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At least 145 records · Page 8Linked to original sources
PubMed1996

Tumour necrosis factor alpha stimulates gastrin release from canine and human antral G cells: possible mechanism of the Helicobacter pylori-gastrin link.

There is evidence that gastric Helicobacter pylori (Hp) infection promotes duodenal ulceration by releasing gastrin. We therefore asked how Hp releases gastrin. Tumour necrosis factor alpha (TNF-alpha) is up-regulated in Hp gastritis and stimulates hormone release from pituitary cells, so we tested its effect on primary cultures of canine antral G cells and human antral fragments. TNF-alpha pretreatment (100 ng mL-1) of canine G cells significantly increased both basal (by 89%: P < 0.01) and bombesin-stimulated (by 39% P < 0.05) gastrin release. A similar pattern of increase was seen following TNF-alpha (20 ng mL-1) pretreatment of human antral fragments: basal gastrin release was increased by 38% (P < 0.05) and bombesin-stimulated by 26% (P < 0.05). This effect persisted during immunoblockade with anti-somatostatin antibody S6. We propose that TNF-alpha provides the link between Hp infection and gastrin release and thus contributes to duodenal ulceration.

Animals↗
PubMed2001

Mitogenic effect of gastrin and expression of gastrin receptors in duct-like cells of rat pancreas.

BACKGROUND & AIMS: Ductular metaplastic cells are observed during pancreas injury. Growth control by gastrin and expression of gastrin/cholecystokinin (CCK) B receptors were evaluated in these cells. METHODS: Acinoductal transdifferentiation was induced in vitro by culturing of acinar cells, and ductular metaplasia was obtained in vivo by ligation of the pancreatic ducts. Mitogenic effects of gastrin I on ductal complexes in vivo and of tetragastrin, pentagastrin, and gastrin I and II, with or without the CCK-B receptor antagonist L-365,260, on duct-like cells in vitro were analyzed by 5-bromo-2'-deoxyuridine labeling. Immunocytochemistry, Western blotting, and reverse-transcription polymerase chain reaction were applied for detection of the CCK-B receptor. RESULTS: Gastrin analogues induced a mitogenic stimulus in the duct-like cells in vitro and in ductal complexes in duct-ligated rat pancreas. Immunocytochemistry showed expression of CCK-B receptors in these models and in fetal but not normal adult exocrine pancreas. Additionally, up-regulation of CCK-B receptors during ductular metaplasia was shown by Western blotting and reverse-transcription polymerase chain reaction. CONCLUSIONS: Duct-like pancreatic epithelial cells in vitro and ductal complexes in vivo express gastrin/CCK-B receptors and proliferate in response to gastrin.

Animals↗
PubMed1982

The antral gastrin-producing cells and tissue gastrin in duodenal ulcer patients.

Morphometric estimation of the antral G-cells, radioimmunoassay estimation of the antral tissue gastrin, estimation of the antral mucosal volume and gastric acid secretion have been carried out on 10 duodenal ulcer patients. The total antral tissue gastrin varied from 52.4 to 245.1 micrograms and the mean G-cell gastrin from 0.5 to 1.8 pg. No constant relationship was found between G-cell densities and antral gastrin concentration, suggesting that no constant relationship exists between G-cell numbers and G-cell function. Furthermore, no constant relationship was observed between total antral gastrin and acid secretion.

Adult↗
PubMed1987

Characterisation of gastrin receptors on a rat pancreatic acinar cell line (AR42J). A possible model for studying gastrin mediated cell growth and proliferation.

Trophic changes of the exocrine pancreas after in vivo gastrin (G)/CCK treatment are well documented but up to now the study of the mechanisms involved is restricted by the lack of a suitable in vitro model. Nevertheless the in vivo trophic effect induced by gastrin/CCK peptides has been associated with an increase of ornithine decarboxylase (ODC) activity. In the present work, using the AR42J cell line in which CCK receptors and stimulation of amylase release by CCK peptides has already been demonstrated, we investigated the presence of gastrin binding sites and the possible modulation of proliferation by an inhibitor of ODC activity. 125I-BH-G17ns binding is saturable, reversible and specific. Potencies of the different analogues tested are G17ns greater than CCK8 greater than CCK8ns greater than or equal to G6s greater than G/CCK4. Furthermore dBt cGMP, a non-peptide antagonist for CCK receptors, does not compete for gastrin binding. This indicates the existence of a subclass of gastrin binding sites. Difluoromethyl ornithine (DFMO) (1 mM), an irreversible inhibitor of ODC, inhibits cell growth from day 3 up to day 7. This growth inhibition is dose dependent and closely related to an intracellular polyamine modulation. Putrescine and spermidine levels fell under detectable values while spermine levels increased. All these data suggest that this cell line could be a useful in vitro model to study the mechanisms of gastrin induced growth control.

