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)

Antral gastrin secretion and gene expression is inhibited by the paracrine release of somatostatin from antral D cells. Transforming growth factor-alpha and epidermal growth factor (EGF) stimulate gastrin reporter gene constructs when transfected into pituitary GH4 cells. Somatostatin inhibits EGF stimulation of gastrin gene expression, which is in part mediated at the level of transcriptional regulation as somatostatin inhibits EGF stimulation of gastrin reporter gene constructs. Somatostatin inhibition was abolished by pertussis toxin, indicating somatostatin inhibits transcription through the inhibitory G protein Gi. Somatostatin inhibition was unaffected by vanadate and okadaic acid, implying this inhibitory pathway is mediated neither through phosphotyrosine phosphatases nor serine/threonine phosphatases, respectively. Gastrin reporter genes containing 82 base pairs of the 5'-flanking DNA were sufficient to confer both EGF responsiveness and inhibition by somatostatin in GH4 cells. However, transcription of a gastrin reporter gene construct containing only the EGF response element (GGGGCGGGGTGGGGGG), located at -68 to -53, was stimulated by EGF but was not inhibited by somatostatin. Thus, somatostatin inhibits EGF-stimulated gastrin gene transcription by a mechanism other than by interfering with cell signals elicited by the EGF receptor. Since the 82 GASCAT is inhibited by somatostatin, this result also implies that sequences adjacent to the EGF response element contain a cis-regulatory element mediating transcriptional inhibition by somatostatin. This cis-element was located using gastrin reporter genes comprising sequential segments of the human gastrin promoter sequence from the transcriptional start site to -82 in the 5'-flanking DNA. Gastrin oligonucleotide constructs lacking the D oligonucleotide (gatcCATATGGCAGGGTA), located at -82 to -69 in the 5'-flanking DNA, were not inhibited by somatostatin, indicating that a somatostatin inhibitory cis-element is located between -82 and -69 in the 5'-flanking DNA of the human gastrin promoter.
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PMID:Identification of a cis-regulatory element mediating somatostatin inhibition of epidermal growth factor-stimulated gastrin gene transcription. 135 47

The serine proteinase glandular kallikrein has been demonstrated in the gastrointestinal tract, although there is some doubt as to whether it is synthesized there or derives from exocrine-gland secretions. Using a rat pancreatic kallikrein cRNA probe we have demonstrated kallikrein-like gene expression in the corpus, duodenum, jejunum, ileum, caecum and colon, and compared the pattern of expression with that of the gastrointestinal peptides somatostatin, gastrin and glucagon. In addition, using a panel of oligonucleotide probes specific for various members of the rat kallikrein-gene family, we have shown that the kallikrein-like gene expressed appears to be expressed as true kallikrein.
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PMID:Kallikrein-gene expression in the rat gastrointestinal tract. 260 9

Cholecystokinin (CCK)-like immunoreactivity (CCK-LI) in a pool of 12 dog brains was extracted sequentially into boiling water and cold 2% trifluoroacetic acid. Gel filtration on Sephadex G-50 revealed three main molecular forms detected by a carboxyl-terminal antibody; one was eluted in the position of CCK-58 (58 amino acid residues long); a second, in the position of CCK-8; and a third, near the radioactive iodide marker. When the CCK-LI was purified by affinity chromatography using carboxyl-terminal CCK antibody followed by three steps of reversed-phase high-pressure liquid chromatography, three components were isolated and characterized by sequence microanalysis. The smallest component was the pentapeptide common to gastrin and CCK. The second peak was eluted in the same region as synthetic CCK octapeptide, and sequence analysis showed that the chemical structure of this biologically active region of canine CCK is identical to that found in sheep and pig brains. The 22-residue amino-terminal sequence of brain CCK-58 was: Ala-Val-Gln-Lys-Val-Asp-Gly-Glu-Pro-Arg-Ala-His-Leu-Gly -Ala-Leu-leu-Ala-Arg-Tyr-Ile-Gln-, the same as the sequence found for canine intestinal CCK-58 from this pool of dogs. This is the same sequence others have reported for porcine brain CCK-58 lacking nine amino acid residues (CCK-58 desnonapeptide) except that the porcine peptide had a serine in position 9. The canine CCK amino-terminal sequence differed from the sequence Ala-Gln-Lys-Val-Asn-Ser previously reported for intestinal CCK-58 purified from another pool of dog tissue, but the rest of the residues identified were identical in the two peptides. CCK-58 may be a molecular precursor of the smaller forms of CCK in brain as well as in gut.
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PMID:Isolation of a large cholecystokinin precursor from canine brain. 609 6

