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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Life-long administration (greater than or equal to 2 years) of a number of long-acting gastric acid inhibitors (including H2-receptor antagonists, omeprazole and ciprofibrate) has been associated with the development of gastric enterochromaffin-like cell (ECL cell) carcinoids in rats. It has been postulated that they are a consequence of some unique property of the longer-acting acid inhibitors. There is, however, a great deal of evidence to support the hypothesis that these gastric ECL cell carcinoids develop as a result of life-long hypergastrinaemia in rats. Several lines of investigation reported here show that gastric ECL cell hyperplasia occurs when gastrin levels are increased without the use of acid-inhibiting drugs. In rats, hypergastrinaemia developed after 4 weeks' administration of exogenous gastrin (4 micrograms/kg/h). The number of gastric ECL cells per visual field had increased to 250 compared with 180 in the controls. Long-term hypergastrinaemia, induced by partial gastric corpectomy, increased plasma gastrin levels from 200 to 800 pg/ml and the density of gastric ECL cells increased from 190 to 310 cells/visual field 10 weeks after the operation. Importantly, gastric ECL cell hyperplasia, which was produced in rats by administration of omeprazole, 14 mg/kg/day for 1 year, was fully reversible following normalization of gastrin levels. Until now, gastric ECL cell carcinoids have not been reported in studies of shorter-acting, reversible H2-receptor antagonists such as ranitidine, perhaps because the correct staining techniques (i.e. Grimelius and Sevier-Munger silver stains) have not been used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gastrin and gastric enterochromaffin-like cell carcinoids in the rat. 209 10

Fifty asymptomatic patients with duodenal ulcer disease, aged 31-82 years, who had received ranitidine maintenance therapy continuously for five or more years without a symptomatic recurrence, were studied. Fasting plasma gastrin concentrations were normal (mean 24 pmol/L, S.D. +/- 22) while the post-prandial gastrin response was variable with maximum plasma concentrations ranging from 16 to 309 pmol/L. Endoscopy revealed six asymptomatic peptic ulcers. Histological examination of gastric biopsies showed mild, superficial inflammatory cell infiltration of the fundic mucosa, but more extensive inflammatory cell infiltration with some atrophy of the mucosal glands in the antral mucosa. Patchy intestinal metaplasia was evident in the antral mucosa of 18 patients. No fundic ECL cell hyperplasia was seen. Helicobacter pylori were detected in the corpus and antrum of most patients. These results suggest that maintenance treatment with ranitidine for 5 years is not associated with either significant hypergastrinaemia or with changes in the fundic mucosa which could be interpreted as pre-malignant.
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PMID:Gastric histology and plasma gastrin response to a meal in patients with duodenal ulcer disease after five years treatment with ranitidine. 210 56

Novel, powerful and long-acting inhibitors of gastric acid secretion include second generation H2-blockers and so-called proton pump inhibitors, such as omeprazole. Gastric carcinoids were found to develop in experimental animals as a consequence of continuous long-term administration of several of these highly effective anti secretory drugs. This unwanted side effect is now thought to reflect the fact (1) that pharmacological blockade of acid secretion results in hypergastrinaemia, and (2) that long-standing hypergastrinaemia gives rise to hyperplasia of certain endocrine cells, the so-called ECL cells, in the gastric mucosa. The carcinoids that develop in the rat stomach after lifelong treatment with antisecretagogues arise from the ECL cells. The proposed sequence of events is acid blockade--hypergastrinaemia--ECL cell hyperplasia--carcinoid. This concept, referred to as the gastrin hypothesis, maintains that the ECL cell hyperplasia (and possibly the carcinoids) is a consequence of long-term continuous hypergastrinaemia.
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PMID:Proposed mechanism of induction of gastric carcinoids: the gastrin hypothesis. 212

There is a significant inverse relationship between intragastric acidity and plasma gastrin concentration. All generally available gastric acid antisecretory drugs induce a release of gastrin into the circulation. The more potent the gastric antisecretory dosage regimen or drug, the greater the rise of plasma gastrin concentration. The drug-induced rise of plasma gastrin concentration is of no direct clinical concern, although it may be partly responsible for the phenomenon of tolerance to H2-blockade. Drug-induced hypergastrinemia could stimulate the proliferation of certain cell lines associated with the gastrointestinal tract, for example, the gastric epithelium, ECL cells, or colonic neoplasms.
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PMID:Drug-induced changes of plasma gastrin concentration. 218 25

