The role of protein kinase C isozymes in bombesin-stimulated gastrin release from human antral gastrin cells.
(1/23)
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. (+info)
Hypergastrinemia and enterochromaffin-like cell hyperplasia.
(2/23)
The enterochromaffin-like (ECL) cells, the most frequent endocrine cells of the oxyntic mucosa of the stomach, are under the trophic stimulus of gastrin. These cells undergo a hyperplastic increase in variety of hypergastrinemic diseases. The most widely accepted nomenclature for the description of hyperplastic proliferation has been retrospectively arranged in a sequence presumed to reflect a temporal evolution of the proliferative process. A comparative, prospective study aimed to verify, in human hypergastrinemic diseases such as atrophic body gastritis (ABG), Zollinger-Ellison syndrome (ZES) and antral gastrin cell hyperfunction (AGCH), the effect of exposure of ECL cells to different pattern of gastrin hypersecretion, is lacking. To this purpose, we studied a series of consecutive patients with ABG, ZES and AGCH at the time of first diagnosis. MATERIAL AND METHODS: The patients included in this study (124 ABG, 18 ZES and 10 AGCH) were selected on the basis of two previously performed screening studies aimed to diagnose these diseases. All patients at the time of diagnosis underwent gastroscopy, with multiple biopsies of the gastric body mucosa for the evaluation of qualitative pattern of ECL cells hyperplasia, and basal fasting gastrin determination. A sample of hypergastrinemic patients from each group was further investigated by meal-stimulation of gastrin secretion and quantitative morphometry for CgA positive gastric body endocrine cells. RESULTS: AGCH patients showed only the normal or simple hyperplasia pattern. In the ZES group, simple and linear grades accounted for 38.4 percent and 46.1 percent, respectively. MEN-I patients showed only these two patterns. The majority of ABG patients showed the presence of micronodular pattern (59.7 percent). A correlation analysis between fasting gastrin levels and grade of hyperplasia (r = 0.5580, p < 0.0001), indicates that the greater the gastrin levels, the higher is the degree of severity of ECL hyperplasia pattern. In conclusion, our data support the role of gastrin as the selective contributor to the progression of ECL cell hyperplasia in humans. (+info)
Nalpha-methyl histamine and histamine stimulate gastrin release from rabbit G-cells via histamine H2-receptors.
(3/23)
BACKGROUND: Gastrin release by Helicobacter pylori may be an important step in the pathway leading to duodenal ulceration. A histamine H3-receptor agonist was found to release gastrin from antral mucosal fragments; this was interpreted as being due to suppression of somatostatin release. H. pylori is reported to produce Nalpha-methyl histamine (NalphaMH), which is an agonist of H3 as well as other histamine receptors. H. pylori infection also recruits mast cells, which release histamine. AIM: To determine the direct effects of histamine receptor agonists on isolated gastrin cells. METHODS: Rabbit G-cells were prepared by countercurrent elutriation and cultured on 24-well plates. RESULTS: NalphaMH (10-6-10-4 M) caused a dose-dependent increase in gastrin release from a basal level of 2.3 +/- 0.2% total cell content (TCC; mean +/- S.E.M.) to a maximum of 5.1 +/- 0.7%, an increase of 117% (P < 0. 005) above basal. This was abolished by the H2-antagonist ranitidine (10-5 M), but not by immunoblockade with anti-somatostatin antibody, the H1-antagonist chlorpheniramine (10-5 M) or the H3-antagonist thioperamide (10-4 M). The histamine H2-receptor agonist dimaprit (10-6-10-4 M) increased gastrin release from 2.4 +/- 0.2% to 3.6 +/- 0.2% TCC (P < 0.001). Gastrin release was also stimulated by histamine (10-7-10-4 M) from a basal value of 3.0 +/- 0.3% to 5.4 +/- 0.5% TCC (P < 0.001). This also was inhibited by ranitidine (10-5 M) (P < 0.01). CONCLUSION: NalphaMH and histamine release gastrin from G-cells via H2-receptors; this might contribute to H. pylori-associated hypergastrinaemia. (+info)
Expression and activation of NF-kappa B in the antrum of the human stomach.
(4/23)
Both in vitro studies and experiments in mice suggest a key role for transcription factor NF-kappa B as a mediator of mucosal inflammation. Experiments in vitro show that NF-kappa B activation may be a critical event in the production of proinflammatory molecules in Helicobacter pylori-associated gastritis. This study examines the expression and activity of NF-kappa B in situ in antral biopsies of 69 consecutive patients with immunohistochemical techniques. In the uninflamed stomach, NF-kappa B was highly expressed and active in a subset of epithelial cells, which were identified as predominantly G cells. In accordance with this activity, G cells were shown to express high levels of the NF-kappa B target cytokine TNF-alpha, a well-documented stimulator of gastrin production. In patients with H. pylori-associated gastritis, NF-kappa B activity was markedly enhanced. Activation occurred preferentially in the epithelial cells. The number of cells showing activated NF-kappa B correlated with the activity of gastritis, a measure of neutrophil influx, whereas no correlation was found with the chronicity of inflammation, a measure of the presence of mononuclear inflammatory cells. This correlation is direct evidence of the importance of NF-kappa B-dependent signal transduction for neutrophil influx in H. pylori-associated gastritis. (+info)
Non-Ca2+-homeostatic functions of the extracellular Ca2+-sensing receptor (CaR) in endocrine tissues.
