Open AccessG protein-coupled cholecystokinin-B/gastrin receptors are responsible for physiological cell growth of the stomach mucosa in vivo.
Author(s) -
Aki Nagata,
Mitsuhiro Ito,
Nobuko Iwata,
Junko Kuno,
Hiroshi Takano,
Osamu Minowa,
Kazuo Chihara,
Toshimitsu Matsui,
Tetsuo Noda
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.21.11825
Subject(s) - gastrin , enterochromaffin like cell , endocrinology , cholecystokinin b receptor , medicine , receptor , cholecystokinin , cholecystokinin receptor , biology , gastric mucosa , g cell , in vivo , chromogranin a , chemistry , stomach , secretion , immunohistochemistry , microbiology and biotechnology
Many peptide hormone and neurotransmitter receptors belonging to the seven membrane-spanning G protein-coupled receptor family have been shown to transmit ligand-dependent mitogenic signals in vitro. However, the physiological roles of the mitogenic activity through G protein-coupled receptors in vivo remain to be elucidated. Here we have generated G protein-coupled cholecystokinin (CCK)-B/gastrin receptor deficient-mice by gene targeting. The homozygous mice showed a remarkable atrophy of the gastric mucosa macroscopically, even in the presence of severe hypergastrinemia. The atrophy was due to a decrease in parietal cells and chromogranin A-positive enterochromaffin-like cells expressing the H+,K(+)-ATPase and histidine decarboxylase genes, respectively. Oral administration of a proton pump inhibitor, omeprazole, which induced hypertrophy of the gastric mucosa with hypergastrinemia in wild-type littermates, did not eliminate the gastric atrophy of the homozygotes. These results clearly demonstrated that the G protein-coupled CCK-B/gastrin receptor is essential for the physiological as well as pathological proliferation of gastric mucosal cells in vivo.