Cytoprotective effect of centrally administered corticotropin-releasing factor on stress-induced gastric mucosal lesions

Abstract

The effect of intracisternal (ic) injection of ovine corticotropin-releasing factor (CRF) on the development of gastric mucosal lesions induced by cold-plus-restraint stress was studied in rats. Adult male Wistar rats were fasted for 24h. Following is injection of CRF or saline, they were restrained in wire mesh and placed supine in a cold room at 4°C for 3h. After the 3-h stress, rats were killed by decapitation. Gastric mucosa was exposed and mucosal lesions were assessed. This regimen consistently produced mucosal lesions in control rats. Ic injection of 15 μg CRF significantly inhibited the development of gastric mucosal lesions, while the effect was not reproduced by intraperitoneal injection of 45μg CRF. Ic injection of 5μg somatostatin-28 (SS-28) alone did not influence the development of gastric mucosal lesions in this model. When SS-28 was coadministered with CRF centrally, the cytoprotective effect of CRF in this model was completely abolished. The development of gastric mucosal lesions following the stress was prevented by the prior administration of chlorisondamine, a ganglion blocker or atropine, an antagonist of muscarinic cholinergic receptor, but it was not affected by the injection of phenoxybenzamine, an α-adrenergic blocker. When cold-plus-restraint rats were pretreated with indomethacin, an inhibitor of prostaglandin synthesis, the cytoprotective effect of centrally administered CRF was abolished.The results show that centrally administered CRF exerted a cytoprotective effect on stress-induced gastric mucosal lesions and the effect was counteracted by somatostatin-28. The action of CRF appears to be mediated centrally by inhibiting the activity of muscarinic cholinergic fibers, while locally, it requires intact prostaglandin synthesis.