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)

Antibodies to different peptides produced from the gastrin precursor have been used in light microscopic- and electron microscopic-immunogold studies of gastrinoma tissue and normal antral mucosa. Antibodies to the C terminus of progastrin, which are known to react with the intact precursor, revealed immunoreactive material in the rough endoplasmic reticulum, Golgi region, and electron-dense granules in gastrinoma cells. In normal antrum these antibodies again revealed the Golgi region and a population of electron-dense granules. Other antibodies that react with the products of progastrin processing, but not the precursor, e.g., C-terminal and N-terminal gastrin 17 specific antibodies, revealed only granules. In addition to electron-dense granules already mentioned, the latter antibodies also revealed electron-lucent and intermediate granule populations, which in antrum were the major granule types. It is proposed that the intact precursor occurs in rough endoplasmic reticulum and Golgi; thereafter, in the immature electron-dense granules, and subsequently in electron-lucent granules, biosynthetic processing liberates gastrin 17 and gastrin 34, which are the major active products of gastrin gene expression.
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PMID:Biosynthesis of gastrin. Localization of the precursor and peptide products using electron microscopic-immunogold methods. 354 24

Solid and papillary epithelial neoplasms of the pancreas from six female patients were studied using immunohistochemistry and electron microscopy to define better their histogenesis. The tumors ranged in diameter from 5 to 15 cm (average: 9 cm), and, on cross section, most had areas of hemorrhage and necrosis, sometimes extensive. Microscopically, there was a solid and pseudopapillary pattern, with tumor cells typically having ovoid nuclei with delicate folding and indistinct nucleoli. Of note were the following: a relatively low mitotic rate (range: 0-6/20 hpf), the presence of hyaline globules (four of six cases), and collections of foam cells (three of six cases). Staining for cytoplasmic argyrophil granules was negative in each case. Ultrastructurally, the solid and papillary epithelial neoplasms of the pancreas showed evidence of acinar or ductular differentiation. Two contained zymogen granules, one had intermediate filaments (probably keratin), and three had abundant rough endoplasmic reticulum and mitochondria. Immunostaining was positive for chymotrypsin (six of six cases), trypsin (four of six), and amylase (three of six). None was positive for alpha-1-antitrypsin, neuron-specific enolase, pancreatic polypeptide, gastrin, glucagon, somatostatin, or insulin. The findings support an origin from exocrine pancreas, and follow-up indicates a low rate of malignancy, with local recurrence in two of the six patients.
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PMID:Solid and papillary epithelial neoplasm of the pancreas. An ultrastructural and immunocytochemical study of six cases. 381 76

Ultrastructural examination of the antral G cells has been carried out on 11 patients with chronic duodenal ulcer, before and after treatment with a histamine H-2 - receptor antagonist (cimetidine 1 g/day) for 8 weeks. The study demonstrated an increased area of the Golgi complex, rough endoplasmic reticulum and electron-dense granules, indicating increased G cell activity during treatment. An increased number of lysosomes was a constant feature during treatment. As an hypothesis we suggest that these lysosomes may participate in the secretory mechanism of human G cells, by destroying superfluous (Gastrin) components produced during hyperactivity.
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PMID:The antral gastrin-producing cells in duodenal ulcer patients. An ultrastructural study before and during treatment with cimetidine. 392 3

1. Analytical subcellular fractionation techniques have been applied to endoscopic human gastric antral biopsies to study the localization of gastrin, somatostatin, vasoactive intestinal peptide and the properties of the principal subcellular organelles. 2. The peptide hormones, detected by radioimmunoassay, showed particulate localizations with single peaks in the density gradients for somatostatin (modal density 1.23) and vasoactive intestinal peptide (modal density 1.17). Gastrin showed a more complex distribution with a distinct peak (modal density 1.18) and a substantial shoulder extending into the denser regions of the gradient. 3. The following organelles, characterized by their marker enzymes, were located in the density gradients: plasma membrane (5'-nucleotidase), mitochondria (malate dehydrogenase), peroxisomes (catalase), lysosomes (beta-N-acetyl-D-glucosaminidase), endoplasmic reticulum (neutral alpha-aminidase), cytosol (lactate dehydrogenase). 4. This technique can be applied to investigate disease of the gastric antrum at a subcellular level.
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PMID:Subcellular fractionation studies of human gastric antrum: localization of the mucosal peptide hormones. 611 May 6

Previous studies showed a rapid decrease of somatostatin concentration in the gut and an increase in serum gastrin levels after a single dose of the duodenal ulcerogen cysteamine. An attempt was made to identify morphologic changes that would correlate with these functional changes. Rats were killed 1, 4, 8, or 24 hr after a single dose of cysteamine and sections of gastric mucosa and pancreas were processed for electron and light microscopy. Subtle ultrastructural alterations were seen in D cells of the stomach (e.g., dilation of mitochondrial cristae and endoplasmic reticulum, and apparent increase in electron density of secretory granules) after cysteamine administration. The number of somatostatin-positive cells visualized by the immunoperoxidase technique using light microscopy was decreased in 1-4 hr but returned to normal by 24 hr. The alterations observed in the G cells after cysteamine administration are consistent with release of gastrin from mature granules and increased synthesis of the hormone. The lack of major morphologic changes in the D cells suggests that cysteamine affects somatostatin without causing cell necrosis or alteration in lysosome formation. The effect of the drug may thus be mediated at the biochemical level without marked morphologic alterations.
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PMID:The effect of the duodenal ulcerogen cysteamine on somatostatin and gastrin cells in the rat. 613 3

