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.
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
K
K
Takeuchi
H
H
Miyake
Okabe
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D011453:Prostaglandins / Q000502:physiology*; D011892:Rana catesbeiana; D013276:Stomach Ulcer / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control
D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D011453:Prostaglandins; D015064:16,16-Dimethylprostaglandin E2