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)

In rats given a copper-deficient diet plus penicillamine to destroy the acinar tissue selectively, the sensitivity and secretory pattern of pancreatic duct cells to a variety of hormones has been investigated. Resting flow rate of this pancreatic duct model was in the same range as in the intact gland. The duct cells responded to increasing doses of secretin by producing more juice with increasing outputs of bicarbonate, sodium, potassium, and chloride. Bicarbonate concentration increased with the lowest dose of secretin up to values of 64 mEq per liter and did not further increase with higher doses of secretin and increasing secretory rates. The concentration of potassium increased with increasing doses of secretin and flow rates, whereas chloride concentration decreased in a reciprocal fashion to bicarbonate. Gastrin and cholecystokinin-pancreozymin did not significantly stimulate the duct cells. Atropine did not inhibit the action of secretin on the flow rate or on bicarbonate secretion.
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PMID:Pancreatic duct cells in rats: secretory studies in response to secretin, cholecystokinin-pancreozymin, and gastrin in vivo. 90 83

Binding of 125I-[Nle15]gastrin to albumin purified from porcine serum, from porcine gastric mucosal cytosol, and from bovine serum has been demonstrated by covalent cross-linking and ultracentrifugation. Binding was enhanced in the presence of Zn2+, Ni2+, Cu2+, Co2+, and Cd2+, but not Ca2+, Mg2+, or Mn2+. The best fit to the binding data for bovine serum albumin was obtained with a model assuming two nonequivalent binding sites. The affinity of both sites for gastrin was increased in the presence of 100 microM Zn2+ or Ni2+ ions. The highest association constant observed was 2.3 X 10(5) M-1 in the presence of 100 microM Zn2+ ions. The similarity of the Zn(2+)-dependence of binding for bovine and porcine serum albumins, despite the replacement of His3 by Tyr, suggested that the N-terminal metal ion-binding site was not involved. Although all gastrin affinities were reduced by 50% in the presence of 150 mM NaCl, the Zn(2+)-dependence of binding was retained. We therefore propose that the ternary complex of gastrin, Zn2+ ions, and albumin may play a physiological role in the serum transport of Zn2+ ions and in the uptake of Zn2+ ions from the lumen of the gastrointestinal tract.
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PMID:Metal ion-dependent binding of gastrin to albumin. 195 45

As is the case with many other peptide hormones of the brain and intestine, the formation of biologically active gastrin from a glycine-extended processing intermediate occurs via the action of a peptidylglycyl alpha-amidating monooxygenase (PAM). The observation that gastrin exists primarily as unamidated precursors in the pituitary but as amidated gastrin in the antrum prompted this study to examine whether the amidating enzymes in the two organs were different in their characteristics. Amidating activity was quantified by measuring the conversion of glycine-extended tridecagastrin (G13-Gly) to amidated tridecagastrin and glycine-extended hexapancreatic polypeptide (PP6-Gly) to amidated hexapancreatic polypeptide by radio-immunoassay. Two molecular forms of amidating activity were identified in both the porcine antrum and pituitary. The first, PAM-A, had an apparent Mr of 51,000 and a net negative charge at pH 7.0, whereas PAM-B was smaller (Mr approximately 30,000) and had a net positive charge at pH 7.0. Both molecular forms were similar in their cofactor requirements (copper, ascorbic acid, and catalase) and pH optima in the antrum and pituitary. The Km was significantly lower and the Vmax higher for PP6-Gly than for G13-Gly in the pituitary and antrum. These data suggest that although there is no difference between antral and pituitary PAM, the selective affinity of PAM for certain substrates may provide a mechanism for the differential amidation of different hormones within a given tissue or cell.
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PMID:Gastrin-amidating enzyme in the porcine pituitary and antrum. Characterization of molecular forms and substrate specificity. 198 4

