[Metyrapone effect on gastroprotective action of corticotropin-releasing factor administered centrally against indomethacin-induced gastric injury].

In the present study, we investigated whether corticotropin-releasing factor (CRF) injected into the brain induces protection against indomethacin-caused gastric injury and the role of glucocorticoids in the protection. Gastric injury was caused by indomethacin (35 mg/kg, s.c.) in preliminary (24 h) fasted rats. CRF (10 microgram/rat, i.c.v.) was injected 30 min before administration of indomethacin. The participation of glucocorticoids was studied by metyrapone pretreatment (30 mg/kg, i.p., 30 min before CRF). Pretreatment by metyrapone, the inhibitor of glucocorticoid synthesis was the most suitable approach because of a short-lasting inhibiting effect of the drug. Metyrapone pretreatment allowed us to prevent the acute corticosterone response to CRF and avoid the lasting effects of glucocorticoid deficiency. Intracerebroventricular injection of CRF caused fast increase in plasma corticosterone levels and significantly suppressed the occurrence of gastric erosion induced by indomethacin. Metyrapone administration prevented CRF-induced corticosterone rise and significantly attenuated the protective effect of CRF on the gastric mucosa against indomethacin-produced injury. The results suggest that CRF injected into the brain may induce protection against indomethacin-caused gastric injury through the participation of glucocorticoids.