title: Gastric acid secretion in cholecystokinin-1 receptor, -2 receptor, and -1, -2 receptor gene knockout mice.
abstract: Gastrin is important for stimulating acid secretion as well as differentiating gastric mucosal cells via cholecystokinin-2 receptors (CCK-2Rs). In turn, CCK acts preferably via CCK-1R to release somatostatin, and somatostatin has been postulated to exhibit a tonic inhibition of gastrin bioactivity. The present study was designed to examine the hypothesis that CCK-1R and 2R may act in opposite directions in gastric acid secretion. Having generated CCK-1R(-/-), 2R(-/-), and 1R(-/-)2R(-/-) mice, we examined the regulation of gastric acid secretion in four genotypes including wild-type mice. Parietal cells possess histamine receptors, muscarinic receptors, and CCK-2Rs. Since histamine increases cAMP and carbachol increases calcium, the responses of gastric acid secretion to graded doses of histamine, carbachol, and a combination of histamine + carbachol were determined. The sensitivity to histamine did not differ among the four genotypes, while the maximal acid secretion was lower in CCK-2R(-/-) mice than in wild-type mice. In addition, sensitivity to carbachol was impaired in mice without CCK-2R. The interaction of histamine and carbachol was conserved in all genotypes. In conclusion, CCK-2R is necessary to respond to carbachol as well as to produce the maximal acid secretion, while the role of CCK-1R in acid secretion is less important.
authors.affiliation: Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, 173-0015, Japan. kanais@tmig.or.jp
authors.forename: Setsuko
authors.initials: S
authors.lastname: Kanai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hosoya
authors.forename: Saeko
authors.initials: S
authors.lastname: Akimoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Ohta
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Matsui
authors.forename: Soichi
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Funakoshi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Miyasaka