Animals↗
PubMed1987

Gastrin receptor characterization: affinity cross-linking of the gastrin receptor on canine gastric parietal cells.

We applied affinity cross-linking methods to label the gastrin receptor on isolated canine gastric parietal cells in order to elucidate the nature of its chemical structure. 125I-labeled Leu15-gastrin and 125I-labeled gastrin2(-17) bound to intact parietal cells and their membranes with equal affinity, and half-maximal inhibition of binding was obtained at an incubation concentration of 3.2 X 10(-10) M unlabeled gastrin. 125I-gastrin2(-17) was cross-linked to plasma membranes or intact parietal cells by incubation in disuccinimidyl suberate. The membrane pellets were solubilized with or without dithiothreitol and applied to electrophoresis on 7.5% sodium dodecyl sulfate polyacrylamide gels. Autoradiograms revealed a band of labeling at Mr 76,000 and labeling of this band was inhibited in a dose-dependent fashion by addition of unlabeled gastrin to the incubation mixture. Dithiothreitol in concentrations as high as 100 mM did not alter the electrophoretic mobility of the labeled band. After taking into account the molecular weight of 125I-gastrin2(-17), our results suggest that the gastrin receptor on parietal cells is a single protein of Mr 74,000 without disulfide-linked subunits.

Animals↗
PubMed1978

Distribution and metabolism of gastrin. An experimental study of the fate of 123 I-gastrin in the rat as studied by external detection with a gamma camera.

In anesthetized rats, the activity distribution of intravenously administered synthetic human gastrin I, labelled with 123 I, was recorded externally by a gamma camera. In intact rats activity was found to accumulate in the kidneys and later in the stomach. After bilateral nephrectomy, the gastric apperance of activity was delayed. In both cases, the gastric activity is considered to emanate not from intact 123 I-gastrin but from free iodide, split off during gastrin degradation. The renal accumulation of gastrin in intact animals as well as the delayed gastric uptade of iodide in nephrectomized animals support the hypothesis that the kidneys are important organs for gastrin metabolism.

Animals↗
PubMed1986

Bioassay of gastrin, using the totally isolated, vascularly perfused rat stomach. A biomodel sensitive to gastrin in physiological concentrations.

A bioassay sensitive to gastrin (G 1-17) in physiological concentrations and suitable for testing of biological activity of minor amounts of radioiodinated gastrin is reported. G 1-17 was iodinated by a gentle Iodo-gen method and purified to high specific activity (1900 Ci/mmol). Totally isolated vascularly perfused rat stomachs were prepared and stimulated by graded amounts of G 1-17. Gastrin 'dose'-dependently increased the acid output from 5.7 +/- 1.0 mueq/40 min (basal) to a maximum of 58.8 +/- 10.0 mueq/40 min at a concentration of 520 pmol/l in the vascular perfusate. The lowest G 1-17 concentration that significantly increased the acid output from the basal value was 65 pmol/l, corresponding to a dose of 17.5 ng/stomach-hour. 125I-G 1-17 also increased the acid output significantly at this threshold dose. The amount of lactic acid enzymatically determined in the luminal perfusate was negligible, indicating a true parietal cell stimulation. Accordingly, a very sensitive bioassay for gastrin, suitable for testing of biological activity of G 1-17 and 125I-G, is described. Significant acid responses were obtained with physiological concentrations of gastrin, requiring less than 100 ng of hormone and labelled hormone, respectively, to show biological activity.

Animals↗
PubMedDate not supplied

The role of endogenous gastrin in the development of enterochromaffin-like cell carcinoid tumors in Mastomys natalensis: a study with the specific gastrin receptor antagonist AG-041R.

We examined the effects of a newly synthesized gastrin receptor antagonist, AG-041R, on the growth of enterochromaffin-like (ECL) carcinoid tumors in Mastomys natalensis both in vitro and in vivo. AG-041R was as potent as the well known gastrin antagonist L365,260 in inhibiting not only the gastrin-induced release of histamine from but also histidine decarboxylase (HDC) gene expression in the ECL carcinoid tumor cells. AG-041R also inhibited gastrin-induced DNA synthesis and c-fos gene expression in the tumor cells. Furthermore, AG-041R significantly inhibited the growth of the transplanted Mastomys ECL carcinoid tumors in vivo. From these data, it is concluded that endogenous gastrin is involved in the growth of ECL carcinoid tumors in Mastomys natalensis. Moreover, AG-041R is shown to have a potential as an anti-neoplastic agent for ECL carcinoid tumor of the stomach.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1976

Effect of acute hemorrhage on gastrin secretion rate and blood levels of gastrin and insulin in normal dogs and in dogs after vagotomy.

