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)

Key components of the mucous gel include the glycoprotein mucin and surface-active phospholipids. In the present study, mucin production and release of the surface-active phospholipid phosphatidylcholine (PC) into the medium were measured with an isolated canine mucous cell culture system. Stimulation of glycoprotein synthesis in response to 10(-4) mol/L histamine (160% +/- 9% of control, P < 0.01), 10(-6) mol/L gastrin (129% +/- 7%, P < 0.01), and 10(-6) mol/L carbamylcholine (129% +/- 7%, P < 0.01) was observed by metabolic labeling, whereas prostaglandin E2 (PGE2) had no effect. The effect of histamine was blocked by the H2 receptor antagonist cimetidine but not the H1 receptor antagonist diphenhydramine (P < 0.01). Activators of adenylate cyclase and cyclic adenosine monophosphate analogs significantly stimulated mucin synthesis (P < 0.05). A 7.8% +/- 1.7% increase in mucin above basal levels after 24 hours was observed with a solid-phase immunoassay in control wells, whereas histamine, gastrin, and carbamylcholine increased total mucin by 14% +/- 0.7%, 17% +/- 4.3%, and 20.4% +/- 4%, respectively (all P < 0.01), and PGE2 had no significant effect. PC release was stimulated by the administration of histamine, carbamylcholine, gastrin (108%-110% of control, P < or = 0.05), and PGE2 (120% of control, P < 0.01). The acid secretagogues histamine, gastrin, and carbamylcholine stimulated mucin synthesis and PC release. PGE2 has no direct role in the synthesis of canine gastric mucin but stimulates release of surface-active phospholipids. The mechanisms responsible for acid secretion provide for the coordinated production of the primary layer of defense against the injurious effects of low pH.
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PMID:Regulation of canine gastric mucin synthesis and phospholipid secretion by acid secretagogues. 850 Jul 55

The effects of tetragastrin on mucus glycoprotein (mucin) metabolism and mucosal protection in rat gastric mucosa were investigated. Rats were administered with various doses of tetragastrin (12, 120, or 400 micrograms/kg body weight; s.c.), followed by 50% ethanol-induced gastric injury. Tetragastrin caused a significant increase in mucin content in the corpus mucosa and prevented 50% ethanol-induced gastric mucosal damage in a dose-dependent manner. For assessment of the effects of tetragastrin on the metabolism of gastric mucin in detail, changes in mucin distribution in the three different layers of rat gastric mucosa were examined one hour after single administration of tetragastrin. A significant increase in the mucin content was noted in the mucus gel and surface mucosal layer. Mucin content in the deep mucosa corresponding mainly to the mucus neck cell mucin underwent virtually no change by this treatment. An increase in mucin in the mucus gel and surface mucosa would thus appear due to the administration of tetragastrin and may possibly be related to the protective action of the gastric mucosa against injury. The data demonstrate a possibility that gastrin may have potential for enhancing gastric mucosal protection associated with mucus secretion and/or mucus synthesis on the surface mucosa of rat gastric mucosa.
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PMID:Effects of tetragastrin on mucus glycoprotein in rat gastric mucosal protection. 138 48

In order to establish the measurement of gastric mucin secreted from cultured mucous cells, rat gastric mucin was purified from secreted mucus with Sepharose CL-4B column chromatography. Gastric mucin was measured by dot blot analysis using an enzyme-linked lectin (soybean agglutinin) assay in a good concentration-dependent manner. Surface epithelial cells were dispersed by limited digestion of a rat everted stomach and collected by density gradient centrifugation with Percoll. These cells were inoculated onto gelled collagen dishes, then cultured in a medium supplemented with 10% fetal calf serum under a 5% CO2 atmosphere in air. Changing the medium after a 2-d culture, the cells were cultured for another 3 d. During the culture, the numbers of cells each day were almost equal, but mucin contents in the cells increased, and then dropped at day 5 after inoculation. At that time, the edge of the cell layer peeled off and the cells adhered to each other. Using 2-d cultured cells, the effects of some secretagogues on mucin secretion were investigated. Carbachol, secretin, CCK-8 and prostaglandin E2 (PGE2) strongly stimulated mucin secretion, and gastrin I weakly did. However, histamine offered no stimulation.
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PMID:Gastric mucin secretion from cultured rat epithelial cells. 917 25

