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)

With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable electron density. According to most authors, they represent a distinct cell type and not just a variant of the G-cells. It may be very difficult, however, to separate certain forms of D1-cells from functionally altered G-cells. 5. The A-cell can be found in the gastric mucosa of certain animal species, where it has been demonstrated by immunocytochemistry with antisera to gut-glucagon. This cell type does not occur in the human gastric mucosa. 6...
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PMID:[Pathomorphologic studies of the endocrine cells in the gastrointestinal mucosa. Physiology, cytochemistry and ultrastructure (author's transl]. 19 Aug 18

Up to seven endocrine cell types have been identified ultrastructurally in the pancreas, including glucagon A cells, insulin B cells, somatostatin D cells, pancreatic peptide F cells and 5-hydroxytryptamine EC cells. In addition, D1 cells, which have been proposed as the cell type producing VIP and possible P cells of unknown function are seen. Various patterns of endocrine cell differentiation have been found in 20 endocrine pancreatic tumours. Well and poorly differentiated B cells have been identified in 6 insulinomas, diagnostic G cells in 3 out of 7 gastrinomas, D1 and/or F cells in 7 diarrheogenic tumours. Moreover, cells apparently unrelated to the prevalent clinical syndrome have been noted in 8 of the 20 tumours. Granular non diagnostic cells (poorly diagnostic gastrin cells? D1 cells?) were particularly frequent in gastrinomas; agranular or poorly granular cells, either by "active" or "Stem cell" type, were present in nearly all tumours, particularly in diarrheogenic tumours, gastrinomas and malignant insulinomas. A cytological classification of pancreatic endocrine tumours is proposed.
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PMID:The endocrine cells of the pancreas and related tumours. Ultrastructural study and classification. 19 45

Intravenous infusion of isoproterenol, a beta-adrenergic receptor stimulatory agent, increased serum gastrin concentration significantly more in patients with a duodenal ulcer than in healthy subjects. The rise in pulse rate, blood glucose concentration and in serum insulin was the same in both groups of subjects. Gastrin secretion was also increased significantly more in the patients than in the control subjects after a beef-meal. Basal serum gastrin concentrations were higher in the patients than in the control subjects and correlated to the rise in serum gastrin during both tests in the patients with a duodenal ulcer. Isoproterenol and meal stimulated gastrin secretion, expressed as percent of the basal value, were twice as higher in the patients as in the control subjects. The combined administration of isoproterenol and the meal had an additive effect on the rise in serum gastrin. Isoproterenol stimulated gastrin secretion was completely suppressed by propranolol, a beta-adrenergic receptor blocking agent, which had no effect on meal stimulated gastrin secretion. It is concluded that the mechanism of the hypersecretion of gastrin in patients with a duodenal ulcer did not involve a specific abnormality of the beta-adrenergic receptor or the receptor which recognized proteins and their digested products. There is no established role of beta-adrenergic receptor activity in the hypersecretion of gastrin in patients with duodenal ulcers. It is suggested that the beta-adrenergic receptor may have some yet unknown function unrelated to the acute secretory response of gastrin.
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PMID:The role of the beta-adrnergic receptor in the secretion of gastrin: studies in normal subjects and in patients with duodenal ulcers. 97 1

Treatment of chickens, hamsters and guinea-pigs with large doses of the long-acting antisecretory agent omeprazole for 10 weeks resulted in elevated serum gastrin levels and in increased stomach weight and mass of oxyntic mucosa. Also the antral gastrin cell density was increased. Another striking effect was the hyperplasia of the histamine-producing enterochromaffin-like (ECL) cells - a prominent endocrine cell population with unknown function-in the oxyntic mucosa. Accordingly, the gastric mucosal histamine concentration and rate of histamine formation were increased in all three species. The results suggest that marked and long-lasting suppression of acid secretion leads to elevated serum gastrin levels and diffuse ECL cell hyperplasia not only in the rat, as previously seen, but also in the chicken, hamster and guinea-pig; this hyperplasia is associated with accelerated histamine formation in all three species. The following sequence of events is suggested to occur in mammalian as well as submammalian vertebrates: suppression of acid secretion - hypergastrinaemia - ECL cell hyperplasia.
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PMID:Hypergastrinaemia induced by acid blockade evokes enterochromaffin-like (ECL) cell hyperplasia in chicken, hamster and guinea-pig stomach. 323 48

