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)

Fragments of 5'-flanking and noncoding exon I sequences of the human gastrin gene were analyzed in transient expression assays after transfection of a variety of cell lines with the pSVCAT vector system. In the presence of the simian virus 40 (SV40) enhancer, the gastrin gene fragment from nucleotides -250 to +57, relative to the cap site, was as efficient a promoter as the SV40 early promoter itself. In the absence of the SV40 enhancer, gastrin gene 5'-flanking sequences had no promoter activity except in the murine neuroblastoma cell line N18TG2. In this cell line, the fragment from -1300 to +57 stimulated transcription as actively as the SV40 early promoter with its enhancer. This cell-specific gastrin gene promoter activity was in accordance with the finding that gastrin is synthesized in certain neuronal cells. Promoter activity declined with decreasing distance from the 5' end to the cap site and disappeared after removal of the gastrin gene TATA box. In vector constructions containing short vector-linker sequences homologous to a functionally important region of the SV40 enhancer, the gastrin gene fragment from -17 to +57 showed considerable promoter activity, exclusively in N18TG2. It is concluded that the truncated gastrin gene promoter plus the first exon contains a cell-specific element that may act in collaboration with upstream elements to facilitate the accumulation of transcripts.
Mol Cell Biol 1987 Dec
PMID:Cell-specific expression of the human gastrin gene: evidence for a control element located downstream of the TATA box. 283 Apr 90

Three antisera to the C-terminally extended form of gastrin or the C-terminal flanking peptide of progastrin were used in an attempt to investigate the post-translational processing of progastrin at the cellular level by light and electron microscopical immunocytochemistry. In the normal human gastric antrum, the G-cell secretory granules were found to contain both gastrin and the C-terminal progastrin determinants (progastrin 87-93, 87-95 and 93-101). Immunostaining of serial sections at the light microscopical level revealed that duodenal gastrin-containing cells also express the C-terminal progastrin determinants, as well as gastrin-34. In foetal tissue, cells containing C-terminal gastrin and the C-flanking peptide of progastrin were first seen at 8 weeks of gestation, in the duodenum. They were not found in the stomach until the 11th week. In hyperplastic G-cells and in gastrin-producing tumour cells, the level of C-terminal peptide immunoreactivity was variable and often lower than that seen in normal antrum and only minimal immunoreactivity could be detected using electron immunocytochemistry. This was interpreted as representing altered post-translational processing of progastrin in modified G-cells.
Mol Cell Probes 1987 Mar
PMID:Expression of the C-terminal flanking peptide of human progastrin in human gastroduodenal mucosa, G-cell hyperplasia and islet cell tumours producing gastrin. 284 May 76

The endocrine pancreas from four hypergastrinemic patients with recurrent peptic ulceration has been studied by light and electron microscopy. Greatly increased numbers of ducts and centroacinar cells have been observed associated with a striking increase in the number of islets and endocrine cells scattered in the acinar tissue (nesidioblastosis). The islet cells scattered throughout the exocrine parenchyma are of all the known islet cell types, with a prevalence of B and especially A cells. Many islets, probably formed de novo, are of a considerable size, have irregular contours and are in close apposition to centroacinar cells and ducts. The degree of nesidioblastosis and islet hyperplasia does not seem to be related to the plasma gastrin levels. Cytological changes have also been found in the islet cells of the hypergastrinemic patients compared with controls. These changes mainly affect the B cells and consist of a striking decrease in the number of mature secretory granules associated with a fairly extended ergastoplasm and Golgi apparatus and with a relevant increase in the number of immature granules. In two of the four patients examined, who had more severe hypergastrinemia, cytological signs of enhanced secretion are also recognized in A cells. The features indicating hypersecretion of B and A cells seem to be related to the plasma gastrin levels. The above findings indicate that chronic endogenous hypergastrinemia promotes proliferation and differentiation of islet cells and stimulates the secretory function of B cells and, to a lesser extent, of A cells, thus providing evidence for a trophic and secretagogue action of gastrin on the endocrine pancreas.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:Nesidioblastosis and islet cell changes related to endogenous hypergastrinemia. 285 99

Gastrin-releasing peptide (GRP), a bombesin-like peptide, increases plasma levels of gastrin, pancreatic polypeptide, glucagon, gastric inhibitory peptide, and insulin. GRP is produced in large quantities by small-cell lung cancer and acts as a growth factor for these cells. To determine if chromosomal changes in small-cell lung cancer are related to the expression of GRP, we chromosomally mapped the gene using human-mouse somatic cell hybrids. Twenty hybrids, characterized for human chromosomes, were analyzed by Southern filter hybridization of DNA digested with EcoRI. Human DNA cut with EcoRI yields a major band of 6.8 kb and a minor band of 11.3 kb. The 6.8 kb band segregated concordantly with chromosome 18 and the marker peptidase A. The chromosome 3 abnormalities seen in small-cell lung cancer do not correlate with the chromosomal location of GRP, suggesting that the elevated expression of this gene may be due to mechanisms other than chromosomal rearrangement.
Somat Cell Mol Genet 1987 Jan
PMID:Human gastrin-releasing peptide gene is located on chromosome 18. 302 2