Infection with Helicobacter pylori (H. pylori) is now recognized as a major factor in the pathogenesis of gastric disease, and the successful therapy regimens require a combination of H2 blockers with gastroprotective and antimicrobial agents. Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene) amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is the only drug combining acid-suppressant activity with remarkable gastroprotective and anti-H. pylori properties. The drug not only displays a potent anti-H. pylori activity alone, but also exerts a strong potentiating effect on the efficacy of antimicrobial agents commonly used for H. pylori eradication, and the successful ulcer therapy with ebrotidine induces a significant (4-fold) increase in the H. pylori aggregation titer of gastric mucin. Moreover, the drug exhibits a strong inhibitory effect on H. pylori urease activity, the extent of which exceeds that of ranitidine, omeprazole and lansoprazole. Ebrotidine has also been demonstrated to exert a potent inhibitory action on the enzymatic activities directed towards mucus perimeter of gastric mucosal defense, causing a marked inhibition of H. pylori protease, lipase and phospholipase A2 activities. Another important property of ebrotidine is its ability to efficiently counteract the disruptive effects of H. pylori lipopolysaccharide on the integrity of gastric epithelium. This includes countering the interference by the lipopolysaccharide in mucosal integrin receptor interaction with proteins of extracellular matrix and the reversal of H. pylori disruptive effect on the binding of mucin to its gastric epithelial receptor. Furthermore, most recent data indicate that ebrotidine has the ability to reverse the impairment caused by H. pylori in feedback inhibition of gastrin release by somatostatin. This activity of ebrotidine apparently stems from the drug's ability to counter the untoward effect of H. pylori on the binding of somatostatin to its specific receptor on the gastric mucosal G-cells. The unique combination of acid suppressant, gastroprotective and anti-H. pylori activities makes ebrotidine a drug of choice in the treatment of gastric disease caused by H. pylori.
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PMID:Anti-Helicobacter pylori activities of ebrotidine. A review of biochemical and animal experimental studies and data. 920 47

Although gastrin, histamine, and carbachol (CCh) accelerate gastric mucin metabolism, information about their target cells of mucin production is lacking. To clarify this, we examined the effects of these stimulants, including the possible participation of nitric oxide (NO), on mucin biosynthesis in distinct sites and layers of rat gastric mucosa. Pieces of tissue obtained from the corpus and antrum were incubated in a medium containing radioactive precursors and each stimulant, with or without NO synthase (NOS) inhibitor. Distribution of NOS was compared with that of the specific mucins by immunostaining using specific antiserum and monoclonal antibodies. In the full-thickness corpus mucosa, tetragastrin enhanced [3H]glucosamine incorporation into mucin but had no effect on [14C]threonine incorporation. Both histamine and CCh dose dependently increased 3H- and 14C-labeled corpus mucin. Only CCh stimulated antral mucin biosynthesis. CCh stimulation was noted in the corpus mucosa after removal of surface mucous cells, but stimulation by tetragastrin or histamine disappeared as a result of this pretreatment. Only tetragastrin-induced activation was completely blocked by the NOS inhibitor. NOS immunoreactivity was limited to surface mucous cells. Mucus-producing cells present in the different sites and layers of the gastric mucosa have distinct mechanisms for regulation of mucin biosynthesis. Gastrin-stimulated mucin biosynthesis mediated by NO is limited to surface mucous cells of rat gastric oxyntic mucosa.
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PMID:Distinct effects of tetragastrin, histamine, and CCh on rat gastric mucin synthesis and contribution of NO. 945 83

Mucin biosynthesis is stimulated by gastrin during the process of glycosylation in the corpus mucosa of the rat stomach. The purpose of this study was to clarify, using an organ culture technique, whether biosynthetic responses to histamine in the rat gastric mucin are the same as that to gastrin. Radiolabeled mucin was obtained from the corpus and antral mucosa of the rat stomach after in vitro incubation for 5 h with [3H]glucosamine (GlcN), [14C]threonine (Thr), and [35S]sulfate. Addition of histamine (10(-7)-10(-5) M) to the culture medium increased [3H]GlcN-labeled mucin in the corpus tissue in a concentration-dependent manner. In the antrum, there was no significant change in the biosynthetic activity of mucin in response to histamine. Histamine at 10(-5) M also increased the incorporation of both [35S]sulfate and [14C]Thr into the corpus mucin. These results indicate that histamine stimulates the biosynthesis of the mucin peptide, as well as the glycosylation step in the corpus, and suggest that the effect of histamine on mucin synthesis is distinct from that of gastrin.
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PMID:Effects of histamine on mucin biosynthesis in rat gastric mucosa. 947 32

