[GASTROPROTECTIVE EFFECT OF CORTICOTROPIN-RELEASING FACTOR IN STREPTOZOTOCIN-INDUCED DIABETIC RATS].

Abstract

The results of our previous studies suggest that corticotropin-releasing factor (CRF) protects the gastric mucosa of rats against stress- and indomethacin-induced gastric injury. In the present study, we investigated whether CRF may protect gastric mucosa against indomethacin-induced gastric injury on diabetic rats. Diabetes was induced by streptozotocin (70 mg/kg) 14 days before indomethacin injection. CRF (2.5 |xg/kg) and CRF receptor antagonists were injected 15 min before indomethacin. The diabetes development resulted in the aggravation of gastric mucosal erosion produced by indomethacin. Intraperitoneal CRF administration caused pronounced gastropro-tective action in control as well as diabetic rats that resulted in significant attenuation of indomethacin-induced gastric erosion. Nonselective antagonist CRF receptors astressin as well as selective antagonists of CRF1 and CRF2 receptors (NBI 27914, 10 mg/kg or astressin2-B, 50 |xg/kg, respectively) aggravated ulcerogenic effect of indomethacin in diabetic rats. The results obtained suggest that exogenous and endogenous CRF may protect the gastric mucosa of diabetic rats against indomethacin-induced injury through CRF1 and CRF2 receptors.