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)

The gastric effects of synthetic secretin given in a depot preparation as subcutaneous injection or in different doses as intravenous infusion were studied in 10 healthy volunteers. Peptone-stimulated gastric acid secretion and serum gastrin were significantly suppressed with a clear dose-response inhibition of acid output. There was a significant correlation between percentage inhibition of acid secretion and plasma secretin concentrations which were greatly above those seen physiologically. Serum lipase and trypsin increased significantly. Most subjects lost fluid from diuresis and diarrhoea, so that serum sodium and total protein concentrations also increased significantly. These side effects cast doubt on the clinical value of prolonged infusions of pharmacological doses of synthetic secretion in critically ill patients.
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PMID:Gastric effects and side effects of synthetic secretin in man. 728 Feb 90

The new CCK-B/gastrin receptor antagonist PD 136450 is of potential value in treating neurologic and psychiatric disorders. We investigated possible side effects on the rat pancreas using acute and chronic administration schedules. In chronic experiments, four groups of rats were given either PD 136450, the proton pump inhibitor BY 308 (in order to induce hypergastrinemia), a combination of both, or control solutions over 14 d. Pancreatic growth, DNA, and protein content were significantly increased in rats given PD 136450 irrespective of circulating gastrin levels. Furthermore, an anticoordinate shift in pancreatic enzyme content in favor of trypsin and chymotrypsin at the expense of amylase and lipase was observed. Plasma CCK levels remained unchanged in this group making a role of circulating hormone unlikely. In order to investigate a possible direct agonist effect of the CCK-B/gastrin receptor antagonist, we studied amylase release from isolated rat pancreatic acini in response to PD 136450 and sulfated CCK8 alone and in combination with the specific CCK-A receptor antagonist MK 329. Increasing concentrations of PD 136450 caused a monophasic dose-response curve in contrast to the well-known biphasic amylase release in response to CCK8. Addition of increasing doses of PD 136450 to a concentration of CCK causing maximal stimulation of amylase release (0.1 nM) further enhanced amylase release from pancreatic acini. The specific CCK-A receptor antagonist MK 329 dose-dependently inhibited CCK8- and PD 136450-induced amylase release. In conclusion, the new CCK-B/gastrin receptor antagonist PD 136450 exhibited profound agonist actions on the rat pancreas mediated via CCK-A receptors.
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PMID:A new CCK-B/gastrin receptor antagonist acts as an agonist on the rat pancreas. 752 49

While pancreatic metaplasia has been observed in gastric mucosa of patients with chronic gastritis, it has not been described in ectopic gastric mucosa. We have identified focal clusters of cells resembling pancreatic acinar cells (CPACs) in 11 of 350 biopsies of Barrett's mucosa from 120 patients with Barrett's esophagus enrolled in a clinical efficacy trial of omeprazole versus ranitidine for treatment of gastroesophageal reflux disease. Three additional cases from our surgical files were also studied. Immunoreactivity for trypsin and chymotrypsin was present in the CPACs of all 14 cases, while stains for alpha-amylase and lipase were each positive in 12 of 13. A few cells in the CPACs were also positive for chomogranins (12 of 13 cases), serotonin (seven of 13 cases), somatostatin (three of 12), gastrin (four of 11), and pancreatic polypeptide (two of 13). No staining was seen for insulin or glucagon. Ultrastructural studies performed in one case showed features of pancreatic exocrine and endocrine (PP-type) cells in cells within CPACs. These results collectively indicate that the CPACs are aggregates of true pancreatic acinar cells admixed with a few endocrine cells. This pancreatic parenchyma in Barrett's mucosa is most likely of metaplastic origin and could be derived from the transitional zone cells or from pluripotent stem cells in the esophageal mucosa or from metaplasia of mucus cells. While the development of pancreatic metaplasia in Barrett's esophagus appears to be unrelated to drug therapy, the clinical relevance of this distinctive histological finding needs further investigation.
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PMID:Pancreatic metaplasia in Barrett's esophagus. An immunohistochemical study. 757 75