Although Helicobacter pylori infection increases gastrin secretion, it is unknown whether this is a direct effect or requires activation of the immune system. We developed an H. pylori-infected human primary antral epithelial cell culture model to address this question. This culture protocol favors growth of H. pylori, and infected cultures could be maintained for up to 48 h. These cultures were enriched for gastrin (10-40%), somatostatin (2-5%), and gastric mucin (60-80%) cells but did not contain immunocytes. Bacterial attachment occurred in a random manner within 2 h of infection, although bacterial density was lower than in sections from infected patients. After 24 or 48 h, the bacterial microcolonies were similar in size to those seen in vivo, and at 24 h ultrastructural studies demonstrated well-developed pedestal formation underlying the bacteria. Coculture with H. pylori increased basal but not stimulated gastrin secretion at all time points >2 h. In conclusion, a newly developed cell culture model has been used to characterize the interactions between H. pylori and normal human antral epithelial cells.
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PMID:Helicobacter pylori-infected human antral primary cell cultures: effect on gastrin cell function. 972 49

The effects of tetragastrin on gastric mucin biosynthesis in middle-aged rats were compared with those in young rats. The incorporation of [3H]glucosamine and [35S]sulfate into mucin was stimulated by tetragastrin in cultured corpus mucosa from 7-week-old rats. In contrast, tetragastrin could not enhance mucin biosynthesis in stomachs from 52-week-old rats. The isosorbide dinitrate-induced stimulation of corpus mucin biosynthesis observed in middle-aged rats was essentially the same as that seen in young rats. Nitric oxide (NO) synthase activity of the corpus was significantly reduced in the middle-aged rats compared to the young rats. NO synthase-immunoreactivity was observed at surface mucous cells in the corpus mucosa of young, but not of middle-aged, rats. These results suggest that aging decreases the effect of gastrin on gastric mucin biosynthesis through the age-related loss of NO synthase function in the surface mucous cell layer of rat stomach.
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PMID:Age-related stimulation by tetragastrin of gastric mucin biosynthesis in rat. 1006 56

The effect of L-365,260, a CCK-B/gastrin receptor antagonist, on gastric mucus metabolism induced by tetragastrin was investigated in rats. In vivo application of L-365,260 at a dose of 3 mg/kg p.o. significantly reduced the tetragastrin (12 microg/kg s.c. )-stimulated gastric acid secretion, but 0.3 mg/kg of L-365,260 did not affect the gastric acid secretion induced by the tetragastrin administration. A single administration of 12 microg/kg of tetragastrin caused an increase in gastric mucin content in the soluble mucus (175% of control), the mucus gel (155% of control) and the surface mucosa (125% of control). L-365,260 at the doses of 0.3 and 3 mg/kg considerably inhibited the tetragastrin-induced mucus secretion in the soluble mucus (70-80% of tetragastrin) and the mucus gel (45-70% of tetragastrin) and resumed the mucus accumulated in the surface mucosa to the control situation (80% of tetragastrin). In the in vitro incubation system of rat gastric mucosa, L-365,260 (0.1-10 micromol/l) caused no significant change in gastric mucin synthesis. An in vivo study also showed that the increase in total gastric mucin content and the distributional changes in mucin content induced by 12 microg/kg of tetragastrin reverted with 3 mg/kg of L-365,260 pretreatment to the control situation. It is evident from these results that the CCK-B/gastrin receptor is involved in the mechanism of the stimulation of mucus secretion and/or mucus accumulation in rat gastric mucosa and not directly concerned with the action of gastrin-induced gastric acid secretion.
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PMID:Influence of L-365,260, a CCK-B/gastrin receptor antagonist, on tetragastrin-stimulated mucin metabolism in rat gastric mucosa. 1035 22

We have previously developed a rapid, simple endoscopic method for evaluating gastrin-stimulated maximal acid output (the endoscopic gastrin test, EGT). In EGT, gastric fluid newly secreted over 10 min after gastrin stimulation is collected under direct endoscopic visualization. In this study, employing the EGT, we evaluated the effect of rebamipide, a cytoprotective anti-ulcer drug, on gastric mucus secretion. In ten Helicobacter pylori-negative healthy volunteers, gastric juice was collected by EGT prior to and after 4-week administration of rebamipide. The collected gastric juice was subjected to analysis for gastric mucus output. Total gastric mucin output was significantly increased by 53% by rebamipide administration from 3.2 +/- 1.2 mg hexose/10 min to 4.9 +/- 2.2 mg hexose/10 min (P < 0.01). Further analysis by ion-exchange chromatography revealed that rebamipide administration induced a specific increase in acidic mucin rich in sialic acid. Applying EGT, this study demonstrated that rebamipide administration increased gastric mucus secretion in human.
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PMID:Rebamipide, a cytoprotective drug, increases gastric mucus secretion in human: evaluations with endoscopic gastrin test. 1897 81


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