ROLE OF POLYAMINES AND PROSTAGLANDINS IN GASTROPROTECTIVE ACTION OF EPIDERMAL GROWTH-FACTOR AGAINST ETHANOL INJURY

Epidermal growth factor (EGF) exhibits its gastroprotective action against a variety of irritants and ulcerogens and plays an important role in healing of acute and chronic gastroduodenal ulcerations, but the mechanisms of these effects are not known. The present study was undertaken to determine whether polyamines (such as spermine or putrescine) and prostaglandins (PGs), which also show protective properties, contribute to the gastroprotective effect of EGF against ethanol injury in rats. It was found that both EGF and polyamines significantly and dose-dependently prevented the formation of gastric lesions induced by absolute ethanol, the effect being similar to that obtained with 16,16-dimethylprostaglandin E2. Pretreatment with indomethacin failed to affect the gastroprotective action of EGF and polyamines, suggesting that endogenous PGs may not play any major role in this protection. Our finding that the protective effect of EGF can be abolished by pretreatment with DFMO, an inhibitor of the polyamine biosynthetic pathway, suggests that gastroprotection by EGF is due, at least in part, to stimulation of biosynthesis of protective polyamines.