Ten dogs were used to study antral gastrin secretion in hemorrhagic shock. Dogs that had a vagotomy were compared with normal dogs. Acute hemorrhage, imposed upon operative stress, produced increased gastrin secretion in normal dogs but not in dogs after vagotomy. During the acute hemorrhage, the level of circulating gastrin in normal dogs increased to about 50 to more than 100 per cent of the control values. The concentration of gastrin in the dogs having a vagotomy was essentially unchanged in the face of acute hemorrhage. Results of this study suggest that the increased concentration of circulating gastrin in normal dogs subjected to severe stress may play a role in the development of a stress ulcer.

Animals↗
PubMed1986

[Gastrin cells and the basal level of serum gastrin in patients with insulin-dependent diabetes mellitus].

In 40 patients with insulin-dependent diabetes mellitus, the number of gastrin cells in the mucous membrane of the antrum of the stomach was measured by immunohistochemistry according to the method of L. Sternberger. The number of the cells depended on the gravity of antral gastritis, namely their number decreased as the lesion was aggravated. The basal level of serum gastrin was determined by radioimmunoassay in 144 patients with insulin-dependent diabetes mellitus. The high basal level of gastrin was recorded in patients with achlorhydria. However, no correlation was established between the gravity of antral gastritis and the basal level of serum gastrin. If the basal gastrin level is too high, the possibility of asymptomatic paresis of the stomach should be taken into account together with the other factors.

Achlorhydria↗
PubMed1979

[Effect of hypophysectomy on gastrin release and antral gastrin concentration].

Hypophysectomy resulted in a lower amount of basal serum gastrin. In hypophysectomized rats, there was a release of serum gastrin after food intake; however, the serum gastrin level was lower 30 min postprandially. The most important effect of hypophysectomy is absence of repletion of antral gastrin after an initial postcibarial depletion. We conclude that the immediate synthesis of antral gastrin after food intake is inhibited by hypophysectomy.

Animals↗
PubMed1997

Synthesis and structure-activity relationships of dual histamine H2 and gastrin receptor antagonists with noncyclic gastrin receptor antagonistic moieties.

In order to study structure-activity relationships of dual histamine H2 and gastrin receptor antagonists as well as to improve their low oral absorbability, their prototype benzodiazepine gastrin receptor antagonistic moieties were altered to a conformationally flexible noncyclic dipeptide equivalent. This skeletal modification significantly potentiated the binding affinity of hybrid compounds for the histamine H2 receptor, whereas their affinity for the gastrin receptor and receptor selectivity over the CCK-A receptor varied widely with the substituents on the gastrin moiety. Among them, [3-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl]p ropyl carbamic acid 3-[3-([(3-methoxyphenyl)[(methylphenylcarbamyl)methyl]carbamoyl]me thyl)ureido]benzyl ester (7a) showed the highest dual histamine H2 and gastrin receptor antagonistic activities. It also displayed distinct gastric acid antisecretory activity in vivo for two assays, namely, Schild's rat method by i.d. administration and the rat pylorus ligation method by oral administration. With the latter case, dose-response relationships were observed for the first time, suggesting its substantially improved oral absorbability. However, 7a did not display distinct in vivo gastric acid antisecretory activity for the assay with Heidenhain pouch dogs.

Absorption↗
PubMed1992

Immunocytochemical identification of some regulatory peptides (gastrin, gastrin-releasing peptide, neurotensin and vasoactive intestinal polypeptide) in the Harderian gland of the green frog, Rana esculenta.

The presence and distribution of gastrin-, gastrin-releasing peptide-, neurotensin- and vasoactive intestinal polypeptide-like immunoreactivity in the Harderian gland of Rana esculenta were studied at different times of the annual cycle. Gastrin-releasing peptide, neurotensin and vasoactive intestinal polypeptide-like substances were found either in the glandular cells, or in the nerve fibers surrounding the glandular acini. Gastrin-like immunoreactivity was confined to the glandular cells. The immunoreactivity varied during the annual cycle, with the greatest concentration being noted during the recovery phase of glandular secretory activity.

Animals↗
PubMed1999

The role of protein kinase C isozymes in bombesin-stimulated gastrin release from human antral gastrin cells.