Formation of biologically active amidated gastrin from glycine-extended progastrin processing intermediates (G-Gly) is achieved via the action of peptidyl-glycyl alpha-amidating monooxygenase. Since this enzyme requires copper for optimal activity, we examined the effects of a known copper chelator, diethyldithiocarbamate (DDC), on gastrin posttranslational processing and gastric acid secretion in vivo. DDC (400 mg.kg-1.day-1 ip X 3 days) administered to male Sprague-Dawley rats decreased antral amidated gastrin content, but increased antral G-Gly content. The ratio of amidated gastrin to G-Gly, which reflects in situ amidating activity, was decreased in DDC-treated rats. In contrast, tissue amidating potential, assayed directly under optimal copper concentrations in vitro, was increased in the antrum and unchanged in the pituitary. DDC markedly increased both basal and gastrin-stimulated gastric acid outputs despite the presence of normal serum amidated gastrin levels. These results suggest that copper chelation with DDC inhibits amidating activity in situ but selectively increases antral amidating enzyme synthesis. The marked increase in acid secretion despite normal circulating amidated gastrin concentrations, combined with the enhanced secretory response to exogenously administered gastrin, suggests the possibility that gastrin receptors are upregulated by the events precipitated via DDC administration.
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PMID:Inhibition of the alpha-amidation of gastrin: effects on gastric acid secretion. 215 43

The influence of gastrin alpha-amidation of the heavy-metal chelator diethyldithiocarbamate and disulfiram, its disulfide dimer, was studied in rat gastric antrum. Sensitive, sequence-specific immunoassays for glycine-extended and amidated gastrin were used to monitor extractions and chromatography. The results showed that intraperitoneal diethyldithiocarbamate administration (1000 mg/kg body weight) for two days caused a decrease in amidated gastrin from 2.6 +/- 0.4 to 1.4 +/- 0.3 nmol/g tissue (n = 11) with a simultaneous increase in glycine-extended gastrin from 0.84 +/- 0.15 to 2.4 +/- 0.3 nmol/g. Peroral administration of disulfiram (4 mg/kg body weight) for nine days did not change alpha-amidation significantly. The results of the present study demonstrate that the heavy-metal chelating agent diethyldithiocarbamate inhibits alpha-amidation of gastrin in vivo, in agreement with the inhibition of amidating activity observed in vitro. These results are in accordance with the previous observations that the presence of copper ions is necessary for the alpha-amidation to take place.
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PMID:Alpha-amidation of gastrin is impaired by diethyldithiocarbamate. 217 Oct 44

The formation of biologically active gastrin from glycine-extended processing intermediates occurs via the action of a peptide alpha-amidating enzyme. The observation that gastrin exists primarily as unamidated precursors in the pituitary but as amidated gastrin in the antrum prompted these studies to examine whether the amidating enzymes in the two organs were different in their characteristics. Furthermore, the amidating enzyme in the stomach has not previously been characterized in extensive detail. Amidating activity was quantified by measuring the conversion of Tyr-Gly-Trp-Met-Asp-Phe-Gly (glycine-extended hexagastrin) to Tyr-Gly-Trp-Met-Asp-Phe-NH2 (amidated hexagastrin) by radioimmunoassay. The activity of the antral enzyme in both the rat and hog had a similar apparent molecular weight (45,000-60,000), cofactor requirements (copper, ascorbic acid, and catalase), pH optima (5.5-8.5), and Km (12 microM) as the pituitary enzyme. These data suggest that antral and pituitary peptide alpha-amidating enzymes are the same enzyme, thus it is unlikely that differences in amidating enzymes can account for the observed differences in the tissue specific processing of gastrin.
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PMID:Characterization of gastrin amidation in the rat and porcine antrum: comparison with the pituitary. 234 64

Intestinal adaptation has been studied in rats with pancreatic atrophy induced by feeding a copper-deficient diet and penicillamine and in rats with carbohydrate maldigestion induced by feeding of an alpha-glucosidase inhibitor (acarbose). Pancreatic atrophy led to a significant increase of weight, protein, and DNA content as well as specific activities and total amounts of the enzymes sucrase and maltase in the distal but not in the proximal part of the small intestine. Plasma levels of CCK and GIP were significantly higher in rats with pancreatic atrophy, whereas plasma levels of gastrin and insulin were lower. Tissue concentrations of gastrin in the antrum and GIP in duodenum and jejunum were unchanged. Duodenal CCK and jejunal substance P, somatostatin, and VIP and ileal substance P and somatostatin were significantly decreased in rats with acinar atrophy. Glucosidase inhibition by acarbose feeding led to weight increase of the small intestine and cecum. This was more marked when acarbose was fed together with a fiber-free diet. Under these conditions the protein and DNA content also increased significantly in both gut segments and maltase and sucrase content predominantly in the distal part. Insulin plasma concentration decreased significantly in the acarbose-fed groups, whereas GIP, gastrin, and CCK plasma concentrations remained unchanged. After fiber-rich diet tissue concentrations of gastrin in the antrum and insulin in the pancreas were significantly higher and GIP concentrations in the duodenum and jejunum significantly lower than after fiber-free diet. Acarbose increased the pancreatic insulin concentration only in the fiber-free group and did not influence gastrin and GIP concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adaptation of the small intestine to induced maldigestion in rats. Experimental pancreatic atrophy and acarbose feeding. 389 54