Two novel monoclonal antibodies, called B11 and B13, directed exclusively against human chromogranin B (CgB) and another antibody, A11, specific for human chromogranin A (CgA), were obtained by immunization of mice with chromaffin granules, the fusion of their splenocytes, the screening of hybridomas supernatants by ELISA and immunohistochemistry, and characterization of the antibodies by two-dimensional immunoblotting. The antibodies were used in immunohistochemical tests to investigate the distribution of CgA and CgB in hormonally-identified cells of the human endocrine system. The A11 antibody confirmed the occurrence of CgA in gut EC, ECL, gastrin, secretin and neurotensin cells, pancreatic A and PP cells, parathyroid chief cells, pituitary TSH and gonadotrope cells and adrenal medullary cells. Only a fraction of CgA-immunoreactive cells in the human gut and pancreas showed C-terminus arginine-glycinamide immunoreactivity, suggesting pancreastatin storage. Both CgB antibodies showed immunoreactivity in gastrin cells, intestinal (but not gastric) EC cells, pancreatic A and PP cells, pituitary TSH and gonadotrope cells and adrenal medullary cells. In addition, the B11 antibody stained thyroid C cells and the B13 antibody stained the Golgi area of pituitary GH cells. It is concluded that most CgB is stored in the same cells showing CgA, although some CgA-rich cells, like gastric EC and ECL cells. lacked B11 and B13 immunoreactivities and some CgA-poor cells, like human thyroid C cells, showed intense B11 immunostaining.
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PMID:Immunoreactivity of hormonally-characterized human endocrine cells against three novel anti-human chromogranin B(B11 and B13) and chromogranin A (A11) monoclonal antibodies. 251 Aug 9

Based on the experience from more than 10,000 individuals omeprazole has been found to be safe and is well tolerated. Side effects are few and do not differ from those observed during H2-blocker treatment. Effects on endocrine cells observed in animals during toxicological studies include increase of antral G cells, decrease of antral D cells and increase of fundic ECL cells. The increase of G cells and the decrease of D cells is the consequence of achlorhydria achieved by very high omeprazole dosages and results in hypergastrinaemia. Hypergastrinaemia is responsible for ECL cell hyperplasia. Lifelong hypergastrinaemia in rats has been found to induce carcinoid tumours. This gastrin-carcinoid sequence is unlikely to occur in man with an omeprazole dosage recommended for treatment of peptic diseases. Therapeutic doses in man do not produce complete achlorhydria. Therefore, serum gastrin levels increase in man during omeprazole treatment only moderately and are similar in magnitude as after selective proximal vagotomy. Available results on gastric endocrine cells in patients treated with omeprazole for up to 2 years could not demonstrate significant changes in G, D and ECL cell densities. It is concluded that omeprazole is, in man, as safe as H2 blockers if administered in doses recommended for treatment of peptic diseases.
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PMID:Omeprazole: long-term safety. 269 13

Female rats were treated for 1 week with ranitidine (125-1700 mumol/kg.day, given subcutaneously by means of osmotic minipumps), the proton pump inhibitor omeprazole (10-400 mumol/kg.day orally), or vehicle. Acid secretion, plasma gastrin levels, and oxyntic mucosal histidine decarboxylase (HDC) activity were determined. Both compounds dose-dependently inhibited maximally stimulated gastric acid secretion and caused a parallel increase in plasma gastrin levels. There was very good correlation between plasma gastrin levels and HDC activity for both compounds, although higher oxyntic mucosal HDC activity was found during ranitidine treatment. The higher HDC activity in the ranitidine-treated rats indicated the presence of a histamine H2-receptor on the ECL cells. It is concluded that, regardless of what kind of antisecretory agent is used, a dose-dependent inhibition of gastric acid secretion results in a parallel increase in plasma levels of gastrin, and as a consequence the HDC activity in the rat oxyntic mucosa is increased.
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PMID:Correlation between inhibition of gastric acid secretion, plasma gastrin, and oxyntic mucosal histidine decarboxylase activity in the rat. 273 86

Gastrin-immunoreactive cells were fairly numerous in the pancreas and upper duodenum of the rat at about the time of birth. A minor population of these cells stained with antibodies directed against the N-terminal region of gastrin-34 as well as with antibodies directed against the C-terminal region. The remainder of the cells stained with the C-terminally directed antibodies only. Within a fortnight after birth all gastrin-immunoreactive cells disappeared from the pancreas and were greatly reduced in number in the duodenum; those that remained were probably CCK cells. Gastrin cells were rare in the antrum at birth and remained rare during the first days after birth. They increased in number, slowly until after weaning (15-20 days of age) and then more rapidly, until 25-30 days of age when the gastrin cell density reached that in adult rats. At the time of birth the gastrin concentration in serum was low; the subsequent increase during the first 2 weeks paralleled the development of the antral gastrin cell system. Adult postprandial serum gastrin concentrations were reached 12 days after birth. Somatostatin cells were rare in both the antral and oxyntic mucosa at birth. They increased gradually in number until about a month after birth when the cell density reached that seen in adult rats. In the oxyntic mucosa the ECL and A-like cells are the predominant endocrine (argyrophil) cell types. They were not detected until about 4 days after birth. Their number increased slowly until about 30 days of age. They did not stain argyrophil until about 2-4 weeks after birth. Parietal cells were few at birth; ultrastructurally they appeared to be in an active state and histochemically they were shown to contain carbonic anhydrase. The pH of the gastric content of newborn rats was close to 5; 15-17 days after birth the pH was about 4 in freely fed rats. In fasted rats shortly after birth the pH was about 4. Two weeks later it was around 2, which is the pH measured in older rats. Hence, the full capacity for acid secretion is probably not established until weaning. Fasting greatly lowers the serum gastrin concentration and the histidine decarboxylase activity of the ECL cells in adult rats. Before weaning, fasting produced these effects only to a minor degree.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine cells and parietal cells in the stomach of the developing rat. 286 80