Two of the most effective stimuli of gastrin release from human antral G cells are bombesin and phorbol esters. Both agonists result in activation of the protein kinase C family of isozymes, however, the exact contribution of protein kinase C to the resultant release of gastrin has been difficult to assess, possibly due to the presence of multiple protein kinase C isozymes in the G cells. The results of the present study demonstrated that the human antral G cells expressed 6 protein kinase C isozymes alpha, gamma, theta, epsilon, zeta, and mu. Of these protein kinase C, gamma and theta were translocated by stimulation of the cells by either 10 nM bombesin or 1 nM phorbol ester. Inhibition of protein kinase Cmu (localized to the Golgi complex) did not decrease bombesin-stimulated gastrin release indicating that this isozyme was not involved in the secretory process. The use of selective antagonists of the calcium-sensitive conventional protein kinase C subgroup resulted in an increase in bombesin-stimulated gastrin release and indicated that protein kinase Cgamma was involved in the desensitization of the bombesin response.

Adult↗
PubMed1989

The effect of gastrin-releasing peptide on acid secretion and the release of gastrin, somatostatin, and histamine in the totally isolated, vascularly perfused rat stomach.

We have studied the effect of gastrin-releasing peptide (GRP) on exocrine and endocrine secretion in the totally isolated, vascularly perfused rat stomach with or without concomitant infusion of a potent somatostatin antiserum. GRP (1 nM) showed a marginal acid-stimulatory effect (base line, 11.6 +/- 2.3 mumol/60 min, and after GRP, 20.0 +/- 2.2 mumol/60 min; p = 0.05). GRP significantly increased gastrin and somatostatin release to the venous effluent, and the venous gastrin concentration increased significantly during concomitant infusion of somatostatin antiserum. Furthermore, GRP inhibited histamine liberation, and somatostatin antiserum reversed this effect. The antiserum did not significantly stimulate acid secretion. Thus, the present study shows that GRP directly or indirectly affects both acid secretion and the release of gastrin, somatostatin, and histamine in the rat stomach.

Animals↗
PubMed1978

Distribution of gastrin and CCK cells in the rat gastrointestinal tract. Evidence for the occurrence of three distinct cell types storing COOH-terminal gastrin immunoreactivity.

Gastrin and cholecystokinin (CCH) cells of the rat gastrointestinal tract have been studied by immunocytochemistry and radioimmunoanalysis. With antisera directed against the COOH-terminal tetrapeptide sequence, which is common to gastrin and CCK, three distinct endocrine cell types are detected. One of the cell types predominates in the antrum, is scarce in the rest of the gut and corresponds to the gastrin cell. The second cell type is virtually confined to the duodenum and jejunum and corresponds to the CCK cell. The third cell type occurs disseminated in the small intestines, predominates in the ileum, and reacts with COOH-terminus-specific antisera only following diethylpyrocarbonate and not following formaldehyde fixation. It is possible that the third cell type stores a third member of the gastrin-CCK family of gut hormones.

Amino Acid Sequence↗
PubMed1978

ACTH-like immunoreactivity in the gastrin cell. Independent changes in gastrin and ACTH-like immunoreactivity during ontogeny.

Rat antral gastrin cells have been shown to contain ACTH-like immunoreactivity. Studies on the ontogeny of the antral gastrin cells reveal that these cells start to store gastrin before they contain detectable quantities of ACTH-like immunoreactivity. At no stage studied were duodenal gastrin cells found to contain ACTH-like peptides. The data indicate that the G cells synthetizes and/or releases the two hormonal peptides independently.

Adrenocorticotropic Hormone↗
PubMed1992

Co-transcription of the gastrin and cholecystokinin genes with selective translation of gastrin mRNA in a human gastric carcinoma cell line.

So far, no cells have been found to synthesize both of the homologous hormones, cholecystokinin and gastrin. Northern analysis and reverse transcription PCR showed, that the human gastric carcinoma cell line (AGS) expresses both a gastrin mRNA of 0.7 kb and a cholecystokinin transcript of 0.8 kb. A library of sequence-specific radioimmunoassays, cleavage with processing-like enzymes and chromatography subsequently revealed that the gastrin mRNA was translated into progastrin that was constitutively secreted into the medium (45 +/- 3 pmol/l). Neither procholecystokinin nor any of its processing products were detectable in cells and media. The results suggest that differentiation into gastrin- or cholecystokinin-producing cells may be regulated at the translational level. The gastric cell line, AGS, provides a model for studies of translational regulation of cell differentiation.

Blotting, Northern↗