title: [Effects of KSG-504, a new CCK-A receptor antagonist, on gallbladder and gastrointestinal functions].
abstract: We investigated the interaction of KSG-504 with CCK-8- or pentagastrin-induced gallbladder and gastrointestinal responses in vitro and in vivo. KSG-504 (10(-7)-10(-4) M) inhibited CCK-8-induced contractions of both isolated guinea pig gallbladder and rabbit terminal cavity of the bile duct in a concentration-dependent manner. Furthermore, intravenous administration of KSG-504 also dose-dependently inhibited CCK-8-induced gallbladder contraction in anesthetized guinea pigs with an IC50 value of 0.23 mg/kg. In conscious mice, KSG-504 inhibited both CCK-8- and egg yolk-stimulated gallbladder emptying in a dose-dependent manner (IC50: 13.3 and 9.6 mg/kg, respectively). The CCK-8-induced delay of gastric emptying in conscious rats was also antagonized by KSG-504 with an IC50 value of 3.78 mg/kg, i.v., whereas pentagastrin-stimulated gastric acid secretion in anesthetized rats was not affected by KSG-504 at all. KSG-504 (1 mg/kg, i.v.) also inhibited CCK-8-induced duodenal and jejunal contractions in anesthetized rabbits. These results indicate that KSG-504 exerts an antagonistic effect on CCK-A receptors in the gastrointestinal tract, but not on gastrin receptors in the stomach.
authors.affiliation: Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan
authors.forename: Y
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: M
authors.initials: M
authors.lastname: Akahane
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: K
authors.initials: K
authors.lastname: Shinagawa
authors.forename: M
authors.initials: M
authors.lastname: Sugiura
authors.forename: Y
authors.initials: Y
authors.lastname: Ajisawa
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects*; D005704:Gallbladder / Q000187:drug effects*; D016473:Gallbladder Emptying / Q000187:drug effects; D005744:Gastric Acid / Q000378:metabolism; D005746:Gastric Emptying / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D010421:Pentanoic Acids / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D012844:Sincalide / Q000037:antagonists & inhibitors
chemical_list: D009281:Naphthalenes; D010421:Pentanoic Acids; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; C085253:KSG 504; D012844:Sincalide