Gastrin receptor genes are expressed in gastric parietal and enterochromaffin-like cells ofMastomys natalensis

Asahara, Masahiro; Kinoshita, Yoshikazu; Nakata, Hirohisa; Matsushima, Yumi; Naribayashi, Yoko; Nakamura, Akira; Matsui, Toshimitsu; Chihara, Kazuo; Yamamoto, Jun; Ichikawa, Atsushi; Chiba, Tsutomu

doi:10.1007/bf02090363

Cited by 56 publications

(39 citation statements)

References 41 publications

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“…The epithelial cells expressing GR mRNA include not only ECL cells but also parietal and chief cells, confirming earlier descriptions [1,21,37].…”

Section: Discussionsupporting

confidence: 88%

“…In the brain, it has been reported that cholecystokinin-B (CCK-B) receptors are identical to gastrin receptors (GRs) [1,17]. CCK-B receptors predominate in the CNS [7,15], but CCK-B receptors have also been identified in smooth muscle cells of the gastrointestinal tract [20], the function of which may be regulation of motility of bowel and gallbladder [16], and CCK-B has also been shown to regulate proliferation firstly of AR42-J pancreatic carcinoma cell line in rats, and subsequently of cells of gastrointestinal tract [18].…”

mentioning

confidence: 99%

“…To elucidate the mechanism of development of ECL cells and carcinoid tumors, it is important to understand the distribution of cells expressing GR mRNA [1] . In this study, we investigated the development of ECL cell hyperplasia, induced by surgical treatment [22] without administration of any chemical mediator, and studied the distribution of cells expressing GR mRNA in the oxyntic mucosa of hypergastrinemic rats.…”

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confidence: 99%

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Detection of Cholecystokinin B/Gastrin Receptor mRNA Expressing Cells in the Stomach of Hypergastrinemic Rats.

Kawasaki

Fujimura

Mori

et al. 1995

Acta Histochem. Cytochem

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“…The epithelial cells expressing GR mRNA include not only ECL cells but also parietal and chief cells, confirming earlier descriptions [1,21,37].…”

Section: Discussionsupporting

confidence: 88%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Detection of Cholecystokinin B/Gastrin Receptor mRNA Expressing Cells in the Stomach of Hypergastrinemic Rats.

Kawasaki

Fujimura

Mori

et al. 1995

Acta Histochem. Cytochem

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“…CCKA-Rs exhibit a 500-to 1,000-fold higher affinity for sulfated analogs of CCK than for gastrin, whereas CCKB-Rs have approximately equal affinity for both sulfated and non-sulfated peptide analogs of CCK and gastrin (32,34,46,47). CCKB-Rs are present in parietal, ECL, and probably somatostatin cells (2,4,23,27,28,41 (2,28). Immunohistochemical studies have also demonstrated the distribution of CCKB-R in the same cell types (41).…”

mentioning

confidence: 99%

Gastrin stimulates the growth of gastric pit cell precursors by inducing its own receptors

Nakajima

Konda

Izumi

et al. 2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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.-Gastrin/CCK-B receptors (CCKB-Rs) are present on parietal and enterochromaffin-like cells in the gastric mucosa but not on pit cells in the proliferative zone. Because serum gastrin levels are well correlated with the growth of the gastric pit, we examined whether pit precursor cells express CCKB-Rs using hypergastrinemic transgenic mice and a mouse pit precursor cell line, GSM06. In situ hybridization indicated that CCKB-R mRNA was limited to the lower one-third of the mucosa in control mice, whereas it was faintly distributed along the midto low glandular region in the hypergastrinemic transgenic mouse mucosa. CCKB-R-positive midglandular cells appear to have a pit cell lineage; therefore, GSM06 cells were used for an [ 125 I]gastrin binding study. [ 125 I]gastrin bound to the membrane fraction of the GSM06 cells when precultured with gastrin. Gastrin dose dependently induced CCKB-R expression in GSM06 cells and stimulated their growth. Thus these findings suggest that gastrin directly stimulates the growth of the pit cell lineage by inducing its own receptor in pit cell precursors. gastric mucosal growth; gastric surface mucous cell; gastrin/ cholecystokinin-B receptor GASTRIN CONTROLS THE GROWTH of gastric mucosa (14,15). Hypertrophied gastric mucosa is observed in patients with gastrin-producing tumors and also in rats infused continuously with gastrin (5, 31). In contrast, hypotrophic or atrophic mucosa results from fasting in rats whose serum gastrin levels become low (35). The glandular cell components, which include parietal, chief, and enterochromaffin-like (ECL) cells, have relatively long lifespans of 3, 5, and 2 mo, respectively (17). Thus the atrophic change induced by fasting in rats appears to be due mainly to a shortage of pit/gastric surface mucous cells that survive only 3 days in rodents (18). It is not known, however, whether the pit cells and their precursors express gastrin receptors.The physiological roles of gastrin in mucosal growth were recently studied using hypergastrinemic animal models. Wang et al. (45) produced transgenic (TG) mice expressing gastrin under the control of an insulin promoter, which resulted in gastrin production in pancreatic ␤-cells. They reported that gastrin enhances gastric mucosal growth, whereas progastrin preferentially stimulates colonic mucosal growth. They further demonstrated that hypergastrinemic TG mice develop gastric atrophy and eventually gastric cancer (44) and postulated that the hyperplasia of the foveolar pit cell region and the decrease in the parietal cell mass are due, at least in part, to gastrin-stimulated upregulation of growth factors, including heparin binding-epidermal growth factor-like growth factor (HB-EGF) and transforming growth factor-␣ (TGF-␣). Moreover, infection with Helicobacter felis accelerates the formation of gastric cancer in a synergistic manner with hypergastrinemia in hypergastrinemic TG mice (44).We generated TG mice with hypergastrinemia by expressing a human gastrin transgene (19). The gastric mucosa of these mice...

