Pharmacological profile of a new peptidic gastrin antagonist

Abstract Boc-Trp-Met-Asp-NH 2 was described as the smallest peptidic fragment which presented gastric antisecretory activity. Some pharmacological aspects of a peptide analogue, Boc-Trp-Leu-Asp-NH 2 (Boc-WLD-NH 2 ), were studied on the main biological functions of gastrin. This compound was found to inhibit the binding of gastrin to isolated gastric fundic mucosal cells (IC 50 50 μM). On pentagastrin-induced gastric acid secretion in the rat, a dose-dependent inhibition was observed with and ID 50 of 55 μmol/kg when pentagastrin (1 μg/kg per h) was continuously infused and with an ID 50 of 7.8 μmol/kg when pentagastrin (1 μg/kg) was bolus i.v. injected. Similar inhibition was observed on acid secretion induced by pentagastrin in the isolated rat gastric mucosa (IC 50 100 μM), whereas the tripeptide had no effect when acid output was triggered by histamine. A dose-dependent inhibition with the tripeptide was shown on pentagastrin induced guinea-pig ileum contractions (IC 50 31 μM). The compound had no activity on histamine-stimulated guinea-pig atria (histamine H 2 -receptor). These results suggested some evidence for a selective antigastrin activity.