Self-Replication of Enterochromaffin-Like Cells in the Mouse Stomach

Tielemans, Y.; Willems, G; Sundler, F.; Håkanson, R.

doi:10.1159/000200235

Cited by 56 publications

(34 citation statements)

References 11 publications

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“…The regulation of ECL numbers by an alteration in their cell death program may explain how hypergastrinemia increases ECL number greatly, since it is known that the renewing ECL cell population is very small in Mastomys [24]. Our observation that the ECL cell number did not return to normal 10 days after loxtidine withdrawal is consistent with the prolonged lifespan of these cells relative to other epithelial cell lineages in the stomach [26]. …”

Section: Discussionsupporting

confidence: 81%

Gastrin-Mediated Alterations in Gastric Epithelial Apoptosis and Proliferation in a <i>Mastomys</i> Rodent Model of Gastric Neoplasia

Kidd¹,

Tang

Modlin

et al. 2000

Digestion

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Background/Aims: Hypergastrinemia secondary to low acid secretion is associated with gastric carcinoid formation in Mastomys. We investigated the effect of gastrin on oxyntic epithelial apoptosis and proliferation in this model. Methods: Hypergastrinemia and mucosal hyperplasia were induced by irreversible H₂ receptor blockade with loxtidine. Gastrin levels were normalised in some animals by 10 days’ loxtidine withdrawal. Serum gastrin was determined by radioimmunoassay, proliferative, enterochromaffin-like cells and Bcl-2 protein family expression by immunohistochemisty, and apoptotic cells by terminal deoxyuridine nucleotide nick end labeling (TUNEL). Results: Proliferating cells were increased 4-fold in loxtidine-treated animals, and returned to normal upon loxtidine withdrawal. Enterochromaffin-like cell number increased 2-fold with loxtidine, and did not decrease after withdrawal. Apoptotic epithelial cells were located at the luminal surface and increased 1.8-fold with loxtidine, returning to control levels upon withdrawal. The ratio of proliferative to apoptotic cells was lower in the control and withdrawn groups than in the loxtidine group (0.26 ± 0.05 and 0.26 ± 0.08 vs. 0.77 ± 0.12). With hypergastrinemia, the expression of Bcl-2 and Bak was increased and Bax decreased in the middle of the gland. Conclusion: Hypergastrinemia is associated with alterations in both proliferation and apoptosis in Mastomys gastric mucosa. This may contribute to the pathogenesis of mucosal hyperplasia in this model.

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Section: Discussionsupporting

confidence: 81%

Gastrin-Mediated Alterations in Gastric Epithelial Apoptosis and Proliferation in a <i>Mastomys</i> Rodent Model of Gastric Neoplasia

Kidd¹,

Tang

Modlin

et al. 2000

Digestion

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“…This is unlikely because 1) omeprazole-treated rats responded to ischemia-reperfusion with histamine mobilization but not with mucosal damage and 2) clamping of the celiac artery in omeprazole-treated rats reduced the oxyntic mucosal histamine concentration and HDC activity only transiently; the histamine concentration and HDC activity were in fact back to normal 4 -9 days later. Because ECL cells have a long life span (25,26), the latter findings are in line with the view that although the cells are damaged by 30 min of ischemia, they are able to recover within a matter of days.…”

