Evidence that proglumide and benzotript antagonize secretagogue stimulation of isolated gastric parietal cells

Proglumide has been shown to be an in vivo inhibitor of secretagogue-stimulated gastric acid secretion. In the present study, we have examined the ability of proglumide and benzotript, a new tryptophan derivative, to inhibit acid output from isolated gastric fundic parietal cells from rabbit. As measured with the [ 14C]aminopyrine (AP) accumulation method as an index of acid secretion, the two drugs inhibited basal AP with IC-50 values of 1 × 10 −2 M for proglumide and 1 × 10 −3 M for benzotript. In the case of secretagogue stimulation (1) benzotript slightly affected histamine-induced AP (15% inhibition at 5 × 10 −3 M ), proglumide did not; (2) both proglumide and benzotript inhibited in a non-competitive manner acetylcholine-induced AP; (3) these isolated cells were sensitive to gastrin and the dose-response curve for the stimulant was biphasic (maximum for 1 × 10 −9 M ), suggesting a desensitization mechanism. Proglumide and benzotript competitively inhibited both [ 125I]gastrin binding to its receptor sites and gastrin-induced AP, suggesting they are members of a class of gastrin-receptor antagonists. But, this suggestion cannot exclude other post-receptorial mechanisms involved in the acid output from parietal cells.