Isolated gastric mucosa: an early approach to the study of the mechanism of action of gastric antisecretory agents.

The results of five different experiments carried out on isolated gastric mucosa were evaluated. These were: 1) Effects of antisecretory agents on (H+) and (K+) in a histamine-stimulated (4 x 10(-5)M) preparation. 2) Effects on (H+) in a preparation stimulated by dibutyryl cyclic adenosine monophosphate (dbcAMP) (6 x 10(-4)M). 3) Reversal by antipyrine (3 x 10(-2)M) of the antacid effect of antisecretory agents in a histamine-stimulated (4 x 10(-5)M) preparation. 4) Effects on the antacid activity of antisecretory agents of a pretreatment with 2-mercaptoethanol (2-ME) (2 x 10(-2)M) in a histamine-stimulated (4 x 10(-5] preparation. 5) Reversal by intraluminal increase of (K+) (up to 144.3 mM) of the antacid effect of antisecretory agents in a histamine-stimulated (4 x 10(-5)M) preparation. The technique and its application to a series of known antisecretory agents--cimetidine, ranitidine, timoprazole and omeprazole--and to other substances with antisecretory activity such as sodium thiocyanate, verapamil, trimipramine and imipramine, is described. In order to illustrate the activity of the aforementioned substances in the more classic tests of antisecretory activity, an in vivo test of inhibition of gastric secretion in pylorus-ligated rats and the in vitro tests of H2-receptor blocking activity (isolated guinea-pig atrium), anticholinergic activity (isolated guinea-pig ileum) and carbonic anhydrase (canine blood) were included. The results show that substances with different mechanisms of action behave differently in the five experiments in isolated gastric mucosa described, and these may thus be considered useful for the study of the mechanism of action of gastric antisecretory agents.