Section: Mechanism Behind Mobilization Of Histamine By Ischemia-repersupporting

confidence: 80%

Ischemia of rat stomach mobilizes ECL cell histamine

Kitano¹,

Bernsand²,

Kishimoto³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

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Microdialysis was used to study how ischemia-evoked gastric mucosal injury affects rat stomach histamine, which resides in enterochromaffin-like (ECL) cells and mast cells. A microdialysis probe was inserted into the gastric submucosa, and the celiac artery was clamped (30 min), followed by removal of the clamp. Microdialysate histamine was determined by enzyme-linked immunosorbent assay. In addition, we studied the long-term effects of ischemia on the oxyntic mucosal histidine decarboxylase activity in omeprazole-treated rats. Gastric mucosal lesions induced by the ischemia were enlarged on removal of the clamp. The microdialysate histamine concentration increased immediately on clamping (50-fold rise within 30 min) and declined promptly after the clamp was removed. In contrast, histidine decarboxylase activity of the ECL cells was lowered by the ischemia and returned to preischemic values 9 days later. Mast cell-deficient rats responded to ischemiareperfusion much like wild-type rats with respect to histamine mobilization. Pretreatment with the irreversible inhibitor of histidine decarboxylase, ␣-fluoromethylhistidine, which is known to eliminate histamine from ECL cells, prevented the rise in microdialysate histamine. Pharmacological blockade of acid secretion (cimetidine or omeprazole) prevented the lesions induced by ischemia-reperfusion insult but not the mobilization of histamine. In conclusion, ischemia of the celiac artery mobilizes large amounts of histamine from ECL cells, which occurs independently of the gross mucosal lesions. The prompt reduction of the mucosal histidine decarboxylase activity in response to ischemia probably reflects ECL cell damage. The lesions develop not because of mobilization of histamine per se but because of ischemia plus reperfusion plus gastric acid. enterochromaffin-like cell; ischemia-reperfusion; histidine decarboxylase THE GASTRIC MUCOSAL INJURY induced by ischemia-reperfusion is a useful experimental model for the study of stress ulcer formation. Clamping the celiac artery for 30 min (ischemia) followed by removal of the clamp (reperfusion) induces gross damage to the oxyntic mucosa, resulting in the formation of petechiae and sometimes ulcers deep down in the mucosa (28).

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“…Thus, the decreased mature parietal cells in CCKBR'1-mice might also affect the growth of other cell types in the gastric mucosa. Because the ECL population could be renewed through selfreplication of mature ECL cells (49), the mitogenic effect through the CCK-B/gastrin receptor could also act on these mature cells, as well as their precursor cells.…”

Section: Discussionmentioning

confidence: 99%

G protein-coupled cholecystokinin-B/gastrin receptors are responsible for physiological cell growth of the stomach mucosa in vivo.

Nagata

Ito

Iwata

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

213

160

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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.Cell proliferation and differentiation are regulated by a wide array of factors such as growth factors, cytokines, and hormones (1). Several peptide hormones such as bombesin/ gastrin-releasing peptide, angiotensin, and endothelin, and neurotransmitters such as serotonin and adrenaline have been shown to stimulate cell proliferation through their own seventransmembrane, heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors in vitro (2-5). Certain serotonin, acetylcholine, or adrenergic receptor subtypes were reported not only to stimulate cell proliferation but also to transform 3T3 fibroblasts in a ligand-dependent manner as do growth factor receptors (3-5). Very recently, G proteincoupled receptors have also been shown to involve tyrosine kinases and the Ras-mitogen-activating protein kinase pathway in their intracellular signaling as do growth factor and cytokine receptors (6-9). Although some peptides could promote the proliferation of a variety of human tumor cell lines in vivo as well as in vitro (10,11), the physiological significance of the mitogenic activity through the G protein-coupled receptor superfamily remains to be clarified.The peptide hormone, gastrin, is well characterized as a stimulant of gastric acid secretion. In addition, there is circumstantial evidence that gastrin presumably functions as a trophic factor for the gastrointestinal tissues (11, 12). Another peptide hormone, cholecystokinin (CCK), is also isolated as a stimulant of enzyme secretion by the pancreas (13). Because of the abundant expression of CCK in the central nervous system as well as in digestive organs, this hormone is also thought to act as a neurotransmitter or modulator in the brain (14). Moreover, the specific receptors for CCK and/or gastrin have been pharmacologically shown to be expressed in various human tumor cells and to stimulat...

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Self-Replication of Enterochromaffin-Like Cells in the Mouse Stomach

Cited by 56 publications

References 11 publications

Gastrin-Mediated Alterations in Gastric Epithelial Apoptosis and Proliferation in a <i>Mastomys</i> Rodent Model of Gastric Neoplasia

Gastrin-Mediated Alterations in Gastric Epithelial Apoptosis and Proliferation in a <i>Mastomys</i> Rodent Model of Gastric Neoplasia

Ischemia of rat stomach mobilizes ECL cell histamine

G protein-coupled cholecystokinin-B/gastrin receptors are responsible for physiological cell growth of the stomach mucosa in vivo.

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