title: Leukocyte depletion and ONO-5046, a specific inhibitor of granulocyte elastase, prevent a stress-induced decrease in gastric prostaglandin I2 in rats.
abstract: To examine whether activated leukocytes may impair the endothelial production of prostaglandin (PG) I2, an important cytoprotective agent in gastric mucosa, we investigated the effects of leukocyte depletion and ONO-5046, a specific inhibitor of granulocyte elastase, on the gastric level of this prostaglandin and gastric mucosal injury in rats subjected to water-immersion restraint stress (WIR). Gastric 6-keto-PGF1 alpha was increased after 30 min of WIR, followed by a decrease to below baseline after 6 h of stress. Gastric levels of 6-keto-PGF1 alpha in leukopenic animals or animals pretreated with ONO-5046 after 1 h of stress were significantly higher than those of controls, levels after 6 h of stress were not lower than those preceding stress. Leukocytopenia or ONO-5046 significantly inhibited WIR-induced gastric mucosa lesion formation. Iloprost, a stable derivative of PGI2, prevented stress-induced lesions. These results suggest that activated leukocytes may play an important role in stress-induced gastric mucosal lesion formation by inhibiting production of PGI2.
authors.affiliation: Department of Emergency and Critical Care Medicine, School of Medicine, Fukuoka University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Harada
authors.forename: K
authors.initials: K
authors.lastname: Okajima
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Uchiba
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Okabe
authors.forename: K
authors.initials: K
authors.lastname: Takatsuki
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D011464:Epoprostenol / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016285:Iloprost / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D007962:Leukocytes / Q000502:physiology*; D007970:Leukopenia; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013312:Stress, Physiological / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; C069195:sivelestat; D019272:Leukocyte Elastase; D016285:Iloprost; D005998:Glycine