BACKGROUND & AIMS: Gastrin and cholecystokinin (CCK) are gut-brain peptides, with multiple functions in the gastrointestinal tract mediated through CCK-B-gastrin and CCK-A receptors. The receptor localization is, however, not well established in humans. The aim of this study was to investigate the distribution and pharmacological characteristics of CCK-A and CCK-B receptors in the human upper gastrointestinal tract and compare them with those in the rat and dog. METHODS: CCK receptors were localized by in vitro receptor autoradiography with 125I-[Leu15]gastrin-I and 125I-[D-Tyr-Gly, Nle(28,31)]-CCK 26-33 in stomach and gallbladder. RESULTS: High concentrations of CCK-B-gastrin receptors were detected in the midglandular region of the human fundic mucosa. CCK-A receptors were found in the basal region of the antral and fundic mucosa. CCK-A receptors were also located in the muscularis propria of antrum, fundus, and gallbladder, whereas CCK-B-gastrin receptors were only detected in gastric fundic circular muscle. Two nonpeptide CCK receptor antagonists distinguish both receptor subtypes. Comparisons among humans, dogs, and rats suggest that localization and density of CCK receptor subtypes in the upper gastrointestinal tract are species-dependent. CONCLUSIONS: Localization of CCK receptor subtypes in human upper gastrointestinal tract provides a biochemical and morphological basis for the separate regulatory roles of gastrin and CCK.
BACKGROUND & AIMS:Gastrin and cholecystokinin (CCK) are gut-brain peptides, with multiple functions in the gastrointestinal tract mediated through CCK-B-gastrin and CCK-A receptors. The receptor localization is, however, not well established in humans. The aim of this study was to investigate the distribution and pharmacological characteristics of CCK-A and CCK-B receptors in the humanupper gastrointestinal tract and compare them with those in the rat and dog. METHODS:CCK receptors were localized by in vitro receptor autoradiography with 125I-[Leu15]gastrin-I and 125I-[D-Tyr-Gly, Nle(28,31)]-CCK 26-33 in stomach and gallbladder. RESULTS: High concentrations of CCK-B-gastrin receptors were detected in the midglandular region of the human fundic mucosa. CCK-A receptors were found in the basal region of the antral and fundic mucosa. CCK-A receptors were also located in the muscularis propria of antrum, fundus, and gallbladder, whereas CCK-B-gastrin receptors were only detected in gastric fundic circular muscle. Two nonpeptide CCK receptor antagonists distinguish both receptor subtypes. Comparisons among humans, dogs, and rats suggest that localization and density of CCK receptor subtypes in the upper gastrointestinal tract are species-dependent. CONCLUSIONS: Localization of CCK receptor subtypes in humanupper gastrointestinal tract provides a biochemical and morphological basis for the separate regulatory roles of gastrin and CCK.
Authors: Eyup Akgün; Meike Körner; Fan Gao; Kaleeckal G Harikumar; Beatrice Waser; Jean Claude Reubi; Philip S Portoghese; Laurence J Miller Journal: J Med Chem Date: 2009-04-09 Impact factor: 7.446
Authors: Martin Béhé; Wolfgang Becker; Martin Gotthardt; Christa Angerstein; Thomas M Behr Journal: Eur J Nucl Med Mol Imaging Date: 2003-05-24 Impact factor: 9.236
Authors: Stephan Good; Martin A Walter; Beatrice Waser; Xuejuan Wang; Jan Müller-Brand; Martin P Béhé; Jean-Claude Reubi; Helmut R Maecke Journal: Eur J Nucl Med Mol Imaging Date: 2008-05-29 Impact factor: 9.236
Authors: Alida C Fröberg; Marion de Jong; Berthold A Nock; Wout A P Breeman; Jack L Erion; Theodosia Maina; Marion Verdijsseldonck; Wouter W de Herder; Aad van der Lugt; Peter P M Kooij; Eric P Krenning Journal: Eur J Nucl Med Mol Imaging Date: 2009-03-06 Impact factor: 9.236