Abstract
Stress may contribute to the development of gastric ulcer disease. The results of our previous investigations suggest that glucocorticoids released during acute stress act as gastroprotective hormones, and not as ulcerogenic agents as has been generally accepted for a long time. In this study, we investigated whether corticotropin-releasing factor (CRF) may protect the gastric mucosa against stress-induced gastric injury through involvement of glucocorticoids. Intraperitoneal administration of CRF (1.25 μg/kg, 30 min before stress) markedly increased plasma corticosterone level (at 15 and 30 min after the administration) and significantly suppressed the occurrence of gastric erosion induced by 3-h cold-restraint stress (at 10°C) in conscious rats. To test the participation of corticosterone in the gastroprotective effect of exogenous CRF, two approaches were used: pretreatment by the inhibitor of glucocorticoid synthesis, metyrapone (30 mg/kg, i.p.) and the antagonist of glucocorticoid receptors RU-38486 (20 mg/kg, i.p.). Metyrapone injected shortly before CRF administration caused a fast inhibition of CRF-induced corticosterone response and reversed the protective effect of CRF on the gastric mucosa against the stress-induced erosion. The gastroprotective effect of CRF was also attenuated by the pretreatment rats with glucocorticoid receptor antagonist RU-38486. The results suggest that exogenous CRF may protect the gastric mucosa against stress-induced gastric injury through involvement of glucocorticoids.