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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Porcine vasoactive intestinal peptide stimulated adenosine 3':5'-monophosphate (cyclic AMP) production in rat intestinal epithelial cells. The stimulation was dependent on time and temperature and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Under optimal conditions (at 15 degrees C, with 0.2 mM 3-isobutyl-1-methylaxanthine, at a cell concentration up to 18 microgram DNA/ml), the cyclic AMP production produced by vasoactive intestinal peptide was constant for 10 min and stopped after 15 min incubation, at either low (1 nM) or high (30 nM) concentration of the peptide. This plateau effect was demonstrated not to be due to an inactivation of vasoactive intestinal peptide in the medium nor to an alteration of receptors for the peptide. Cyclic AMP production was sensitive to a concentration as low as 0.1 nM vasoactive intestinal peptide. Maximal stimulation of cyclic AMP levels by vasoactive intestinal peptide was observed with 30 nM vasoactive intestinal peptide and represented an 11-fold increased above basal. The dorse-response curve was monophasic with a Km of 2.3 x 10(-9) M. No cooperative effects were detected by Hill analysis. The positive non-linear relationship observed between stimulation of cyclic AMP production and occupancy of binding site was not time-dependent as indicated by experiments performed after 15, 45 and 120 min incubation. Maximal and half-maximal responses were obtained at about 70% and 7% occupation of binding sites, respectively. Chicken vasoactive intestinal peptide and porcine secretin were agonists of porcine vasoactive intestinal peptide with a 6-times and a 120-times lower potency, respectively. Among secretin analogs that were found to have low affinity for vasoactive intestinal peptide binding sites, [4-alanine, 5-valine]secretin, that resembles vasoactive intestinal peptide at the first seven amino acids at the N-terminal end, was a partial agonist of vasoactive peptide at the first seven amino acids at the N-terminal end, was a partial agonist of vasoactive intestinal peptide and others failed to stimulate cyclic AMP production. Glucagon (10microM), gastric inhibitory peptide (0.1 microM), substance, P, neurotensin, octapeptide of cholecystokinin, bovine pancreatic polypeptide, human gastrin I with leucine at residue 15, Leu-enkephalinand somatostatin (1 microM) did not alter cyclicAMP levels. Non-peptide mediators such as dopamine, serotonin, acetylcholine and histamine, tested at 10 microM, were also ineffective. Prostaglandins E2, E1 and isoproterenol, tested at 10 microM, induced an increase of cyclic AMP levels above basal but were 9.5, 13.7 and 17.5 times less efficient than vasoactive intestinal peptide, respectively. Thus vasoactive intestinal peptide is a unique stimulus of cyclic AMP production in rat intestinal epithelial cells.
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PMID:Interaction of vasoactive intestinal peptide with isolated intestinal epithelial cells from rat. 2. Characterization and structural requirements of the stimulatory effect of vasoactive intestinal peptide on production of adenosine 3':5'-monophosphate. 8 68

The relationship between cyclic AMP production and the response of isolated canine parietal cells to histamine has been examined. Histamine increased cyclic AMP generation, and this effect correlated with histamine stimulation of oxygen consumption and aminopyrine accumulation. Metiamide inhibited histamine-stimulated cyclic AMP generation and oxygen consumption in a parallel fashion. At concentrations below 100 microM, isobutyl AMP production and oxygen consumption in a similar fashion. However, with IMX above 100 microM, histamine caused no further increases in oxygen consumption, despite markedly enhanced cyclic AMP generation. Neither carbachol nor gastrin increased cyclic AMP production beyond that produced by IMX alone, and the combinations of histamine and carbachol and of histamine and gastrin produced no greater cyclic AMP generation than produced by histamine. These findings support a close relationship between cyclic AMP production and the action of histamine but not of carbachol or gastrin on isolated parietal cells. The mechanisms underlying the potentiating interactions between histamine, carbachol, and gastrin involve step(s) beyond stimulation of cyclic AMP generation.
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PMID:Histamine and cyclic AMP in isolated canine parietal cells. 9 22

Two isoenzymes of carbonic anhydrase, one with high activity and the other with low activity, were isolated from rat gastric tissue. It was found that both isoenzymes were phosphorylated in vitro by protein kinase isolated from gastric mucosa and that this process was stimulated by 3',5'-AMP. The phosphorylation of highly active carbonic anhydrase isoenzyme is shown to result in the increase of its activity. The phosphorylation of low active carbonic anhydrase isoenzyme did not affect its activity or decreased it slightly. The results obtained suggest that the activation of carbonic anhydrase in vivo by gastrin (pentagastrin), histamine and 3',5'-AMP is due to the phosphorylation of highly active isoenzyme by 3',5-AMP-dependent protein kinase. It seems possible that in this process histamine and 3',5'-AMP act as sequential mediators of pentagastrin effect.
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PMID:[Activation of carbonic anhydrase from rat gastric tissue as a result of phosphorylation by 3',5'-AMP-dependent protein kinase]. 17 24