In the cat, gastric lipase secretion was equally but weakly stimulated by pentagastrin, a major stimulant of acid secretion, and by carbamylcholine, a major stimulant of pepsin secretion. Lipase was also stimulated by fresh liver, which induces a large blood gastrin release and not by canned food, which is a poor gastrin releaser. Lipase output always preceded that of acid an pepsin. Lipase was not correlated with acid and pepsin secretion while acid and pepsin were well correlated during all stimulations but not in basal state. Lipase is co-localized with pepsin in the chief cells but is also present in pepsin-free cells, the mucus surface cells of the fundus and the antrum. The distribution of lipase explains the lack of correlation between pepsin and lipase as already mentioned. However, our data show that lipase secretion is under the control of gastric stimulants and might play a role in the gastric initiation of pancreatic meal lipolysis.
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PMID:Variation of gastric lipase secretion in the Heidenhain pouch of the cat. 768 84

Somatostatin is a 14 amino acid peptide that inhibits pancreatic exocrine and endocrine secretion. Its clinical application has been limited by its very short half life, necessitating continuous intravenous infusion. Octreotide is an 8 amino acid synthetic analogue of somatostatin that possesses similar pharmacological effects. It has a much longer duration of action, however, and can be given subcutaneously. Both the intravenous and subcutaneous routes of injection of octreotide are well tolerated. Peak serum concentrations occur within 30 minutes after subcutaneous administration and within four minutes of a three minute intravenous infusion. Serum concentration increases linearly with dose. Octreotide is distributed rapidly, mainly in the plasma, where it is 65% protein bound. The elimination half life is about 1.5 hours and about 32% of a subcutaneous dose is excreted in the urine as unchanged octreotide. Octreotide inhibits gastroenteropancreatic secretion, especially of insulin, glucagon, pancreatic polypeptide, gastric inhibitory polypeptide, and gastrin. It also inhibits both release of thyroid stimulating hormone and growth hormone secretion in response to exercise, insulin induced hypoglycaemia, and argenine stimulation. Octreotide reduces splanchnic blood flow in healthy volunteers and hepatic venous pressure in cirrhotic patients. It can accelerate or delay gastric emptying, prolong transit time at moderate to high doses, stimulate motility at low doses, and inhibit gall bladder emptying. Octreotide considerably inhibits pentagastrin stimulated gastric acid secretion and significantly diminishes exocrine pancreatic function (amylase, trypsin, lipase). Octreotide increases intestinal transit time and decreases endogenous fluid secretion in the jejunum and ileum, thus increasing the absorption of water and electrolytes. These pharmacological effects of the analogue point to its therapeutic role in a variety of endocrine and gastrointestinal disorders.
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PMID:Somatostatin and somatostatin analogues: pharmacokinetics and pharmacodynamic effects. 791 41

The kinetics of the gastric secretion of lipase, pepsin and acid were studied after a meal in Heidenhain-pouch rabbits. After a 24-h fast, feeding immediately stimulated (< 15 min) lipase (x 4.1) and later on pepsin (x 1.8) output which reached respectively 16 and 47% of the output observed after pentagastrin stimulation (64 micrograms.kg-1.h-1 for 1 h), and which were significantly correlated. Lipase concentration was enhanced earlier and to a greater degree (x 7.3) than pepsin concentration (x 2.5). No stimulation of high basal acid secretion occurred. It was concluded that: 1) gastric lipase secretion is stimulated by feeding in the rabbit; 2) pepsin secretion is stimulated by feeding. The modalities of the secretion of lipase and pepsin are compatible with the existence of distinct secretory cells; 3) acid secretion is not stimulated by feeding. The decrease in acid secretion during the post-prandial phase favors a physiological role for lipase which is altered by low pH. The absence of acid stimulation by feeding in the rabbit, in contrast to other species, requires additional studies on the release of gastrointestinal hormones, namely gastrin, cholecystokinin and somatostatin.
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PMID:Post-prandial lipase, pepsin and acid secretion of a Heidenhain pouch in the rabbit. 821 48

