ROLE OF PEPSIN IN THE DEVELOPMENT OF INDOMETHACIN-INDUCED ANTRAL ULCERATION IN THE RAT

Aims: To examine the effects of a pepsin inhibitor, pepstatin-A, a lon g acting H-2-receptor blocker, loxtidine, exogenous pepsin and exogeno us acid against indomethacin-induced antral ulceration in the rat. Res ults: Indomethacin (60 mg/kg s.c.) caused antral ulceration in fasted/ re-fed rats over a period of 4 h. Ulceration was prevented in a dose-d ependent manner by treatment with pepstatin-A (0.1-1 mg.kg hourly) or loxtidine (3 mg/kg) given orally. Acidified methylcellulose (1 mL hour ly per os) enhanced damage and also prevented protection by loxtidine (3 mg/kg per os). The protection by pepstatin-A was not altered by tre atment with acidified methylcellulose but was reversed by treatment wi th a 10-fold excess of pepsin. Conclusion: These studies suggest that mucosal degradation by pepsin, rather than direct damage by luminal ac id, was the major factor in the development of indomethacin-induced an tral ulceration in the rat.