Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gastrointestinal peptide response to food was assessed in 6 healthy subjects following oral administration of 40 mg omeprazole. There was a small but statistically significant increase in basal plasma gastrin six hours after the dose of omeprazole, but the post-prandial plasma gastrin was not significantly increased. There was no significant effect on basal or post-prandial levels of somatostatin, insulin, pancreatic glucagon, enteroglucagon, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, neurotensin, cholecystokinin, secretin, vasoactive intestinal peptide and gastrin-releasing peptide or blood glucose concentration.
 ...
PMID:Effect of single dose of omeprazole on the gastrointestinal peptide response to food. 636 14

The gastrointestinal peptide hormones, gastrin and cholecystokinin (CCK), display four molecular characteristics. 1) Homology. Sequences of the primary structures are identical. Because the identity comprises the active site, the homology is functionally important. The homology reflects evolution from a common ancestor. 2) Heterogeneity. Each hormone exists in different molecular forms in any single species. The heterogeneity comprises both variations in lengths of the polypeptide backbone, "macroheterogeneity," and derivatizations of single amino acid residues, "microheterogeneity." Both types of modification govern the biological potency. The heterogeneity reflects enzymatic modifications of the primary ribosomal translation product. 3) Ubiquity. Each hormone is synthetized in different cell types, which are localized in gastrointestinal as well as extra-gastrointestinal tissues. The cell type determines the route by which the active peptide(s) reaches its target, either via blood (endocrine secretion) or by local release (neurocrine and paracrine secretion). Inasmuch as all cells contain gastrin and CCK genes, the variable expression probably reflects differentiation in development of the posttranscriptional biosynthetic machinery. 4) Differential principality. In different tissues and cells, different molecular forms may predominate. Moreover, one form is more potent with respect to one effect (e.g., CCK-8 in relation to pancreatic exocrine secretion), whereas another form (CCK-4) is more potent with respect to another effect (pancreatic endocrine secretion). Together the differential principality and secretory routes (blood borne or local) ensure that gastrin and CCK peptides regulate their targets with optimal effect in spite of the heterogeneity and wide distribution, which otherwise might cause disturbing interactions and subsequent inefficacy. The key to a better understanding of the basis characteristics is knowledge about the evolution and expression of the structural gene(s) for gastrin and CCK. Acquisition of such knowledge will be of considerable value, since available evidence suggests that the gastrin-CCK system is a good model for general features of regulatory peptides.
 ...
PMID:Four basic characteristics of the gastrin-cholecystokinin system. 701 99

The gastrointestinal peptide cholecystokinin (CCK) has been shown to stimulate pancreatic growth in the adolescent and adult rat. However, little is known about the role of gastrointestinal hormones in the regulation of organ formation during fetal development. We therefore examined the effects of the CCK receptor antagonist devazepide (25 micrograms/h) and an antigastrin/CCK monoclonal immunoglobulin G on the maternal and fetal rat pancreas. These substances were infused subcutaneously with minipumps in female rats during the entire period of gestation. At the end of gestation, the rats were killed and the pancreata of the dams and their litter were examined for DNA and protein. In the dams, the receptor antagonist and the antibody against CCK/gastrin had no effect. In the newborns, the CCK receptor antagonist led to a significant reduction of the protein and DNA concentration [protein in controls, 105.0 +/- 3.75 micrograms/mg pancreatic tissue; in the antagonist group, 91.9 +/- 4.2 micrograms/mg pancreatic tissue (p < 0.05); DNA in controls, 1.28 +/- 0.19 micrograms/mg pancreatic tissue; in the antagonist group, 0.48 +/- 0.06 micrograms/mg pancreatic tissue (p < 0.05) (mean +/- SEM)]. Immune neutralization of CCK/gastrin in the maternal-fetal circulation induced a reduction of the protein concentration in the fetal pancreas (85.3 +/- 3.06 micrograms/mg pancreatic tissue; p < 0.01) but had no effect on fetal pancreatic DNA. Additional experiments indicated effective concentrations of the CCK receptor antagonist in fetal pancreatic tissue and free binding sites of the circulating antibody. In conclusion, the study provides evidence that CCK and its analogues are involved in fetal pancreatic organogenesis.
 ...
PMID:The role of CCK and its analogues in the organogenesis of the fetal rat pancreas. 762 5

