Effects of 16,16-dimethyl-prostaglandin E2 on ammonia- and ethanol-induced mucosal lesions in the rat.

The effect of necrotizing agents, such as ammonia and ethanol, on the gastric mucosa was compared. Intragastric administration of ammonia (0.6-1.0%) and ethanol (60-100%) produced hemorrhagic necrosis of gastric mucosa in a concentration-dependent manner. In the anesthetized rat, the macroscopic lesions induced by ethanol were significantly inhibited by pretreatment with 3 or 10 micrograms/kg of 16,16-dmPGE2, but the lesions induced by ammonia were not inhibited by either 3 or 10 micrograms/kg of 16,16-dmPGE2 in the anesthetized rat. The decrease of gastric transmucosal potential difference and mucosal blood flow produced by ethanol (100%) were significantly attenuated by 16,16-dmPGE2; however, those produced by ammonia (1%) were not inhibited by 16,16-dmPGE2 in the anesthetized rat. In conscious rats, ammonia-induced lesions were not inhibited by pretreatment with 3 micrograms/kg of 16,16-dmPGE2 but they were significantly reduced by the pretreatment of 10 micrograms/kg of 16,16-dmPGE2. These results show that 16,16-dmPGE2 afforded little protection against ammonia-induced gastric lesions in the anesthetized rat and suggest that a different mechanism is involved in the development of gastric mucosal lesions between those induced by ethanol and those induced by ammonia.