(5/23)
The extracellular Ca(2+)-sensing receptor (CaR) links changes in the concentration of extracellular Ca(2+) to changes in cell function. For cells involved in the control of systemic Ca(2+) concentration, this provides an efficient receptor-mediated mechanism to rapidly counteract slight fluctuations in the circulating concentration of Ca(2+). However, all cells that express the CaR are not necessarily involved in Ca(2+) homeostasis. The recent localisation of CaR expression on a variety of cell types more usually associated with non-Ca(2+)-homeostatic endocrine function may have serious repercussions for the interpretation of data in those systems which routinely culture cells under standard hypercalcaemic conditions. This short commentary considers the literature surrounding the identification of the CaR and the potential effects of its localisation on endocrine cells not directly involved in the control of systemic Ca(2+ )homeostasis. (+info)
Collagenous gastritis: a long-term follow-up with the development of endocrine cell hyperplasia, intestinal metaplasia, and epithelial changes indeterminate for dysplasia.
(6/23)
This report reviews the literature pertaining to collagenous gastritis and describes the clinicopathologic evolution of this disease in a patient during a 12-year period. We examined 109 biopsy specimens of gastric mucosa from 19 different endoscopic procedures for the severity and distribution of collagenous gastritis in a single patient. Assessments were undertaken for the presence of endocrine and gastrin cell hyperplasias and dysplastic epithelial changes. Relative to biopsy specimens from age- and sex-matched control subjects, the patient's biopsy specimens showed a significantly lower number of antral gastrin cells, along with a significant corpus endocrine cell hyperplasia, suggesting an increased risk of endocrine neoplasia. Gastric corpus biopsy specimens revealed an active, chronic gastritis, subepithelial collagen deposition, smooth muscle hyperplasia, and mild to moderate glandular atrophy. Additional findings of intestinal metaplasia and reactive epithelial changes indeterminate for dysplasia raise concerns about the potential for adenocarcinoma. (+info)
Gastrin, somatostatin, G and D cells of gastric ulcer in rats.
(7/23)
AIM: To investigate the relationship among gastrin, somatostatin, G and D cells in gastric ulcer and in its healing process in rats. METHODS: Fourty-nine Wistar rats were divided into 7 groups. The gastric ulcer model was induced by acetic acid successfully. The gastrin and the somatostatin in rat plasma, gastric fluid and antral tissue were measured by radioimmunoassay(RIA). G and D cells in antral mucosa were analyzed with polyclonal antibody of gastrin and somatostatin by immunohistochemical method and Quantimet 500 image analysis system. RESULTS: In gastric ulcer, the level of gastrin in plasma, gastric fluid, and antral tissue increased, that of somatostatin declined, and the disorder gradually recovered to the normal level in the healing process. Immunohistochemical technique of G and D cells in antral mucosa demonstrated that the number of G cells increased and that of D cells decreased, both areas of G and D cells declined, the ratio of number and area of G/D increased in gastric ulcer, and the disorder gradually recovered in the healing process. CONCLUSION: In gastric ulcer, the increased gastrin secreted by G cells, the declined somatostatin secreted by D cells, and the disordered G/D cell ratio can lead to gastrointestinal dysfunction. (+info)
G and D cells in rat antral mucosa: an immunoelectron microscopic study.
(8/23)
AIM: To investigate the gastrin secreting cells (G cells) and the somatostatin secreting cells (D cells) of antral mucosa in rats at the ultrastructural level. METHODS: Revised immunoelectron microscopic technique was used to detect the G cells and D cells in rat antral mucosa through gastrin and somatostatin antibodies labeled by colloidal gold. Also the relevant quantitative analysis regarding the granular number of colloidal gold in G cells and in D cells was conducted. RESULTS: Immunological granules of colloidal gold were distributed in G cells and D cells. Gastrin labeled golden granules or somatostatin labeled ones presented mainly as lobation-like or island-like congeries. Most of the golden congeries were observed dissociated in cytoplasms of G cells or D cells, near the basement membrane. A few golden congeries were located in nuclei. The number of golden granules in one G cell was around 107.04 +/- 19.68 and was 83.36 +/- 17.58 in one D cell. CONCLUSION: Gastrin secreting granules are located in cytoplasms and nuclei of G cells, and somatostatin secreting granules both in cytoplasms and in nuclei of D cells. The number of golden granules can be quantitatively analyzed to determine the relative amount of gastrin secreting granules or somatostatin secreting granules. (+info)