Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The experience received hitherto with the treatment of omeprazole proves this drug as absolutely save and poor of side effects. ECL-cell hyperplasia and carcinoids which occur during application of very high doses of omeprazole in rats are not caused by a direct effect of omeprazole. These changes are induced by extremely elevated serum gastrin levels due to achlorhydria. However, these high doses of omeprazole are not applicated in man. Therefore, the results from animal studies can not be applied on humans. During long-term treatment with omeprazole in most patients only slight increases of serum gastrin levels and ECL-cell densities occur. Only a very few patients exhibit a progressive and marked increase of serum gastrin levels. These patients should be carefully monitored by endoscopy in regularly intervals. There is no current evidence to support the contention that omeprazole is genotoxic. Results from Burlinson on the potential of omeprazole to induce DNA damage proved to be unsounded and of no clinical relevance. Omeprazole produced negative results in all well established genotoxicity tests. The incidence of neoplasias in the stomach is not increased after long-term acid suppression as indicated by 15 years application of H2-blockers and even a longer period of experience with vagotomy. Hitherto, there is also no evidence that acid inhibition induced by omeprazole causes an increased rate of carcinoma of the stomach. The risk for promoting carcinomas of the colon by the mild hypergastrinaemia during treatment with omeprazole seems to be inferior. In addition the correlation between development of carcinomas of the colon respective rectum and hypergastrinaemia is discussed controversly.
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PMID:[Risk for developing tumors in therapy with the proton pump inhibitor omeprazole]. 837 45

We assessed the effects of pirenzepine (2 mg/kg per os) on gastric secretion and gastrin and histamine release in response to food and histamine dihydrochloride infusion in four dogs during 24 weeks of treatment and for 15 weeks after the end of treatment. The results were compared to those obtained in the same animals in control experiments, before treatment, and in four untreated dogs. Pirenzepine absorption was checked by measuring plasma concentrations. Pirenzepine led to a significant reduction in acid and pepsin secretion in response to histamine. In response to food, the reduction in secretion was concomitant with a reduction in gastrin and histamine release. Baseline concentrations of gastrin were reduced, while those of histamine were unchanged. No side effects were observed. After treatment, a long time lapse (about 15 weeks) was required for acid and pepsin secretion and gastrinemia to return to control levels, while histamine release in response to food normalized rapidly. Pirenzepine fixes selectively to M1 muscarinic receptors of the synaptic ganglion, thus inhibiting the effect of vagal stimulation, especially on pepsin secretion. Our data suggest that it might also fix to M1 receptors located on ECL cells, thereby reducing histamine release. In addition, pirenzepine probably fixes to other muscarinic receptors inhibiting gastrin release and resulting in a G and secretory cell mass reduction, probably by increasing somatostatin release.
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PMID:Effect on gastric secretion, gastrin and histamine release during and after long-term treatment by pirenzepine in dogs. 873 57

The effect of vagotomy on the development of ECL cell tumours was analyzed during drug-induced hypergastrinemia in Mastomys natalensis, a rodent prone to develop ECL cell tumours. Untreated animals were compared with animals receiving the histamine2-receptor blocker loxtidine (LOX) and with animals subjected to unilateral subdiaphragmatic vagotomy prior to loxtidine treatment (VAG+LOX). Loxtidine (2g/l) was administered in drinking water for 48 weeks to allow multiple ECL cell carcinoids to develop. Plasma gastrin levels were increased in LOX animals (94 +/- 31 pmol/l) and in VAG+LOX animals (181 +/- 59 pmol/l) compared to controls (45 +/- 4 pmol/l). Corpus weight and oxyntic mucosal thickness was almost doubled in all loxtidine-treated animals and the density of mucosal endocrine cells was increased by 65% in the LOX group and by 135% in VAG+LOX animals. No significant differences in mucosal thickness and endocrine cell density were seen when denervated and intact parts of the stomach were compared. In the VAG+LOX animals endocrine cell neoplasia was seen in 60% and dysplasia in 40% of animals compared to 40% neoplasia, 45% dysplasia and 15% hyperplasia in LOX animals. The frequency of neoplastic and dysplastic lesions did not differ between denervated and intact parts of the stomach. Untreated animals showed no neoplastic or dysplastic lesions. It is concluded that unilateral vagotomy has no protective effect on the development of ECL-cell tumours in Mastomys during hypergastrinemia, as opposed to previous studies in the rat.
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PMID:The effect of vagotomy on enterochromaffin-like cells in Mastomys natalensis. 883 19