The present study reports the first evidence that the gastrointestinal peptide gastrin stimulates the growth of several human pancreatic cancer cells in culture and in tumors transplanted to nude mice. Gastrin promoted growth of all cell lines tested at a dose comparable to the binding affinity, providing evidence for a physiologically relevant receptor. The stimulatory effects of gastrin were blocked by the CCK-B/gastrin receptor antagonist L-365,260 and not by the CCK-A receptor antagonist L-364,718. Growth of PANC-1 cells in culture were inhibited by L-365,260, suggesting that gastrin is tonically produced by PANC-1 cells for regulation of growth. Athymic nude mice bearing PANC-1 xenografts were treated for 24 days subcutaneously with either 1% bovine serum albumin (diluent), pentagastrin (1 mg/kg), or L-365,260 (1 mg/kg) twice daily. Tumors from the pentagastrin-treated mice were found to weigh more and have greater protein and DNA content than controls, whereas these values were all decreased in tumors of L-365,260-treated mice. Receptor binding capacity changed in tumors of animals treated with the peptide or antagonist, suggesting a regulatory process. Gastrin immunoreactivity was detected in a transplanted PANC-1 human tumor. These results identify gastrin as a potent trophic peptide that actively stimulates growth of human pancreatic cancer and does so through a CCK-B/gastrin-like receptor.
 ...
PMID:Identification of gastrin as a growth peptide in human pancreatic cancer. 784 Mar 13

The gastrointestinal peptide cholecystokinin (CCK) is known to stimulate growth of human pancreatic cancer in a receptor-mediated fashion. The purpose of this study was to characterize the receptor responsible for the trophic effects of CCK in cancer cells. With the use of homogenates of PANC-1 human pancreatic cancer cells grown in vitro, the binding characteristics and optimal conditions of radiolabeled selective CCK-receptor antagonists ([3H]L-365,260 and [3H]L-364,718) were examined. Specific and saturable binding was detected with [3H]L-365,260, and Scatchard analysis revealed that the data were consistent for a single site of binding with a binding affinity of 4.3 +/- 0.6 nM and a binding capacity (Bmax) of 283 +/- 68 fmol/mg protein in log phase cells. Binding was dependent on protein concentration, time, temperature, and pH and was sensitive to Na+, K+, Mg2+, and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. In contrast to log phase cells, Bmax decreased by 80 and 92% in confluent and postconfluent cultures, respectively. Subcellular fractionation studies revealed that binding was in the membrane fraction. Competition experiments indicated that L-365,260 and gastrin were more effective at displacing the radiolabeled L-365,260 than CCK. No binding was detected with the CCK-A antagonist [3H]L-364,718. Assays performed with [3H]L-365,260 on five additional human pancreatic cancer cell lines in vitro and tumor tissue from xenografts in nude mice also revealed specific and saturable binding. These results provide the first identification of a CCK-B/gastrin receptor in human pancreatic cancer cells and tumors and explain the effects of CCK on the growth of this malignancy.
 ...
PMID:Identification and characterization of CCK-B/gastrin receptors in human pancreatic cancer cell lines. 830 51

The gastrointestinal peptide cholecystokinin (CCK) has been shown to stimulate growth of human pancreatic adenocarcinoma in vitro and in vivo, although CCK receptors have not been identified in pancreatic cancer cells. The purpose of this study was to characterize the CCK receptors in pancreatic cancer cells and to correlate the receptor binding studies with the trophic action of CCK agonists and antagonists. With the use of homogenates of PANC-1 human pancreatic cancer cell line grown in culture, the binding of 125I-labeled CCK octapeptide (125I-CCK-8) was examined under various conditions to characterize the CCK receptor. Specific and saturable binding of 125I-CCK-8 was detected in PANC-1 cells; data were consistent with a single binding site. Scatchard analysis yielded a binding affinity [dissociation constant (Kd)] of 2.8 nM and a binding capacity of 26 fmol/mg protein. Binding was dependent on protein concentration, time, temperature, the presence of protease inhibitors, and pH and was sensitive to Na+, K+, Mg2+, and ethylene glycolbis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Competition experiments indicated that L-365,260, a selective CCK-B (gastrin) receptor antagonist, was the most potent displacer of 125I-CCK-8, and no significant displacement of binding was found with the selective CCK-A receptor antagonist. Growth of PANC-1 cells in culture was stimulated by CCK at a concentration consistent with the Kd, and CCK-stimulated growth was inhibited by the CCK-B receptor antagonist (L-365,260) not the CCK-A receptor antagonist (L-364,718).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cholecystokinin receptors and PANC-1 human pancreatic cancer cells. 833 63

