Leukocyte depletion and ONO-5046, a specific inhibitor of granulocyte elastase, prevent a stress-induced decrease in gastric prostaglandin I2 in rats.
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.
Harada
N
N
Department of Emergency and Critical Care Medicine, School of Medicine, Fukuoka University, Japan.
Okajima
K
K
Murakami
K
K
Uchiba
M
M
Tanaka
K
K
Okabe
H
H
Takatsuki
K
K
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*
D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; C069195:sivelestat; D019272:Leukocyte Elastase; D016285:Iloprost; D005998:Glycine