The ECL cells in the rat stomach release pancreastatin and histamine in response to gastrin stimulation. The present study compares the release of pancreastatin and histamine from the ECL cells and the secretion of acid from the parietal cells in response to gastrin, and examines how a markedly reduced histamine content in the ECL cells will affect the gastrin-evoked release of pancreastatin and the secretion of gastrin acid. Totally isolated, vascularly perfused stomachs were prepared from fasted rats. Some of the rats had been pre-treated for 24 h with (alpha-fluoromethylhistidine (alpha-FMH), resulting in 80% depletion of oxyntic mucosal histamine (mainly ECL-cell histamine). The stomachs were perfused with rat gastrin-17, alpha-FMH, isobutyl methylxanthine (IBMX), or vehicle in various combinations for 8 h. The venous outflow was collected (30-min samples) for determination of histamine and pancreastatin-like immunoreactivity (LI) and the gastric luminal outflow was collected for determination of H+. Gastrin raised the outflow of pancreastatin-LI and histamine but did not raise the acid output unless IBMX was added. The outflow of pancreastatin-LI and histamine was greater after gastrin + IBMX (at least during the first 4-h period) than after gastrin alone. alpha-FMH reduced gastrin-evoked histamine outflow but did not affect gastrin-evoked pancreastatin-LI outflow. Also the acid output in response to gastrin + IBMX was much reduced by alpha-FMH. In conclusion, increased levels of intracellular cAMP enhanced the gastrin-evoked release of pancreastatin-LI and histamine from the ECL cells and made it possible for histamine, released from the ECL cells, to cause acid secretion from the parietal cells. ECL-cell histamine depletion reduced the gastrin-evoked acid secretion; it did not affect the gastrin-evoked release of pancreastatin-LI.
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PMID:Gastrin-evoked secretion of pancreastatin and histamine from ECL cells and of acid from parietal cells in isolated, vascularly perfused rat stomach. Effects of isobutyl methylxanthin and alpha-fluoromethylhistidine. 888 80

The ECL-cell hyperplasia and ECL-cell carcinoids occurring during long-term treatment with ciprofibrate, have been attributed to hypergastrinemia secondary to an inhibitory effect on acid secretion. However, nobody has given any explanation of the mechanism by which ciprofibrate and related phenoxyisobutyrate derivates inhibit acid secretion. Moreover, the reported inhibition of acid secretion has only been moderate, in contrast to the profound inhibition of acid secretion needed to induce similar ECL-cell changes. To re-examine the effect of ciprofibrate on gastric acidity and serum gastrin, we randomly assigned 33 male Fisher rats into three treatment groups (100 or 20 mg/kg/day of ciprofibrate and control) during a period of 4 weeks. Daily assessments of gastric acidity was done by gastric intubation, using a tube with a diameter of 2.0 mm allowing the introduction of an infant pH-catheter. Measurements were done in all animals 5 days a week. Ciprofibrate did not raise gastric pH. On the contrary, the highest dose increased the acidity. Serum gastrin levels measured in blood taken by vein puncture before the initiation of the drug treatment and on the last day of the 4 week treatment period, revealed a dose-related significant hypergastrinemic effect of ciprofibrate. The slight increase in gastric acidity in the ciprofibrate high-dose group is most likely due to the hypergastrinemia provoked by the drug. This hypergastrinemia is therefore not secondary to an inhibition of acid secretion, but may be due to a direct effect of ciprofibrate on the G-cell. The ECL-cell hyperplasia and the ECL-cell carcinoids, which develop during treatment with peroxysome-proliferators are thus due to hypergastrinemia, which is not secondary to inhibition of acid secretion.
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PMID:The peroxisome-proliferator ciprofibrate induces hypergastrinemia without raising gastric pH. 889 82

Gastrin is a well known endogenous stimulator of gastric acid. In addition, recent studies have revealed that gastrin has a growth promoting effect on gastric ECL cells. Indeed, development of ECL carcinoid tumor occurs almost exclusively in patients with hypergastrinemia such as autoimmune gastritis and Zollinger-Ellison syndrome with MEN type I. We have recently cloned human gastrin receptor gene, and by using it, we found that both gastric carcinoid tumor and endocrine cell carcinoma of the stomach express significant amount of gastrin receptor gene whereas none of gastric cancer tissue shows gastrin receptor gene expression. Thus, it is clear that gastrin plays important roles in the development of gastric carcinoid tumor as well as endocrine cell carcinoma of the stomach.
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PMID:[Gastrin and gastrin receptor]. 892 Jun 78

Histamine is a biogenic amine, which is involved in a variety of biologic processes comprising inflammation, allergic responses, neurotransmission and regulation of gastric acid secretion. The key enzyme for the generation of histamine is histidine decarboxylase (HDC), which converts the amino acid L-histidine to histamine. In this article, we review the history, biochemistry and molecular biology of this enzyme. Northern blot studies in rats demonstrated that HDC gene expression in the stomach and liver are developmentally regulated with highest levels of expression in the late fetal state, indicating a role of the gene in growth and development. In the stomach of adult rats, HDC mRNA levels are elevated after omeprazole-induced hypergastrinemia, and in situ hybridization showed that expression of HDC is restricted to the glandular area in which ECL cells are located. Since no permanent ECL cell line is at hand for in vitro studies, we established a suitable cell system by stable transfection of a human gastric adenocarcinoma cell line (AGS) with the CCK-B/gastrin receptor. Transfection of this AGS-B cell line with reporter gene constructs comprising 5'-flanking DNA sequence of the HDC gene joined to the firefly luciferase gene revealed transcriptional regulation of the HDC promoter by gastrin through a protein-kinase C-dependent pathway. Taken together, these studies are consistent with the concept of HDC transcriptional regulation as at least one phase of the overall response to gastrin.
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PMID:The regulation of histidine decarboxylase gene expression. 904 86

