Some profiles of transmucosal potential difference in rat stomach determined in situ with special reference to effects of timoprazole, a H+,K+-ATPase inhibitor.

Gastric transmucosal potential difference (PD) is referred to an index of function and integrity of the mucosa. The features of gastric PD were studied in association with gastric acid secretion. The gastric PD was measured at the forestomach, glandular portion and pylorus in the rat in in situ preparations. Secretagogues such as bethanechol (BeCh, 50 micrograms/kg, i.v.), tetragastrin (TG, 30 micrograms/kg, i.v.), and histamine (Hist, 10 mg/kg, s.c.) produced a decrease in PD at the three regions of the stomach. These PD reductions did not occur with the combined treatment with timoprazole (30 mg/kg, i.d.); a marked increase in PD was noted, especially, in the case of Hist plus timoprazole. Similarly, BeCh induced PD decrease was antagonized by atropine (30 micrograms/kg, i.v.) and Hist induced PD decrease was attenuated by cimetidine (10 mg/kg, i.v.), while TG induced PD decrease was not affected by either of them. Of the antisecretory drugs, only cimetidine produced an increase in basal PD, probably via a mechanism unrelated to acid secretion. These results suggest that the PD decrease by each secretagogue seen at oxyntic and non-oxyntic gland regions of the stomach primarily originates from secretory activation of the parietal cells and that its action on function unrelated to acid secretion also exerts a minor influence on gastric PD.