In the presence of 5 mM theophylline, secretin and vasoactive intestinal peptide (VIP) each increased cyclic adenosine 3':5'-monophosphate (cyclic AMP) in acinar cells isolated from guinea pig pancreas. Without theophylline, neither peptide altered cellular cyclic AMP. Glucagon, which is similar to secretin and VIP both in chemical structure and spectrum of biologic activities, neither stimulated cellular cyclic AMP nor inhibited the stimulation produced by secretin or by VIP. Other agents which were tested and found not to increase cellular cyclic AMP were cholecystokinin, carboxyl-terminal octapeptide of cholecystokinin, gastrin I, gastrin II, bovine pancreatic polypeptide, carbamylcholine, and prostaglandin E1. Neither carboxyl-terminal octapeptide nor gastrin I altered the stimulation of cellular cyclic AMP produced by secretin or VIP. With natural secretin a significant increase in cellular cyclic AMP could be detected at concentrations as low as 3 x 10(-10) M and maximal stimulation occurred at 10(-8) M. VIP was approximately 1% as potent as natural secretin and maximal concentrations of secretin plus VIP increased cellular cyclic AMP to the same value as was obtained with a maximal concentration of secretin alone.
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PMID:Cyclic AMP in pancreatic acinar cells: effects of gastrointestinal hormones. 17 15

The presence and development of immunoreactive gastrin (IRGa) in the fetal and neonatal pancreas and pyloric antrum of the rat were studied. IRGa appeared in both organs at least as early as the 16th day of fetal life. Antral IRGa increased rapidly and continuously in the neonatal period, while pancreatic IRGa concentration increased and was maintained at a relatively constant level from days 5 to 35. Monolayer cell cultures of the neonatal rat pancreas were used to evaluate the role of cyclic AMP mediated release of gastrin. The addition of N6,O2'-dibutyryl cyclic AMP (4 mM) or theophylline (4 mM) to the culture medium induced significant release of gastrin. The stimulation of adenylate cyclase with cholera toxin (10 ng/ml) also resulted in significant gastrin release. Long-term cultures (18-24 days) were shown to release gastrin continuously at a relatively constant rate. The cellular localization of pancreatic gastrin in 7-day-old cultures was performed by immunological techniques, using fluorescein-labeled antibodies to gastrin. The gastrin-containing cells were located at the periphery of most of the endocrine cell clusters. Immunofluorescence techniques for insulin and glucagon also showed that the alpha cells had a similar peripheral distribution, although they were more frequent in number. In contrast, insulin-containing cells were numerous and were present in all areas of the endocrine cell clusters. The studies support the following conclusions: a) Gastrin is present in the rat pancreas, even as early as late fetal life; b) Gastrin-producing cells are present and functionally competent in monolayer cell cultures of the neonatal rat pancreas for prolonged periods of time (24 days); c) Gastrin is released from these cells when intracellular levels of cyclic AMP are increased; d) By immunofluorescence methods, the gastrin-producing cells in pancreatic cell cultures are found to be located at the periphery of the endocrine cell clusters.
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PMID:Gastrin in the perinatal rat pancreas and gastric antrum: immunofluorescence localization of pancreatic gastrin cells and gastrin secretion in monolayer cell cultures. 18 64

We tested the radioassays for cyclic AMP and human gastrin, both involving separation on coated charcoal, for interaction with bile acids and detergents, and found a concentration-dependent interaction of taurocholic and glycocholic acid as well as of the surfactant Triton X-100 and sodium laurylsulfate in both assays. The interaction was detectable from concentrations of 0.5 mmol of bile acid per liter or 625 mg of detergent per liter, giving rise to falsely decreased gastrin values and falsely increased or decreased values for cyclic AMP. The interactions demonstrated may be a general effect on all radioassays that are based on the use of coated charcoal in the separation of free from bound ligands.
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PMID:Bile acid and detergent interaction with radioassays based on coated charcoal. 18 82

