Bethanechol prevents inhibition of gastric acid secretion by gastric inhibitory polypeptide

Earlier studies of gastric inhibitory polypeptide (GIP) have shown that it is a powerful inhibitor of acid secretion in denervated gastric pouches. Other studies, however, have shown that it is a weak inhibitor in innervated stomach preparations. In this study we evaluated the inhibitory action of GIP in four dogs, each provided with both a vagally denervated (Heidenhain) pouch and a gastric fistula of the innervated stomach. The effect of intravenous infusion of pure porcine GIP (1 microgram X kg-1 X h-1) on pentagastrin dose response was studied with and without background infusion of bethanechol (25 micrograms X kg-1 X h-1). GIP powerfully inhibited pentagastrin-stimulated acid secretion from the Heidenhain pouch but not from the gastric fistula. The maximal inhibition was 76% for the Heidenhain pouch and 29% for the gastric fistula. Despite the attainment of high levels of circulating immunoreactive GIP (greater than 3,000 pg/ml) early after the onset of infusion of the peptide, inhibition occurred relatively late, suggesting that this action of GIP might be mediated by the release of some other substance(s). Background infusion of bethanechol totally abolished the inhibitory action of GIP in both the Heidenhain pouch and gastric fistula.