The ultrastructure of gastrin cells in the rat antrum was analyzed with standardized and quantitative planimetric methods. Resting and active cells were compared. The gastrin cells were activated by removal of the acid-producing part of the stomach (fundectomy). As a result of the serum gastrin concentrations were greatly elevated. Compared with gastrin cells in fasted control rats the gastrin cells in fundectomized rats were increased in number, contained fewer cytoplasmic granules, increased amount of endoplasmic reticulum, and an enlarged Golgi area. Generally, the secretory granules of the gastrin cell displayed a wide range of electron density from highly electron-dense to electron-lucent. They exhibited certain characteristic features: 1) Electron-dense granules made up a greater proportion of the total granule population in active gastrin cells than in resting cells. 2) Electron-dense granules were more frequent near the Golgi stacks than in the periphery of the cell. 3) Electron-dense granules were smaller in size than the electron-lucent granules; hence, small electron-dense granules probably represent young granules (progranules), while large, electron-lucent granules represent mature (old) granules. 4) Electron-dense granules invariably displayed a more intense immunoreactivity than electron-lucent granules. The gastrins are generated from a large precursor molecule. The post-translational processing of this precursor is reflected in the gastrin-component pattern. The gastrin-component pattern in antral extracts of fundectomized and normal fasting rats differed in that the proportion of the gastrin-4-like component was reduced, whereas the gastrin-34-like component was increased in the fundectomized rats. The results suggest a greater proportion of small gastrin components in the mature granules than in the newly formed ones, presumably due to more extensive conversion of larger forms into smaller forms with a longer granule half-life. As a result gastrin-17- and gastrin-34-like components make up a larger proportion of total gastrin in active gastrin cells than in resting gastrin cells.
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PMID:The life cycle of the gastrin granule. 703 92

1. Pylorus ligation stimulated the acid output in vagally intact rats. The serum gastrin concentration and the gastric mucosal histamine content were not affected. The gastric histidine decarboxylase activity was initially slightly elevated and then greatly reduced (12-20 hr after ligation).2. Pylorus ligation stimulated the acid output in chronically, but not in acutely, vagotomized rats. Chronic vagotomy raises the serum gastrin concentration, the gastric histamine content and histidine decarboxylase activity. The serum gastrin concentration was further raised by pylorus ligation. The histamine content was initially lowered but returned to preligation values after 20 hr. The histidine decarboxylase activity first decreased, but increased to very high levels 5-6 hr after ligation. Twelve hours after ligation it was lower than before ligation.3. Following pylorus ligation pentagastrin and histamine stimulated the acid output in vagally intact and in acutely vagotomized but not in chronically vagotomized rats. By contrast, pentagastrin raised the histidine decarboxylase activity in vagally intact and in chronically vagotomized, but not in acutely vagotomized rats.4. The two major populations of endocrine cells of the oxyntic gland area (ECL cells and A-like cells) are argyrophil, store histamine and are capable of taking up exogenous DOPA and of decarboxylating it to dopamine which is retained in the cytoplasm for several hours. As evidenced by light and fluorescence microscopy pylorus ligation did not affect their argyrophilia or their ability to produce and store dopamine.5. Pylorus ligation caused ultrastructural changes in the gastrin cells of the pyloric gland area and in the histamine-storing ECL and A-like cells of the oxyntic gland area. The two endocrine cell types in the oxyntic gland area were enlarged by pylorus ligation, more so after 16 hr than after 4 hr. The size of the gastrin cells seemed unaffected. In all three cell types pylorus ligation reduced the number of cytoplasmic granules. There was no increase in the Golgi area or in the endoplasmic reticulum in any of the endocrine cell types of the oxyntic gland area. It appears unlikely that the ultrastructural changes of the ECL and A-like cells reflect an increased rate of histamine mobilization.6. The acid response to pylorus ligation probably reflects neuronal reflex mechanisms exclusively. There is no evidence that gastrin or histamine released from gastric endocrine cells mediate the response.
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PMID:Gastric acid response to pylorus ligation in rats: is gastrin or histamine involved? 709 72