Rats were fed with a copper-deficient diet combined with penicillamine to produce an atrophy of the exocrine pancreas by selective destruction of the acinar cells, which are replaced by fat cells. Plasma cholecystokinin (CCK) concentrations in animals with exocrine pancreatic atrophy were 250% higher compared to control animals (21.7 +/- 7.8 vs. 6.1 +/- 1.07 pmol/l; p less than 0.001). Plasma concentrations of gastrin were significantly decreased by 44% and of gastric inhibitory polypeptide (GIP) significantly increased by 24%, while the decrease of the plasma insulin did not reach the level of significance. In the proximal duodenum a significant decrease of the CCK concentration could be observed, whereas tissue concentrations of GIP in duodenum and jejunum and gastrin in the gastric antrum remained unaltered. These data suggest that the negative feedback control of pancreatic enzyme secretion is mediated by the release of CCK.
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PMID:Elevated plasma cholecystokinin concentrations in exocrine pancreatic atrophy in the rat. 637 66

The complained gastrointestinal symptoms in PSS are probably caused by several complex disturbances like intestinal transit disturbances (ITD), bacterial overgrowth of the small intestine caused malabsorption of bile acids and altered kinetics of intestinal hormones. 25 patients with PSS and eleven healthy controls were tested for the existence of ITD by use of the metal-detector test (MDT). Twelve patients were also tested for a malabsorption of primary bile acids by radioimmunological measurement of clolylglycine serum levels before and after a meal. In addition serum concentrations of gastrin (nine patients) and plasma concentrations of cholecystokinin (CCK) (eight patients) and motilin (eleven patients) were measured by radioimmunoassay pre- and postprandial. Interdigestive gastric emptying was accelerated in patients with PSS (53 +/- 3 min. vs. 73 +/- 7 min.; p<0.01). Small intestinal transit times were similar in both groups (115 +/- 17 min. vs. 121 +/- 13 min.). Colonic transit in patients with PSS was significant prolonged (63 +/- 6 h vs. 39 +/- 5 h; p<0.05). There were no significant differences between the two groups concerning the pre- and postprandial levels of cholylglycin. Basic and postprandial levels of gastrin, CCK and motilin were higher in the PSS group. In contrast to scintigraphic studies using semisolid meals gastric emptying of the copper pellet in PSS was accelerated. A general malabsorption of primary bile acids was not found. Prolonged colonic transit times correlate well with frequently complained obstipation. Gastric hypacidity could be the reason of elevated gastrin levels. The high motilin-levels in PSS could be due to a lack of the feed-back inhibition as a result of diminished phase-III activity of the interdigestive migrating motor complex. The elevation of CCK-levels could reflect compensation of neurogenic or myogenic disturbances of gallbladder contraction.
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PMID:[Gastrointestinal involvement in progressive systemic scleroderma]. 860 Jun 62

In single, superfused, FURA-2AM loaded insulin producing HIT-T15 cells, gastrin releasing peptide (GRP) induced a peak in cytoplasmnic Cu2+ ([Ca2+]i) followed by a sustained (high GRP concentrations) or oscillatory (low GRP concentrations) [Ca2+]i pattern. The GRP (25-50 microM)-induced [Ca2+]i oscillations ceased upon removal of glucose or addition of thapsigargin (1 microM), EGTA (2 mM), or diazoxide (200 microM), whereas nifedipine (10 microM) reduced their amplitude (by 35%). Both protein kinase C (PKC)-activation or PKC-inhibition disrupted GRP induced [Ca2+]i oscillations. GRP induced [Ca2+]i oscillations in insulin producing cells therefore rely on intracellular Ca2+ mobilization, voltage-dependent and voltage-independent Ca2+ entry mechanisms and the integrity of protein kinase C.
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PMID:Cytosolic Ca2+ oscillations by gastrin releasing peptide in single HIT-T15 cells. 1046 9


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