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“…One possible explanation for the more frequent neuroendocrine tumors over gastric adenocarcinoma in patients with hypergastrinemia may be related to the finding that although the CCK-B receptor is present on parietal cells, it is expressed more abundantly in ECL cells of the stomach. 85,86 In addition to responding to the proliferative effects of gastrin, studies also have shown that the parietal cells respond to other trophic factors secreted by the ECL-like cells by a paracrine mechanism including secretion of Reg protein, 87 heparin-binding EGF, 88 and even histamine. 89 With more sophisticated technology using lineage tracing, researchers have confirmed the presence of CCK-B receptors on the antrum stem cells that do not respond to gastrin-17.…”

Section: -63mentioning

confidence: 99%

Gastrin and gastric cancer

&NA;

1993

European Journal of Gastroenterology & Hepatology

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SUMMARYThe gastrointestinal peptide, gastrin, stimulates growth of gastric adenocarcinoma (gastric cancer) through the cholecystokinin-B receptors that are overexpressed in this malignancy. Serum gastrin levels may be increased secondary to chronic administration of proton pump inhibitors, atrophic gastritis, Helicobacter pylori infection, or from de novo gastrin expression from the gastric cancer epithelial cells. Strategies to interrupt the interaction of gastrin at the cholecystokinin-B receptor may provide a novel approach to the treatment of gastric cancer.Gastric cancer is the third leading cause of cancer-related mortality worldwide. Despite progress in understanding its development, challenges with treatment remain. Gastrin, a peptide hormone, is trophic for normal gastrointestinal epithelium. Gastrin also has been shown to play an important role in the stimulation of growth of several gastrointestinal cancers including gastric cancer. We sought to review the role of gastrin and its pathway in gastric cancer and its potential as a therapeutic target in the management of gastric cancer. In the normal adult stomach, gastrin is synthesized in the G cells of the antrum; however, gastrin expression also is found in many gastric adenocarcinomas of the stomach corpus. Gastrin's actions are mediated through the G-protein-coupled receptor cholecystokinin-B (CCK-B) on parietal and enterochromaffin cells of the gastric body. Gastrin blood levels are increased in subjects with type A atrophic gastritis and in those taking high doses of daily proton pump inhibitors for acid reflux disease. In experimental models, proton pump inhibitor-induced hypergastrinemia and infection with Helicobacter pylori increase the risk of gastric cancer. Understanding the gastrin:CCK-B signaling pathway has led to therapeutic strategies to treat gastric cancer by either targeting the CCK-B receptor with small-molecule antagonists or targeting the peptide with immune-based therapies. In this review, we discuss the role of gastrin in gastric adenocarcinoma, and strategies to block its effects to treat those with unresectable gastric cancer. (Cell Mol Gastroenterol Hepatol 2017;4:75-83; http://dx

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Gastrin receptor genes are expressed in gastric parietal and enterochromaffin-like cells ofMastomys natalensis

Cited by 56 publications

References 41 publications

Detection of Cholecystokinin B/Gastrin Receptor mRNA Expressing Cells in the Stomach of Hypergastrinemic Rats.

Detection of Cholecystokinin B/Gastrin Receptor mRNA Expressing Cells in the Stomach of Hypergastrinemic Rats.

Gastrin stimulates the growth of gastric pit cell precursors by inducing its own receptors

Gastrin and gastric cancer

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