The stomach is rich in endocrine cells, most of which are still unidentified with respect to the peptide hormones they produce. The endocrine cell populations in the antrum usually differ from those in the oxyntic mucosa. Gastrin cells are found in the antrum and respond readily to stimuli from the gastric lumen, such as changes in the pH and the presence of food. In order to study the functional control of the antral gastrin cell, rats were subjected to different kinds of surgery. The serum gastrin concentrations in the various experimental groups were measured 8-10 weeks after the operations. Elevated antral pH raised the serum gastrin concentration. The combination of elevated antral pH and the passage of food over the pyloric glands produced gastrin cell hyperplasia. The operation that was most effective in inducing gastrin cell hyperplasia was removal of the acid-producing part of the stomach. Interestingly, gastrin cell hyperplasia was seen also after bilateral truncal vagotomy, indicating that an intact vagal innervation is not essential for the development of gastrin cell hyperplasia. Enterochromaffin-like (ECL) cells are endocrine/paracrine cells that are numerous in the acid-producing part of the stomach in many species. In the rat, they occur predominantly in the basal half of the oxyntic mucosa and produce and store histamine. The ECL cells have an unknown function and do not seem to respond to stimuli from the gastric lumen. They are activated by circulating gastrin and by vagal excitation. Gastrin mobilises histamine from these cells and activates the histamine-forming enzyme, histidine decarboxylase. Long-term hypergastrinaemia produces diffuse ECL cell hyperplasia, whereas hypogastrinaemia (following removal of the endogenous stores of gastrin by antrectomy) reduces the ECL cell number. Portacaval shunt brings about a marked increase in the number of ECL cells through an unknown mechanism. Also neuronal stimuli are important for the trophic control of the ECL cells. Studies of unilaterally vagotomised rats showed reduced weight and thickness of the oxyntic mucosa as well as a markedly reduced number of ECL cells on the denervated side. Gastric carcinoids in man are rare tumours predominantly made up of ECL cells. The incidence of such tumours is increased in patients with hypergastrinaemia (pernicious anaemia, Zollinger-Ellison syndrome). A diffuse ECL cell hyperplasia is a common finding in such patients, which is in keeping with the known gastrin sensitivity of the normal ECL cell in the rat.
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PMID:Activation and hyperplasia of gastrin and enterochromaffin-like cells in the stomach. 353 78

The rat pancreatic carcinoma cell line AR4-2J was screened for growth-associated genes linked to the mitogenic effect of the novel gut brain hormone, pituitary adenylate cyclase activating polypeptide (PACAP). Using the mRNA differential display technique, we identified and sequenced an unknown rat gene, PACAP-responsive gene 1 (PRG1), which is highly homologous to gly96, a novel murine gene of unknown function. The PRG1 cDNA sequence of 1.1 kb encodes a 160-amino acid protein. Using targeted PCR, the gene structure of PRG1, constituting 0.6 kb of the promotor region, and the DNA coding region, including a single 107-bp intron, were established from rat genomic DNA. In AR4-2J cells, PACAP(1-38) increased PRG1 mRNA levels up to 10-fold in a rapid (30 min), transient (3-6 h), and dose-dependent (ED50, <1 nM) fashion. The growth-stimulating gastrointestinal hormones cholecystokinin and gastrin showed a similar degree of PRG1 induction, and the PACAP-related peptides vasoactive intestinal peptide and secretin were without effect. The transcriptional inhibitor actinomycin D, various protein kinase C inhibitors, and the calmodulin inhibitor W-7 strongly reduced PRG1 induction by PACAP, whereas the translational inhibitor cycloheximide potently increased PRG1 mRNA levels in unstimulated and PACAP-stimulated cells. Feedback-mediated hyperplasia of the rat exocrine pancreas induced by oral treatment of rats with the protease inhibitor camostate (FOY-305) was preceded by a 15-fold transient elevation of PRG1 mRNA levels. These data suggest that PRG1 is an early-response gene linked to PACAP-induced growth of AR4-2J cells as well as to hyperplasia of the rat exocrine pancreas in vivo.
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PMID:PRG1: a novel early-response gene transcriptionally induced by pituitary adenylate cyclase activating polypeptide in a pancreatic carcinoma cell line. 865 10