Acidic fibroblast growth factor (aFGF) is a member of the structurally related heparin-binding growth factor family. The best studied members of this family are aFGF and basic FGF (bFGF), which are potent mitogens and differentiation factors for mesoderm-derived cells, including fibroblasts. This study was designed to verify the immunohistochemical expression of aFGF in normal human endocrine cells of the gut and in related endocrine tumours. We examined normal gastrointestinal mucosa from seven different subjects and 41 gut endocrine tumours from different sites, including stomach, duodenum, and small and large intestine, using an aFGF polyclonal antibody with no cross-reactivity for bFGF. We localized aFGF in a fraction of serotonin-producing enterochromaffin (EC) cells of the normal gut, while it was absent in gastrin (G), CCK, secretion (S), somatostatin (D) and glicentin (L) cells. aFGF immunoreactivity was also expressed in serotonin producing EC cell tumours, but not in other functional types of gut endocrine neoplasms investigated, including gastric ECL cell, duodenal somatostatin and gastrin cell, and rectal L cell tumours. A positive correlation was found between expression of aFGF and the amount of tumour fibrous stroma, suggesting that aFGF may be involved in proliferation and activity of stromal fibroblasts.
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PMID:Immunohistochemical localization of acidic fibroblast growth factor in normal human enterochromaffin cells and related gastrointestinal tumours. 908 14

Recently, we showed that the ECL cells in the oxyntic mucosa of the rat stomach are an important source of circulating pancreastatin, a fragment of chromogranin A. The present study examined how much the ECL cells contribute to the circulating levels of pancreastatin during omeprazole-evoked hypergastrinemia. Rats received omeprazole (400 mumol kg-1 day-1) by the oral route for 3 weeks. Two weeks after the start of the treatment, the rats were subjected to a sham operation or fundectomy. The concentrations of gastrin and pancreastatin in serum were monitored before and after the operations. The ECL cells were visualized by pancreastatin immunostaining and their number was determined. The activity of oxyntic mucosal histidine decarboxylase (HDC) was measured before and after 2 weeks of omeprazole treatment. Omeprazole-induced hypergastrinemia resulted in elevated serum pancreastatin and increased oxyntic mucosal HDC activity. Pancreastatin-immunoreactive cells were equally numerous before and after 2 weeks of omeprazole treatment. After surgical removal of the ECL cells by fundectomy, the serum gastrin concentration remained high whereas the serum pancreastatin concentration decreased by 90%. We conclude that the ECL cells in omeprazole-treated rats are responsible for 90% of circulating pancreastatin.
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PMID:Evidence that rat stomach ECL cells represent the main source of circulating pancreastatin. 910 Feb 84

Porta-caval shunting enhances the trophic effects of cholecystokinin (CCK)-A receptor activation on the pancreas and of CCK-B receptor activation on the ECL cells in the oxyntic mucosa of the rat. The aim of the present study was to study the expression of CCK-A and CCK-B receptor mRNA after porta-caval shunting. Different doses of sulfated CCK-8 (CCK-8s) were administered to porta-caval shunting rats and sham-operated rats, 4 weeks after the operations. The pancreatic wet weight and DNA content were measured and the ECL cells in the oxyntic mucosa were counted after four days of continuous subcutaneous infusion. Total RNA was isolated from pancreas and oxyntic mucosa for Northern blot analysis of CCK-A and CCK-B receptor mRNA. Porta-caval shunting per se did not affect plasma CCK level nor the weight or DNA content of the pancreas, but resulted in increased number of ECL cells despite the fact that the serum gastrin concentration was reduced. The trophic response of the pancreas to low doses of CCK-8s was greater in porta-caval shunted rats than in sham-operated rats. Porta-caval shunted rats displayed an increased CCK-A receptor mRNA concentration in the pancreas (after stimulation with CCK-8s) and an increased CCK-B receptor mRNA concentration in the oxyntic mucosa. In conclusion, the porta-caval shunting-evoked enhancement of the trophic effect of CCK-A receptor activation on the pancreas and of CCK-B receptor activation on the ECL cells is associated with enhanced expression of CCK-A receptor mRNA in the pancreas and of CCK-B receptor mRNA in the oxyntic mucosa.
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PMID:Increased expression of cholecystokinin-A receptor mRNA in pancreas and cholecystokinin-B receptor mRNA in oxyntic mucosa after porta-caval shunting in rats. 910 88


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