Irritative and protective activity of mild irritants in rat stomach

Exposure of the stomach for 30 min to acidified sodium taurocholate (TC) (1-20 mM) or sodium salicylate (SA) (10-80 mM) caused a reduction of transmucosal PD and an increase of luminal pH in anesthetized rats, in a concentration-related manner. Acidified aspirin (ASA) (10-80 mM) reduced PD in the same manner, without significant effect on pH. Histologically, these agents similarly produced damage to the surface cells. After a 30-min exposure to either 20 mM TC or 40 mM SA, acid secretion ceased and bicarbonate (0.5-1 mumol/10 min) appeared in the lumen, whereas acid secretion persisted in the stomach exposed to 40 mM ASA. However, under cimetidine infusion (8 mg/kg/hr) these agents produced similar degrees of luminal alkalinization (approximately 1 mumol/10 min). Pretreatment with indomethacin (5 mg/kg, subcutaneously) significantly inhibited the increase of pH seen after exposure to 20 mM TC, but had no effect on the increase of pH caused by 40 mM SA. Concurrent administration of 16,16-dmPGE2 (3 micrograms/kg, subcutaneously) significantly antagonized the effect of indomethacin in the stomach exposed to 20 mM TC and even increased the pH in the stomach exposed to 40 mM ASA. After a 3-hr exposure to these agents, there was macroscopically apparent damage only in the stomach exposed to ASA, although the PD was similarly reduced in response to either agent. The levels of PGE2 in the corpus mucosa were significantly increased in stomachs exposed to 20 mM TC and 40 mM SA, but decreased in those exposed to 40 mM ASA.(ABSTRACT TRUNCATED AT 250 WORDS)