title: Gastric surface epithelial cell damage induced by restraint and water-immersion stress in rats. Protective effects of 16,16-dimethyl-prostaglandin E2.
abstract: The time course of gastric mucosal surface epithelial cell damage and macroscopically visible lesions in response to restraint and water-immersion stress (22 degrees C) in rats was examined, and the prophylactic effects on it of 16,16-dimethyl-prostaglandin E2 (dmPGE2) were compared with those of papaverine, timoprazole, and atropine. The stress produced surface epithelial cell damage prior to visible lesion, the former increasing in severity with time and reaching a plateau 60 min later, by which time exfoliation of surface epithelial cells was observable along the mucosal folds. In contrast, macroscopically visible lesions appeared 2 h after stress, and severity continued to increase with time. Pretreatment injections (s.c.) of dmPGE2 (3 and 30 micrograms/kg), papaverine (100 mg/kg), and atropine (1 mg/kg) protected the surface cells against stress-induced (1 h) damage, and inhibited visible lesion formation after 4 h stress. Timoprazole (30 mg/kg s.c.) did not protect the surface cells, but did markedly inhibit visible lesion formation. DmPGE2, papaverine, and atropine, but not timoprazole, inhibited stress-induced increases in gastric contractions. DmPGE2, timoprazole, and atropine, but not papaverine, inhibited acid secretion in stress conditions. These results indicated that stress induced damage to the gastric mucosa within 1 h due to increased gastric contractions, and the surface epithelial cell damage developed into macroscopically visible lesions in the presence of acid, and that dmPGE2 protected the surface epithelium against stress-induced damage probably by inhibiting gastric contractions.
authors.affiliation: Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohno
authors.forename: S
authors.initials: S
authors.lastname: Okabe
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000648:ultrastructure; D005769:Gastrointestinal Motility / Q000187:drug effects; D007101:Immersion; D008297:Male; D008855:Microscopy, Electron, Scanning; D009853:Omeprazole / Q000031:analogs & derivatives; D010208:Papaverine / Q000494:pharmacology; D010437:Peptic Ulcer / Q000209:etiology* / Q000517:prevention & control; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000150:complications*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D011459:Prostaglandins E, Synthetic; D001285:Atropine; C038402:timoprazole; D010208:Papaverine; D009853:Omeprazole; D015064:16,16-Dimethylprostaglandin E2