Analytical subcellular fractionation techniques using metrizamide density gradients have been used to investigate the properties of the gut hormone storage granules and the principal organelles from homogenates of normal human jejunal mucosa obtained by peroral mucosal biopsy. The individual hormones, detected by radioimmunoassay, each showed single discrete peaks in the density gradient experiments indicating localisation to single granules each with characteristic modal densities. Thus motilin showed a modal density of 1.15, gastrin 1.16, gastric inhibitory polypeptide (GIP) 1.17, enteroglucagon 1.18 and somatostatin and vasoactive intestinal peptide (VIP) 1.10 g/ml. The following organelles, characterised by their marker enzymes were located in the density gradients; plasma membrane (5'-nucleotidase) brush border (alpha-glucosidase, pH 6.0) mitochondria (particulate malate dehydrogenase), peroxisomes (catalase), lysosomes (N-acetyl-beta-glucosaminidase), endoplasmic reticulum (alpha-glucosidase, pH 8.0), cytosol (lactate dehydrogenase). These studies provide biochemical evidence of the distinct nature of the individual gut hormone storage granules and provide a basis for studying dynamic changes in the granules in response to physiological stimuli and pathological processes.
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PMID:Characterisation of gut hormone storage granules from normal human jejunum using metrizamide density gradients. 730 92

Chronic stimulation of the antral gastrin cells by elevated antral pH was achieved by fundectomy, antrum exclusion, fundectomy plus antrum exclusion, antrocolic transposition, and vagal denervation plus pyloroplasty. For comparison we studied also the effects of pyloroplasty alone and of portacaval shunting. All operations that elevated the antral pH resulted in high gastrin concentrations in serum. Particularly high concentrations were observed in fundectomized rats. Vagal denervation of fundectomized or antrum excluded rats reduced the serum gastrin concentration slightly compared with the corresponding innervated animals. Portacaval shunting reduced the gastrin concentration in serum. The antral gastrin concentration was raised or unchanged following fundectomy and vagal denervation, and reduced following antrum exclusion, antrum exclusion plus vagotomy, fundectomy plus antrum exclusion, fundectomy plus vagotomy, antrocolic transposition and portacaval shunt. The gastrin cell density in the antral mucosa was raised following fundectomy, vagotomy, and fundectomy plus vagotomy, unchanged following fundectomy plus antrum exclusion and antrocolic transposition, and reduced following antrum exclusion and portacaval shunting. Ultrastructurally the gastrin (G) cells in the excluded antrum and in the antrum of fundectomized rats showed signs of secretory activity in that the granule volume density or the number of granules per unit cytoplasm was lowered. In the fundectomized rats moreover, the endoplasmic reticulum of the G cells was increased, the Golgi area enlarged and the proportion and volume density of electron dense granules greatly increased. The granule profile diameter was not affected by either antrum exclusion or fundectomy. The results on the excluded antrum indicate that elevated antral pH per se is not sufficient to produce gastrin cell proliferation. In the fundectomized rats, where the hyperlasia of antral gastrin cells was considerable, there is the added stimulus of ingested food. In fundectomized plus antrum excluded rats this stimulus is eliminated and no proliferation ensues. The passage of intestinal material, as in the rats subjected to antrocolic transposition, did not elicit gastrin cell proliferation which seems to suggest that the character of the luminal material is important. We propose therefore that gastrin cell proliferation is due to the combined stimulation of high antral pH and passage of food. Vagal innervation is not required.
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PMID:Gastrin cell proliferation after chronic stimulation: effect of vagal denervation or gastric surgery in the rat. 735 41

The precursor for the acid-stimulating hormone gastrin provides a useful model for studies of post-translational processing because defined sites of cleavage, amidation, sulphation and phosphorylation occur within a dodecapeptide sequence. The factors determining these post-translational processing events are still poorly understood. We have used brefeldin A, which disrupts transport from rough endoplasmic reticulum to the Golgi complex, to examine the mechanisms of cleavage, phosphorylation and sulphation of rat progastrin-derived peptides. Biosynthetic products were detected after immunoprecipitation using antibodies specific for the extreme C-terminus of progastrin, followed by reversed-phase and ion-exchange h.p.l.c. Gastrin cells incorporated [3H]tyrosine, [32P]phosphate and [35S]sulphate into both progastrin and its extreme C-terminal tryptic (nona-) peptide. Ion-exchange chromatography resolved four forms of the C-terminal tryptic fragment of progastrin which differed in whether they were phosphorylated at Ser96, sulphated at Tyr103, both or neither. The specific activity of [3H]tyrosine in the peak that was both phosphorylated and sulphated was higher than in the others. Brefeldin A inhibited the appearance of [3H]tyrosine-labelled C-terminal tryptic fragment but there was an accumulation of labelled progastrin and a peptide corresponding to the C-terminal 46 residues of progastrin. Brefeldin A also inhibited incorporation of 32P and 35S into both progastrin and its C-terminal fragment. Thus phosphorylation of Ser96, sulphation of Tyr103 and cleavage at Arg94-Arg95 depend on passage of newly synthesized progastrin along the secretory pathway; as brefeldin A is thought to act proximal to the trans-Golgi, these processing steps would appear to occur distal to this point. The data also indicate that the stores of unphosphorylated C-terminal tryptic fragment are not available for phosphorylation, implying that this modification occurs proximal to the secretory granule; cleavage is known to occur in the secretory granule which suggests that it occurs after phosphorylation.
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PMID:Post-translational processing of progastrin: inhibition of cleavage, phosphorylation and sulphation by brefeldin A. 824 Feb 96


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