title: YM022, a potent and selective gastrin/CCK-B receptor antagonist, inhibits peptone meal-induced gastric acid secretion in Heidenhain pouch dogs.
abstract: We examined the affinity of YM022, a potent and selective gastrin/CCK-B receptor antagonist, for canine gastrin/CCK-B and CCK-A receptors and the effects of YM022 on secretagogue- and peptone meal-induced acid secretion in the denervated, surgically separated (Heidenhain) canine gastric pouch model in comparison with those of famotidine, an H2-receptor antagonist, and atropine. YM022 inhibited the binding of [(125)I]CCK-8 and [(3)H]devazepide to canine gastrin/CCK-B and CCK-A receptors, with IC50 values of 0.73 and 136 nM, respectively. Intravenous YM022 dose-dependently inhibited pentagastrin- and peptone meal-induced acid secretion with ED50 values of 0.0261 and 0.0654 micromol/kg, respectively, without affecting histamine- or methacholine-induced acid secretion. Famotidine inhibited acid secretion induced by all stimulants, while atropine inhibited the acid secretion induced by every stimulant except histamine. These results indicated that YM022 is a highly potent and selective antagonist for the canine gastrin/CCK-B receptor and suppressed pentagastrin- and peptone meal-induced gastric acid secretion without affecting histamine- or methacholine-induced acid secretion in Heidenhain pouch dogs.
authors.affiliation: Institute For Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba city, Ibaraki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yuki
authors.forename: A
authors.initials: A
authors.lastname: Nishida
authors.forename: A
authors.initials: A
authors.lastname: Miyake
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Akuzawa
authors.forename: Y
authors.initials: Y
authors.lastname: Takinami
authors.forename: Y
authors.initials: Y
authors.lastname: Takemoto
authors.forename: K
authors.initials: K
authors.lastname: Miyata
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D001570:Benzodiazepinones / Q000378:metabolism / Q000494:pharmacology; D020109:Devazepide; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004435:Eating; D015738:Famotidine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology; D010461:Peptones / Q000494:pharmacology*; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000378:metabolism; D013270:Stomach / Q000502:physiology
chemical_list: D001570:Benzodiazepinones; D006635:Histamine H2 Antagonists; D006727:Hormone Antagonists; D018727:Muscarinic Antagonists; D010461:Peptones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D016210:Methacholine Chloride; D001569:Benzodiazepines; C087260:YM 022; C058121:L 365260; D015738:Famotidine; D001285:Atropine; D006632:Histamine; D010418:Pentagastrin; D020109:Devazepide; D012844:Sincalide