Serum gastrin concentration affects the self replication rate of the enterochromaffin like cells in the rat stomach.

Tielemans, Y.; Axelson, Jan; Sundler, F.; Willems, Glenda; Håkanson, R.

doi:10.1136/gut.31.3.274

Cited by 81 publications

(32 citation statements)

References 29 publications

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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: 82%

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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Section: Mechanism Behind Mobilization Of Histamine By Ischemia-repersupporting

confidence: 82%

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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“…32,33 There is also extensive evidence that hypergastrinaemia is pivotal in the development of ECL cell-derived gastric neoplasia. In animal models of hypergastrinaemia and gastric carcinogenesis, rats, 34,35 41,42 develop either ECL cell carcinoids, adenocarcinomas in the oxyntic mucosa or both.…”

Section: Discussionmentioning

confidence: 99%

Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist netazepide (YF476) results in regression of tumours and normalisation of serum chromogranin A

Fossmark

Sørdal

Jianu

et al. 2012

Aliment Pharmacol Ther

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SUMMARY BackgroundPatients with chronic atrophic gastritis have long-term gastric hypoacidity, and secondary hypergastrinaemia. Some also develop gastric ECL cells carcinoids (type 1 GC). Most type 1 GC remain indolent, but some metastasise. Patients undergo surveillance, and some are treated with somatostatin analogues, endoscopic resection or surgery. Netazepide (YF476) is a highly selective, potent and orally active gastrin receptor antagonist, which has anti-tumour activity in various rodent models of gastric neoplasia driven by hypergastrinaemia. Netazepide has been studied in healthy volunteers.

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“…The role of gastrin in the regulation of growth (Tielemans et al 1990) of the enterochromaffin-like cell (ECL-cell) and the development of ECL-omas in the rat have been thoroughly studied. The ECL-omas are classified as carcinoids; seldomly they can metastasise (Poynter et al 1985) and can, therefore, be looked upon as slow-growing malignant tumours like other carcinoids.…”

Section: Hormones and Carcinomasmentioning

confidence: 99%

“…However, patients with antral resection and thus hypogastrinaemia, also have an increased risk of gastric carcinoma (Stalsberg & Taksdal 1971). In the oxyntic mucosa there are many neuroendocrine cell types (Sundler & Håkanson 1991) which, like the ECL-cell (Tielemans et al 1990), are probably all capable of replication. Among these cells, gastrin stimulates the growth only of the ECLcell, and on the other hand, inhibits the growth of the somatostatin producing D-cell (Chen et al 1992).…”

Section: Hormones and Carcinomasmentioning

confidence: 99%

“…The more recent description of folliclestimulating hormone receptors in the surface epithelium of the ovaries (Zheng et al 1996) makes it more probable that gonadotrophins really may play a role in carcinogenesis in the ovaries. Thus, not only steroid, but also peptide hormones could be of importance in carcinogenesis.The role of gastrin in the regulation of growth (Tielemans et al 1990) of the enterochromaffin-like cell (ECL-cell) and the development of ECL-omas in the rat have been thoroughly studied. The ECL-omas are classified as carcinoids; seldomly they can metastasise (Poynter et al 1985) and can, therefore, be looked upon as slow-growing malignant tumours like other carcinoids.…”

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confidence: 99%

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Hormones and carcinogenesis

Waldum¹

1998

Endocrine Related Cancer

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Hormones are important regulators of growth. By stimulating proliferation, hormones may increase the risk of mutation and at the same time stimulate the replication of the mutated cell. Thus, hormones are complete carcinogens. A direct carcinogenic effect of oestrogen in man is known from the occurrence of vaginal carcinomas in girls born of mothers who were treated with oestrogen during pregnancy. There are also experimental animal studies indicating that even peptide hormones may induce malignant tumours.An excellent example is the so-called enterochromaffin-like cell (ECL-cell) carcinoid of the stomach, which is caused by hypergastrinaemia and where the pathogenesis is diffuse hyperplasia, linear and nodular hyperplasia, dysplasia (with micronodules), intramucosal carcinoid, and invasive carcinoid. This sequence of events can be followed not only histopathologically but also by means of image DNA cytometry of the nuclei of the ECL-cells. As soon as clear-cut neoplasia is present, the cytometric DNA distribution pattern switches from the normal diploid type to an aneuploid one. The Endocrine-Related Cancer (1998) 5 45-48 hyperplastic lesions are all reversible, as soon as the hypergastrinaemia is eliminated. H L Waldum et al.: Hormones and carcinogenesis 46Mutations occur at cell divisions with a certain frequency. Mutagens increase the risk of mutation via a direct effect on the genes. Whether a mutation induced by a mutagen gives rise to a clinically overt tumour depends on the type of mutation and also on the replication of the mutated cell. Hormones may stimulate the growth of cells including mutated cells, and they have, therefore, been thought to be important co-carcinogens. By stimulating mitosis, hormones increase the risk of mutation solely by increasing the number of cell divisions (Ames & Gold 1990). Normally most mutations are corrected by DNA repairing mechanisms (Lindahl 1976). These repairing processes take time, and there is reason to believe that speeding up the rate of cell division may increase the risk of permanent mutations being transferred to daughter cells. Thus, hormones may not only be co-carcinogens, but in reality be among the most important carcinogens by increasing the risk of mutations in their normal target cells and at the same time stimulating the growth of the mutated cells. Hormones and growth controlThe lipid soluble steroid hormones affect the growth of their target cells by interaction with hormone responsive elements in the nucleus, affecting the regulation of gene expression (Reichel & Jacob 1993). Peptide hormones influence cellular growth by interacting with their cell membrane receptor, which, via a cascade reaction, affects gene expression. Among the peptide hormones a growth stimulatory effect has been attributed mainly to the hormones interacting with receptors coupled to the formation of inositol trisphosphate (Berridge & Irvine 1984), and only to a lesser extent to hormones coupled to adenylate cyclase (MacManus & Whitfield 1969). We (Brenna & Waldu...

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Serum gastrin concentration affects the self replication rate of the enterochromaffin like cells in the rat stomach.

Cited by 81 publications

References 29 publications

Ischemia of rat stomach mobilizes ECL cell histamine

Ischemia of rat stomach mobilizes ECL cell histamine

Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist netazepide (YF476) results in regression of tumours and normalisation of serum chromogranin A

Hormones and carcinogenesis

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