Mucosal ulceration in isolated amphibian stomachs in vitro. Roles of nutrient HC03- and endogenous prostaglandins

We examined the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on mucosal ulceration in isolated bullfrog stomachs and investigated the roles of endogenous prostaglandins (PGs) and nutrient HCO3- in the mucosal protection in vitro. Gastric sacs were prepared by separation from the muscle layer and incubation for 1-8 h in HCO3--Ringer's solution gassed with 95% 02/5% CO2 or PO3(-)4-Ringer's solution gassed with 100% 02 in the presence of histamine (1 x 10(-4) M). Under these conditions, multiple ulcers developed in the mucosa only when the gastric sacs were incubated in HCO3--free nutrient solution; both the number and severity of ulcers increased with time and reached a maximum after 6 h of incubation. Luminal pH was decreased because of stimulation of acid secretion by histamine, irrespective of whether the mucosa was bathed in Ringer's solution with or without HCO3-, while gastric potential difference was reduced only in the mucosa bathed in HCO3--free nutrient solution. 16,16-Dimethyl PGE2 added to the nutrient side significantly reduced the number of ulcers developed in the mucosa bathed in HCO3--free nutrient solution. In contrast, indomethacin and aspirin, but not salicylate, caused ulceration even in the mucosa bathed in HCO3--nutrient solution. Histamine-induced acid secretion was reduced by 16,16-dimethyl PGE2 but not affected by these NSAIDs. In conclusion, ulceration of the isolated gastric mucosa in the presence of acid depends upon either a deficiency of endogenous PGs or a lack of nutrient HCO3-/CO2.