beta-Microseminoprotein is a 10-kDa disulphide-rich protein with unknown function which is present in the mucus of the airways, gastrointestinal tract and urogenital tract. In this paper, an investigation of the distribution of beta-microseminoprotein in the human stomach is reported. Immunohistochemistry and in situ hybridization were used. beta-Microseminoprotein was found to be localized mainly in the antrum part of the stomach and in two types of cells. Cells of the most abundant type (designated M-cells) were the neutral mucin-containing cells in the bottom part of the gastric glands and the surface epithelium. Virtually all these cells contained both beta-microseminoprotein mRNA and protein product. Cells of the second type (designated E-cells) were found in a zone one-third up from the bottom of the gastric glands, where gastric endocrine cells are located. The E-cells were fewer than the M-cells and usually solitary. They seemed to have a high concentration of protein compared with their low mRNA level. The majority of the E-cells contained chromogranin A and gastrin. The observations made have implications for the understanding of the differentiation of the mucosal cells in the antrum of the stomach and form a basis for future studies of beta-microseminoprotein in gastric disease.
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PMID:Immunohistochemical and in situ hybridization studies of beta-microseminoprotein in the human gastric mucosa. 946 51

The homeobox gene product Nkx 6.1 is of unknown function but is expressed in the pancreas and the antropyloric mucosa of the stomach. In the adult pancreas, Nkx 6.1 possesses an insulin cell-restricted distribution, whereas its localization in the stomach is unknown. We now show that the vast majority of serotonin-producing enterochromaffin cells of the antropyloric mucosa contain Nkx 6. 1-immunoreactive nuclei. In addition, a subpopulation of cells co-storing serotonin and gastrin display Nkx 6.1-positive nuclei. Such cells have been postulated to represent precursors of mature gastrin and serotonin cells. The nuclei of the co-storing cells have previously also been found to be positive for another homeodomain protein, Pdx-1. Pdx-1-deficient animals were therefore investigated and were found to be devoid of Nkx 6.1-positive nuclei. Our data show that Pdx-1 is needed for Nkx 6.1 expression and suggest a role for Nkx 6.1 in the maturation of gastrin- and serotonin-positive precursor cells.
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PMID:Homeobox gene product Nkx 6.1 immunoreactivity in nuclei of endocrine cells of rat and mouse stomach. 960 82

This review discusses the current concepts for the classification of gastric endocrine cells subdivided according to the type of mucosa in which they are located. In the oxyntic mucosa, the most important cell type is the ECL cell, involved in the synthesis and secretion of histamine. Proteins involved in many aspects of the biology of ECL cells including the response to the gastrin stimulus, membrane transport and docking, prevention of apoptosis, calcium homeostasis, autocrine activity, and maintenance of the differentiated cell phenotype have been localized to this cell type. Other cells of the oxyntic mucosa include: the D and EC cells producing somatostatin and serotonin, respectively, delivered through long cell processes; the X (or A-like) cells, possibly producing endothelin; and the D(1) and P cells of unknown function and possibly representing morphological variants of other cell types. In the antral mucosa, the three important cell types are represented by: the gastrin-producing G cells; the somatostatin-producing D cells, which are anatomically and functionally associated with G cells; and the serotonin-producing EC cells, which are located at the bottom of antral glands.
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PMID:Classification of gastric endocrine cells at the light and electron microscopical levels. 1070 43

This report describes the molecular cloning and pharmacological characterization of a transiently expressed chicken brain cholecystokinin receptor (CCK-CHR) in COS-7 cells. A polymerase chain reaction (PCR)-based cloning strategy was applied using: (1) an initial PCR with deoxyinosine-containing primers designed to target conserved regions in CCK receptors, followed by (2) rapid amplification of cDNA ends (RACE), and (3) full-length PCR of the CCK-CHR cDNA. The full-length cloned bicistronic CCK-CHR cDNA contained a short upstream open reading frame (uORF) coding for a putative six-amino-acid-long peptide of unknown function, followed by a long open reading frame (lORF) encoding the 436-amino-acid-long CCK-CHR receptor protein. At the amino acid level, the CCK-CHR shared approximately 50% homology with mammalian and Xenopus laevis CCK receptors. The pharmacological profile of CCK-CHR resembled that of CCK-B receptors using agonists (CCK-8, CCK-4, gastrin-17), whereas CCK-CHR showed higher affinity for the CCK-A receptor antagonist, devazepide, than for the CCK-B receptor antagonist, L-365,260. To the best of our knowledge, this is the first description and functional expression study of a cloned chicken CCK receptor cDNA.
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PMID:Molecular cloning of an unusual bicistronic cholecystokinin receptor mRNA expressed in chicken brain: a structural and functional expression study. 1276 38


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