The antrum-fundic section and re-anastomosis (AESR), liberates, in Wistar male rats, genuine antral peptic ulcers. They start within 20 days. They are progressive evolution, penetrating into all gastric walls. Between 7 and 8 months, they involve near organs (spleen, liver, pancreas) and produce a great inflammatory reaction of the peripancreatic ganglions. The antral peptic ulcer is induced if the gastric lesser curvature's nerves are sectioned and a concomitant pyloroplasty is done or not. The gastric hemisection, if anterior or posterior, break out the peptic ulcer only on the same side of the antrum-fundic interruption. In all this situations, except in cases of concomitant pyloroplasty, it is proved a pronounced and significantly increase of the gastric (g/kg), but not pancreatic index. In the AFSR series with nervous section on the lesser curvature and without pyloroplasty, the percentage of antral peptic ulcers in 56%. It is postulated the probably existence, at an antrum-fundic level, of a neuroendocrine center. Its nullification or disturbance by the section and re-anastomosis procedure could generate the antral ulcer and other histologic changes (increase of the "G" cells, hyperplasia of the parietal, ECL and "A like" cells) by one or various hypothetical ways: 1. Direct action, nullifying the normal blocking function of somatostative over the "G" cells and or parietal cells. 2. Disturbing or nullifying the motor pump effect of the gastric antrum, and on this way, enhancing the duodenum-gastric reflux with all know deleterious effects of the bile in the antrum particularly in an acid milieu. 3. Modifying, in the opposite direction, the sensitivity by one hand, of the "G" cells mass and by the other one, of the parietal, ECL and "A like" cells. The depression of the fundic sensitivity will induce the hyperplasia of the "G" cells, the hypersecretion of gastrin and, "a posteriori", all the secretory effects and trophic characteristic of it. 4. Disturbing the prostaglandins secretion, perhaps through a deficit of the nervous innervation, with the resulting epiphenomenon of a cytoprotection deficit mediated through the mucus and bicarbonate production. It is probably that the proposed physiopathogenic mechanism are associated and that the final result, the antral peptic ulcer is the consequence of an increase of the aggressive factors (acid, bile) and a concomitant depression of the defensive factors (cytoprotection), starting normally by the prostaglandins through the mucus and bicarbonate secretion.
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PMID:[Post-sectional antral peptic ulcer and antrofundic re-anastomosis in rats (manifestation of a probable antrofundic neuroendocrine center)]. 306 90

Clinical and experimental evidence indicates that carcinoid tumours of the stomach fundic mucosa represent another example of hormone-dependent neoplasm, gastrin being the hormone involved in tumour induction. In this context hyperplasia of fundic endocrine cells associated with chronic atrophic gastritis (CAG) and hypergastrinaemia is regarded as the most frequent preneoplastic lesion. However, the cell type involved in this hyperplasia has not been clarified. To elucidate this problem fundic endocrine cells were characterized ultrastructurally in 9 patients from which endoscopic gastric biopsies were obtained. ECL cells were the most frequent cell type in 8 cases, in 4 of which they were more numerous than all other cell types taken together. D1 cells were the most frequent type in one case while they were inconspicuous in the other cases. P cells were found with a frequency in each case intermediate between that of ECL cells and that of D1 cells. These results indicate that fundic endocrine cell hyperplasia occurring in hypergastrinaemic CAG is in most cases cytologically similar to that found in other hypergastrinemic conditions, in which the gastrin-dependent ECL cells were already found to prevail. They also explain why fundic carcinoids arising in CAG are mostly composed of ECL cells. The relation between ECL, D1 and P cells, if any, remains obscure.
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PMID:Ultrastructural characterization of fundic endocrine cell hyperplasia associated with atrophic gastritis and hypergastrinaemia. 308 27


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