[Gastroprotective action of corticotropin-releasing factor (CRF): involvement of glucocorticoids and CRF receptors type 2].

ABSTRACT

The stress response involves the activation of two corticotropin-releasing factor (CRF) receptors types 1 and 2. The pituitary type 1 CRF receptors represent the primary receptors to activate the hypothalamic-pituitary-adrenocortical axis and, consequently, glucocorticoid production. Exogenous CRF induces an increase in glucocorticoid production and may protect the gastric mucosa against stress-induced injury. Here we examined contribution of glucocorticoids and CRF receptors type 2 to gastroprotective effect of exogenous CRF. Gastric injury was induced by 3 him-mobilization (at 10 degrees C) in conscious rats or 3.5 h gastric ischemia-reperfusion in anaesthetized rats. Intraperitoneal administration of CRF at the doses of 1.25 or 2.5 Mg/kg increased plasma corticosterone levels and suppressed the occurrence of gastric erosion induced by each stimulus. Metyrapone injected before CRF caused an inhibition of CRF-induced corticosterone response and prevented the protective effect of CRF on the gastric mucosa against erosion caused by immobilization (at 10 degrees C). However, metyrapone injection did not influence the protective effect of CRF on the gastric mucosa against ischemia-reperfusion-induced lesion. The protective effect of CRF on the gastric mucosa against ischemia-reperfusion-induced lesion was prevented by the nonselective CRF receptor antagonist astressin and selective type 2 CRF receptor antagonist astressin2-B. The results obtained suggest that exogenous CRF may protect the gastric mucosa against injury through involvement of glucocorticoids and also through CRF receptors type 2.