title: Evidence that proglumide and benzotript antagonize secretagogue stimulation of isolated gastric parietal cells.
abstract: 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 X 10(-2) M for proglumide and 1 X 10(-3) M for benzotript. In the case of secretagogue stimulation (1) benzotript slightly affected histamine-induced AP (15% inhibition at 5 X 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 X 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.
mesh_terms: D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D005750:Gastric Juice / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism; D005973:Glutamine / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D011377:Proglumide / Q000494:pharmacology*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism; D011949:Receptors, Cholecystokinin
chemical_list: D001549:Benzamides; D005755:Gastrins; D011956:Receptors, Cell Surface; D011949:Receptors, Cholecystokinin; D000632:Aminopyrine; D005973:Glutamine; D011377:Proglumide; C013841:benzotript