Aspirin; C031049:geranylgeranylacetone