YM022, A Potent and Selective Gastrin/CCK-B Receptor Antagonist, Inhibits Peptone Meal-Induced Gastric Acid Secretion in Heidenhain Pouch Dogs

We examined the affinity of YM022, a potent andselective gastrin/CCK-B receptor antagonist, for caninegastrin/CCK-B and CCK-A receptors and the effects ofYM022 on secretagogue- and peptone meal-induced acid secretion in the denervated, surgicallyseparated (Heidenhain) canine gastric pouch model incomparison with those of famotidine, an H-receptorantagonist, and atropine. YM022 inhibited the binding of [125I]CCK-8 and[3H]devazepide to canine gastrin/CCK-B andCCK-A receptors, with IC50 values of 0.73 and136 nM, respectively. Intravenous YM022 dose-dependentlyinhibited pentagastrin- and peptone meal-induced acid secretion with ED50 values of0.0261 and 0.0654 mumol/kg, respectively, withoutaffecting histamine- or methacholine-induced acidsecretion. Famotidine inhibited acid secretion inducedby all stimulants, while atropine inhibited the acid secretioninduced by every stimulant except histamine. Theseresults indicated that YM022 is a highly potent andselective antagonist for the canine gastrin/CCK-Breceptor and suppressed pentagastrin- and peptonemeal-induced gastric acid secretion without affectinghistamine- or methacholine-induced acid secretion inHeidenhain pouch dogs.