Pharmacological profile of a new peptidic gastrin antagonist.
Boc-Trp-Met-Asp-NH2 was described as the smallest peptidic fragment which presented gastric antisecretory activity. Some pharmacological aspects of a peptide analogue, Boc-Trp-Leu-Asp-NH2 (Boc-WLD-NH2), 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 (IC50 50 microM). On pentagastrin-induced gastric acid secretion in the rat, a dose-dependent inhibition was observed with an ID50 of 55 mumol/kg when pentagastrin (1 microgram/kg per h) was continuously infused and with an ID50 of 7.8 mumol/kg when pentagastrin (1 microgram/kg) was bolus i.v. injected. Similar inhibition was observed on acid secretion induced by pentagastrin in the isolated rat gastric mucosa (IC50 100 microM), 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 (IC50 31 microM). The compound had no activity on histamine-stimulated guinea-pig atria (histamine H2-receptor). These results suggest some evidence for a selective antigastrin activity.
D000818:Animals; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D005755:Gastrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats
D005755:Gastrins; D009842:Oligopeptides; D006632:Histamine; C050801:tert-butyloxycarbonyl-tryptophyl-leucyl-asparagine; D010418:Pentagastrin