To evaluate whether cyclic nucleotides play a role as mediators in antral gastrin release, the following in vivo experiments were performed in dogs. An antral pouch was constructed and the rest of the stomach, the pancreas and small and large intestine were resected. A gastric artery supplying the pouch was cannulated, and after a basal period with saline infusion either dibutyryl cyclic 3',5'-adenosine monophosphate (cyclic AMP, 0.2 mg per kg per min), dibutyryl cyclic 3',5'-guanosine monophosphate (cyclic GMP, 0.05 mg per kg per min) or saline were infused over a period of 60 min. To prove the viability of the pouch and to show its ability to release gastrin with proper stimulation, bethanechol chloride (urecholine) was infused into the gastric artery at the end of the experiment. Blood samples were taken from the portal vein and assayed for gastrin. Neither cyclic AMP nor cyclic GMP infusion was found to increase portal gastrin concentration to a significant degree. A marked increase in portal gastrin concentration however, was observed when bethanechol chloride was infused. These studies lend no support to the thesis that cyclic nucleotides mediate gastrin release in the dog.
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PMID:Neither cyclic AMP nor cyclic GMP appear to mediate antral gastrin release in the dog. 19 40

The purpose of the present study was to examine stimulation of gastrin release and the synthesis of gastrin directly by measurement of incorporation of [(3)H]tryptophan into gastrin in rat antral mucosal explants maintained in organ culture. Gastrin synthesis and secretion were assessed simultaneously at intervals over the 24-h duration of explant culture. Antral mucosal explants from fed female Wistar rats (4-5 wk, 100-150 g) were cultured at 37 degrees C (95% O(2)/5% CO(2)) in medium containing 70% Trowell-T8 and 10% NCTC-135 without unlabeled tryptophan, 10% dialyzed fetal calf serum and [(3)H]tryptophan (100 muCi/ml). Antral tissue was harvested at regular intervals during 24-h culture periods. Incorporation of [(3)H]tryptophan into immunoreactive gastrin was determined by techniques utilizing double-antibody immunoprecipitation. Antral tissue protein synthesis was assessed by measurements of incorporation of [(3)H]tryptophan into tissue protein of cultured antral explants. In paired experiments, gastrin synthesis and secretion in the presence of dibutyryl cAMP (DBCAMP) were compared to those observed under control conditions. Gastrin and protein specific activity progressively increased with time. Gastrin specific activity at 30 min increased from 3.3+/-0.5 (SEM) to 55.2+/-10.6 fmol [(3)H]tryptophan/pmol gastrin (or from 1.57+/-0.48 to 26.28+/-5.05 pmol [(3)H]tryptophan/mug gastrin) at 24 h: specific activity of antral tissue protein at 30 min increased from 33.6+/-8.4 to 1,660+/-236 fmol [(3)H]tryptophan/mug protein at 16 h. Culturing of explants for 4 h in the presence of cycloheximide (100 mug/ml) inhibited both gastrin synthesis and protein synthesis by greater than 90 and 95%, respectively. DBCAMP (10 mM) significantly increased both the synthesis and secretion of antral gastrin when compared with control cultured explants. Results of these experiments provide direct demonstration of gastrin synthesis by rat antral mucosal explants in organ culture, indicate that both gastrin and total antral protein synthesis are inhibited by cycloheximide, and demonstrate DBCAMP-induced stimulation of both gastrin synthesis and secretion, suggesting the potentially important role of cyclic AMP in gastrin cell function.
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PMID:Stimulation of gastrin secretion and synthesis in antral organ culture. 19 22

Tissue culture methods were used to study the gastrin-producing cells isolated from the pyloric antral mucosa of rats. Cultures were maintained for up to 7 days. Gastrin cells were identified by means of immunofluorescent and unlabeled antibody-enzyme techniques. The tissue culture medium was monitored for basal gastrin secretion. In addition, stimulation of gastrin release was achieved by the use of dibutyryl cyclic-AMP and theophylline. This is the first report of the successful application of tissue culture methods to the functional study of antral gastrin cells. The procedure has proven to be useful in assessing the mechanisms of gastrin secretion.
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PMID:The gastrin-producing cells in tissue cultures of the rat pyloric antrum. 19 6

In female rats aspirin-induced gastrin mucosal damage was increased and glycoprotein synthesis decreased by fasting and by insulin administration. Glucose added to the drinking water during the fasting period reduced mucosal damage and increased glycoprotein synthesis to control levels. Alloxan diabetes did not affect mucosal damage or glycoprotein synthesis. Alloxan diabetes plus insulin restored blood glucose levels to normal, and susceptibility to aspirin damage and glycoprotein synthesis were also normal. Alloxan diabetes plus fasting restored blood glucose levels to normal but increased aspirin-induced mucosal damage and reduced glycoprotein synthesis. In vitro incubation of gastric mucosal homogenates showed that diburyryl cyclic AMP and theophylline inhibited glycoprotein synthesis but dibutyryl cyclic GMP had no significant effects. The importance of an adequate supply of glucose to the gastric mucosa and the effects of cyclic nucleotides on glycoprotein synthesis are discussed.
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PMID:Effects of blood glucose levels on aspirin-induced gastric mucosal damage. 20 Jan 38


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