Individual l-amino acids were instilled intragastrically to determine possible differences in stimulation of gastric acid secretion and gastrin and pancreatic polypeptide release. Phenylalanine and tryptophan were significantly more potent stimulants of gastric acid secretion and of pancreatic polypeptide and gastrin release than any of the other amino acids tested. Smaller, but significant, responses were obtained with threonine for pancreatic polypeptide and with serine for acid secretion. We conclude that a major part of the acid-stimulating action of mixed amino acid solution can be explained by the aromatic amino acids, phenylalanine and tryptophan, which are also the most potent stimulants of gastrin and pancreatic polypeptide release. These studies suggest that the specific composition of amino acid mixtures determines the net effects of such mixtures on gastric secretion, and on release of both the antral hormone gastrin and the pancreatic hormone, pancreatic polypeptide.
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PMID:Effect of individual l-amino acids on gastric acid secretion and serum gastrin and pancreatic polypeptide release in humans. 680 40

We here ascertain whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (CD, a lysosomal hydrolase that seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori (Hp) infection. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer, and 11 with duodenitis. Tryptase and CD were measured in mucosal biopsies (body and antrum of the stomach and duodenum) using IRMA methods. Hp infection was histologically evaluated (Giemsa). Tryptase and CD levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. In Hp-positive patients the CD mucosal content was higher while tryptase mucosal levels were lower than in Hp-negative patients. Tryptase was correlated with gastrin content. CD seems to be mainly related to the phlogistic reaction of the mucosa to Hp infection; tryptase may reflect an indirect link between Hp infection, gastrin release, and the function of mast cells.
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PMID:Influence of Helicobacter pylori on tryptase and cathepsin D in peptic ulcer. 758 35

Maturation of the acid-stimulating hormone gastrin involves precursor cleavage, tyrosine sulfation, serine phosphorylation, and COOH-terminal amidation. We have used brefeldin A and incubation at 22 degrees C to determine where and when these modifications occur. Immunogold studies of gastrin cells incubated at 22 degrees C revealed swollen Golgi cisternae, the terminal regions of which were associated with an accumulation of progastrin immunoreactivity. At 22 degrees C, [3H]tyrosine and [35S]sulfate were incorporated into progastrin, but Arg94-Arg95 cleavage, and Ser96 phosphorylation, were inhibited. When pulse labeling at 22 degrees C for 120 min was followed by a chase at 37 degrees C, [35S]progastrin was cleaved at Arg94-Arg95 with a t1/2 of about 10 min, compared with about 20 min for [3H]progastrin. Approximately 60% of the COOH-terminal cleavage fragment was phosphorylated, but there was little or no incorporation of [32P]phosphate into progastrin. Addition of brefeldin A during the chase substantially inhibited cleavage of [3H]progastrin, but not [35S]progastrin. However, when pulse labeling was limited to 20 min at 22 degrees C, the presence of brefeldin A in a subsequent chase at 37 degrees C completely inhibited cleavage of [35S]progastrin. The data indicate that progastrin sulfation occurs in the trans-Golgi network, exit from which involves passage through first a brefeldin A-sensitive and then a temperature-sensitive step. Cleavage at Arg94-Arg95 and Ser phosphorylation are closely linked, occur distal to the temperature-sensitive step, and are followed by amidation in secretory granules. It is known that mature secretory granules do not phosphorylate progastrin-derived peptides, and so phosphorylation appears to coincides with, and may provide a marker for, delivery of peptide from trans-Golgi work to immature secretory granules in gastrin cells.
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PMID:Discrimination between temperature- and brefeldin A-sensitive steps in the sulfation, phosphorylation, and cleavage of progastrin and its derivatives. 805 Nov 78

Serine tRNA gene derivatives with altered anticodons were introduced to the temperature-sensitive serT42 mutant, whose tRNA(1Ser) shows a base substitution of A10 for wild type G10. When a low copy number vector-system was used, the growth and beta-galactosidase synthetic activity of the serT42 mutant were restored by complementation with the tRNA(5Ser) (T34) gene or the tRNA(1Ser) (G34) gene as well as the tRNA(1Ser) (wt) gene, but not with tRNA(5Ser) (wt), tRNA(1Ser) (A34) or tRNA(1Ser) (C34) genes at 42 degrees C. When multicopy vectors were used, the transformation even with tRNA(1Ser) (A10) gene restored the growth and beta-galactosidase synthetic activity at 42 degrees C. The tRNA(1Ser) (A10) showed no thermosensitivity in serine acceptor activity by in vitro assay. At 42 degrees C, the amount of tRNA(1Ser) (A10) in the serT42 mutant was almost the same as those in the wild type. The nucleotides in the tRNA(1Ser) (A10) were found to be fully modified like those in the wild type tRNA(1Ser). Both of the tRNAs transcribed from tRNA(5Ser) (T34) and tRNA(1Ser) (G34) genes showed serine acceptor activity. Modified nucleosides of these tRNAs were also analyzed.
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PMID:Suppression of the serT42 mutation with modified tRNA(1Ser) and tRNA(5Ser) genes. 806 26