During the last quarter of this century gastrointestinal endocrinology has grown explosively. In 1970, three hormones (secretin, gastrin, and cholecystokinin) were identified and by authorities in the field considered sufficient to explain the entire hormonal regulation of digestion. That was some underestimation. Today the gut is known to express more than 20 different hormonal/regulatory peptide systems. Their widespread cellular occurrence, gene expression cascades, secretory mechanisms, receptors and receptor binding, as well as normal and pathophysiological effects are now also fairly well known owing to the marked progress in basic sciences and biochemical technologies (immuno and peptides chemistry, molecular and cell biology). Thus, the gut is now recognized as the largest endocrine organ of the body; and a substantial part of the gastroenterologic research over the latest decades has been devoted to gut hormones. The following review describes the recent development, with emphasis on gastrointestinal peptide systems that have been studied and even discovered in Denmark. Hence, as reflected by the number of doctoral theses and PhD studies (> 50 since 1974), gastrointestinal endocrinology has been a major research area in this country in the past 25 years.
 ...
PMID:Gastrointestinal endocrinology. 872 76

The gastrointestinal peptide, gastrin, tonically stimulates growth of human colon cancer cells in vivo and in vitro, and does so in a receptor-mediated fashion. This study defined the nature of gastrin binding in human colon cancer using [3H]L-365,260, a specific cholecystokinin B (CCK-B)/gastrin antagonist found to block gastrin's effects on growth. Following elucidation of optimal binding conditions (e.g., pH, time, and temperature) in log phase HT-29 human colon cancer cells, specific and saturable binding with a dissociation constant of 4.8 +/- 0.7 nM and a maximal binding capacity (Bmax) of 320 +/- 120 fmol/mg protein, consistent with a single binding site, was recorded. Binding was localized to the membrane fraction. Exposure to gastrin or receptor antagonist decreased and increased, respectively, the Bmax. Competition experiments indicated that L-365,260 was 25- and 200-fold more effective at displacing radiolabeled L-365,260 than gastrin and cholecystokinin, respectively. In contrast to log phase cells, the Bmax was decreased by 67 to 76% in confluent and postconfluent cultures. Binding activity was observed in other cell lines examined, as well as in xenografts and colon cancers obtained at surgery. Binding in normal human colonic mucosa was 10-fold less than in colon cancer. These results provide the first comprehensive identification and characterization of a CCK-B/gastrin-like receptor in human colon cancer.
 ...
PMID:Characterization of the CCK-B/gastrin-like receptor in human colon cancer. 885 5

We have previously demonstrated that endogenous ascorbic acid is secreted into the gastric lumen by cholinergic stimulation in both conscious pylorus-ligated rats and the perfused stomach of unconscious rats, and that gastrin, a potent gastric stimulatory peptide hormone, has no effect. In the present study, the effects of some gastrointestinal peptide hormones on gastric ascorbic acid secretion were further examined in the perfused stomach of rats. An intravenous administration of cholecystokinin octapeptide (CCK-8) significantly increased gastric ascorbic acid secretion at a dose of 1.0 and 4.0 micrograms/kg, whereas the other three peptides examined, bombesin, neurotensin and substance P, showed no or little effect at the doses which were quite commonly employed for evaluation of various gastric functions. CCK-8-induced ascorbic acid secretion was reduced by pretreatment with proglumide, which is a CCK receptor antagonist, but not by pretreatment with atropine. These results indicate that gastric ascorbic acid secretion is physiologically regulated not only by muscarinic receptor-associated cholinergic stimulation but also by CCK receptor-associated humoral stimulation.
 ...
PMID:Cholecystokinin stimulates ascorbic acid secretion through its specific receptor in the perfused stomach of rats. 982 Dec 9

A review is presented on quantitative structure-activity relationship (QSAR) studies on cholecystokinin antagonists. Cholecystokinin (CCK) is a gastrointestinal peptide hormone closely related chemically to gastrin. However, its receptors are found in both peripheral and central nervous systems. Those present in peripheral system have been termed as CCK-A receptors and those present in central nervous system as CCK-B receptors. QSAR studies verify that CCK-B receptors are closely related structurally to gastrin receptors. QSAR studies have been reported on different classes of CCK antagonists, e.g., benzodiazepine derivatives, amino acid derivatives, quinazolinones, and peptides and pseudopeptide analogs. These QSAR studies unravel the mechanisms of interactions of each category of antagonists with the CCK receptors. In the case of benzodiazepines, the hydrophobic interactions and hydrogen bondings are found to be the most important binding force, while in the case of quinazolinones, only the hydrogen bonding is found to be important. The hydrophobic as well as the dispersion interactions are shown to be important for the binding of glutamic acid analogs and steric factors appear to govern the activity of peptides and pseudopeptide analogs.
 ...
PMID:Quantitative structure-activity relationship studies on cholecystokinin antagonists. 1181 53


<< Previous 1 2 3 4 Next >>