We located and characterized a downstream transcriptional regulatory element in the human gastrin gene by transferring the gastrin gene 3' fragment, from which the polyadenylation signal sequence was deleted, into the shuttle vector pSCAT10 at a site located immediately downstream from the chloramphenicol acetyltransferase (CAT) gene and upstream from the simian virus 40 polyadenylation region. Study of CAT RNA derived from the hybrid plasmids, indicated regulation of transcription on the gastrin gene fragment. Analysis of deletion mutants generated from the 5' region of the fragment by CAT assay and by S1 nuclease mapping of mRNAs indicated the possible involvement of an oligothymidylate-rich sequence in transcription regulation. Mapping of gastrin gene RNA 3' ends to the 5' side proximal to the oligothymidylate-rich sequence clearly demonstrated that this sequence is a transcriptional terminator element. This unique sequence, interspersed with one or two adenines, which also functions in an orientation-dependent manner, is located 192 nucleotides downstream from the gastrin gene polyadenylation site, and serves as a transcriptional termination signal.
Mol Cell Biol 1986 Apr
PMID:A specific DNA sequence controls termination of transcription in the gastrin gene. 309 3

Gastrin biosynthesis involves a complex series of posttranslational modifications; their elucidation requires a knowledge of the structure of the gastrin precursor. The complete structure of rat preprogastrin was deduced from the nucleotide sequence of a full length cDNA clone isolated from a rat antral cDNA library. Northern blot hybridization analysis of rat antral RNA together with human antral RNA, reveals a single mRNA species of approximately 670 bases. Comparison of this sequence with those of porcine and human gastrin reveals extensive (73%) homology in the gastrin coding region as well as short regions of conserved nucleotides in the noncoding regions. The rat sequence encodes a preprogastrin of 104 amino acids which consists of a signal peptide, a 37 amino acid prosegment; and the gastrin 34 sequence, followed by a glycine (the amide donor), and flanked by pairs of arginine residues. Cleavage at an internal pair of lysine residues yields gastrin 17. Unlike the human and porcine sequences, rat preprogastrin contains a 9 amino acid carboxy-terminal extension peptide (-Ser-Ala-Glu-Glu-Glu-Asp-Gln-Tyr-Asn) which is homologous to the midportion of gastrin 17 including the site of tyrosine sulfation.
Mol Endocrinol 1987 Apr
PMID:Molecular cloning and sequencing of a rat preprogastrin complementary deoxyribonucleic acid. 345 95

The distribution and molecular forms of bombesin-like immunoreactivity (BLI) were determined in the ovine median eminence using a new, C-terminally directed antiserum. BLI was confined to neurons of the external zone of the median eminence, near small blood vessels, many of which also were immunoreactive for CRF. Each median eminence contained about 10 pmol of BLI (533 pmol/g tissue). Gel filtration and reverse-phase high pressure liquid chromatography (HPLC) demonstrated the existence of two molecular forms of BLI, which co-eluted with porcine gastrin releasing peptide (GRP)1-27 and GRP18-27 in a molar ratio of 1:2. The presence of BLI in the ovine median eminence and its co-localization in some neurons with CRF, suggest a possible role for peptides of the bombesin family in the regulation of pituitary function.
Mol Cell Endocrinol 1987 Oct
PMID:Distribution and molecular forms of immunoreactive bombesin in the ovine median eminence. 366

Somatostatin has been shown to inhibit the release of various polypeptide hormones including insulin, glucagon, gastrin, thyroid stimulating hormone, and growth hormone. The mechanism by which somatostatin inhibits the release of these various polypeptide hormones has not been fully elucidated. It has been reported that somatostatin increases the level of the second messenger cyclic GMP in rat brain and in the anterior pituitary gland. The present investigation was designed to determine if these responses seen in the anterior pituitary gland and brain were due to activation of guanylate cyclase [GTP-pyrophosphate lyase (cyclizing), E.C.4.6.1.2.], the enzyme that catalyzes the formation of cyclic GMP. Somatostatin at a concentration of 2 pM enhanced guanylate cyclase activity two-fold in rat cerebrum and anterior pituitary gland. This enhancement of guanylate cyclase activity was also seen in rat liver, pancreas, stomach, and small intestine at the same concentration of somatostatin. Increasing the concentration of somatostatin to 20 microM, caused a marked inhibition of guanylate cyclase activity in all these tissues. Dose-reponse curves done on gastric guanylate cyclase activity revealed that over a concentration range of 2 pM to 0.2 microM, somatostatin had a stimulatory effect on guanylate cyclase activity while at concentrations above 10 microM somatostatin was inhibitory to guanylate cyclase activity. The biphasic pattern of enhancement of guanylate cyclase activity at lower concentrations of somatostatin and inhibition at higher concentrations may help to explain some of the discrepancies seen with previous investigations with somatostatin, hormone release, and cyclic nucleotide metabolism.
Mol Cell Biochem 1980 Nov 20
PMID:The interrelationship of somatostatin and guanylate cyclase activity. 611 Jan 70

The effects of starvation and refeeding on intestinal cell proliferation at several sites of the rat gastrointestinal tract were studied and used as a model of altered cell proliferation in order to investigate the relationship between the rate of cell production and plasma gastrin and enteroglucagon. There was a marked fall in crypt cell production rate after four days starvation, with the proximal sites of the gut being most affected. The response to refeeding varied with site, suggesting that there was more than one mechanism for the control of intestinal cell proliferation. Plasma gastrin and enteroglucagon both fell to one fifth of their control level after starvation. Plasma gastrin increased slowly after refeeding, whilst plasma enteroglucagon increased rapidly to values significantly above control. Plasma gastrin was only correlated with crypt cell production in the duodenum, while plasma enteroglucagon was correlated with crypt cell production rate at several sites, indicating that enteroglucagon may be involved in the control of intestinal cell production.
Virchows Arch B Cell Pathol Incl Mol Pathol 1983
PMID:Cell proliferation, plasma enteroglucagon and plasma gastrin levels in starved and refed rats. 613 20

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.
Exp Mol Pathol 1983 Oct
PMID:The effect of the duodenal ulcerogen cysteamine on somatostatin and gastrin cells in the rat. 613 3


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