The pathogenesis of peptic ulcer is a complex phenomenon and several factors are thought to be involved in this process. Among others, Helicobacter pylori infection, hypergastrinaemia and some proteases seem to play an essential role in inducing peptic ulceration. We investigated whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (a lysosomal hydrolase which seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori infection and mucosal content of gastrin. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer and 11 with duodenitis. Tryptase and cathepsin D were measured in mucosal biopsy specimens (body and antrum of the stomach and duodenum) using IRMA methods. Gastrin was assayed in the antral mucosa by means of a RIA method. Helicobacter pylori infection was histologically evaluated (Giemsa). Tryptase and cathepsin D levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. The mucosal content of cathepsin D, but not that of tryptase, was associated with Helicobacter pylori infection. Tryptase, on the other hand, was related to gastrin content. No correlation was found between the two enzymes. It is concluded that tryptase and cathepsin D probably reflect different pathophysiological modifications in ulcer disease. Cathepsin D seems to be mainly related to the phlogistic reaction of the mucosa to Helicobacter pylori infection; tryptase may reflect and indirect link between the action of gastrin and the function of mast cells.
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PMID:Are tryptase and cathepsin D related to Helicobacter pylori infection and mucosal gastrin in peptic ulcer? 820 35

Sp1 nuclear levels have been shown to directly correlate with the proliferative state of the cell. We therefore studied changes in the abundance of Sp1 in a rat pituitary cell line GH4 whose growth rate is regulated by epidermal growth factor (EGF). Nuclear extracts from GH4 cells treated with 10 nM EGF for at least 16 h showed a 50% decrease in Sp1 binding to a GC-rich element present in the gastrin promoter. The decrease in binding correlated with a decrease in cell proliferation, a loss of nuclear Sp1 protein and a 50-60% decrease in Sp1-mediated transactivation through an Sp1 enhancer element in transfection assays. Okadaic acid, a phosphatase inhibitor, was synergistic with the effect of EGF on Sp1 protein levels suggesting that the loss of Sp1 was mediated by phosphorylation events. This result was confirmed by showing a 2-fold increase in orthophosphate-labeled Sp1 with EGF and okadaic acid. Cycloheximide prevented the expected loss of Sp1 mediated by EGF and okadaic acid suggesting that the synthesis of a protease may mediate these events. This hypothesis was tested directly by showing that the cysteine protease inhibitor leupeptin prevented Sp1 degradation. Using the PEST-FIND computer program, the computed PEST score for human and rat Sp1 is 10.4 and 13.7, respectively, indicating that Sp1 has a domain with a high concentration of proline, glutamic acid, serine, and threonine residues as reported for a number of proteins with inducible rates of degradation. Collectively, these results indicate that sustained stimulation of GH4 cells by EGF initiates a cascade of phosphorylation events that promotes Sp1 proteolysis, decreased Sp1 nuclear levels and decreased cellular proliferation.
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PMID:Epidermal growth factor and okadaic acid stimulate Sp1 proteolysis. 919 64

The enterochromaffin-like cell (ECL) cells of the stomach are principally regulated by gastrin via a gastrin/CCK(B) receptor (G[R]) which modulates both histamine secretion and cell proliferation. In the African rodent (mastomys) hypergastrinemia generated by the histamine-2 receptor antagonist (loxtidine) results in ECL cell hyperplasia and neoplasia at 8 and 16 weeks respectively. The expression, structure and function of the G(R) during transformation is however unknown. We utilized a pure (approximately 90%) preparation of ECL cells to evaluate alterations in the G(R) utilizing immunocytochemistry, Western blot analysis, reverse transcription polymerase chain reaction (RT-PCR), 5-bromo-2-deoxyuridine uptake and phosphorylation site analysis. Although the expression of ECL cell G(R) was upregulated at both mRNA (PT-PCR) and protein (Western analysis) level, its affinity to gastrin was decreased in the hyperplastic phase and lost during transformation. The coding sequence of the G(R) of mastomys tumor ECL cells was identical to that of normal ECL cells, parietal cells and the brain. However, the mRNA sequence of the third introcytoplasmic loop of the G(R) was significantly different to other species. In addition, the G(R) exhibited phosphorylation site on serine residue(s). We have thus noted a direct correlation between hypergastrinemia and G(R) alteration and function during ECL cell transformation. It is possible that the unique mastomys gastrin receptor mediated ECL cell transformation involves the novel phosphorylation sites and a divergence in the introcytoplasmic domain.
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PMID:Gastrin receptor expression and function during rapid transformation of the enterochromaffin-like cells in an African rodent. 940 28


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