We have investigated the role of intestinal fat digestion in fat-induced suppression of gastric acid secretion and gastrin release in the rat. Intraduodenal administration of oleic acid (10%, pH 6.5) and triglyceride (10%, pH 6.5) at a rate of 2 ml/hr resulted in significant suppression of gastric acid secretion and gastrin release stimulated by intragastric perfusion of peptone (0.5%). Diversion of pancreatic juice from the duodenum completely abolished triglyceride-induced inhibition of peptone-stimulated gastric acid secretion and plasma gastrin release, but oleic acid-suppressed gastric acid secretion and gastrin release were unaffected by pancreatic juice diversion. Intraduodenal administration of digested triglyceride, prepared by preincubation with lipase, caused significant suppression of the peptone-induced gastric acid secretion and rise in plasma gastrin levels, even though pancreatic juice was excluded. The results of this study indicate that digestive products of triglyceride by pancreatic juice, especially by lipase, are responsible for the intestinal fat-induced inhibition of gastric acid secretion and gastrin release and that intestinal fat digestion plays a significant role in the mechanism.
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PMID:Intestinal fat digestion plays a significant role in fat-induced suppression of gastric acid secretion and gastrin release in the rat. 826 32

We studied the effect of intravenous infusion of synthetic truncated GLP-1 (proglucagon 78-107-amide) on fasting and postprandial gastric acid secretion, gastric emptying, and pancreatic secretion of trypsin and lipase in eight normal volunteers using marker dilution and aspiration technique. The infusion resulted in a plasma concentration of 110 +/- 14 pmol/liter (mean +/- SEM). Truncated GLP-1 significantly inhibited postprandial acid secretion by 43 +/- 11% in spite of unchanged plasma gastrin concentration. Gastric emptying rate decreased significantly; 50% emptying time increased from 16 +/- 2 min to 30 +/- 5 min. Postprandial trypsin and lipase outputs were significantly inhibited by 47 +/- 17% and 40 +/- 9% during truncated GLP-1 infusion. Pancreatic enzyme output was linearly correlated to gastric emptying, and truncated GLP-1 did not affect this relationship, suggesting that the effect on pancreatic secretion was secondary to the effect on gastric emptying. Postprandial insulin and glucagon concentrations were similar with and without truncated GLP-1 infusion in spite of significantly lower blood glucose levels (5.2 +/- 0.2 versus 3.7 +/- 0.3), indicating that GLP-1 stimulated insulin secretion and inhibited glucagon secretion. In conclusion, our results suggest that truncated GLP-1 act as a physiological inhibitor of gastric and pancreatic functions in man.
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PMID:Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. 846 65

Little is known about the role of the gastric phase in the postprandial pancreaticobiliary response. We evaluated the effect of antral distension on pancreatic, biliary, and gastric secretions and on the release of cholecystokinin (CCK), gastrin, and pancreatic polypeptide in five healthy volunteers. Studies were performed using a duodenal tube with an inflatable balloon in the antrum and a separate gastric tube. Outputs were compared with responses to a maximal CCK stimulus (caerulein), and the role of cholinergic mechanisms was investigated using atropine. Graded antral distension by 50-, 200-, and 350-ml balloon volumes and constant antral distension by 350 ml elicited a marked stimulation of pancreaticobiliary secretions. Mean lipase outputs amounted to 52-60%, and mean bilirubin outputs reached 14-22% of maximal. Atropine completely abolished pancreaticobiliary responses to antral distension. Antral distension did not affect bicarbonate and gastric secretions. Plasma pancreatic polypeptide levels increased markedly during antral distension, and this effect was completely suppressed by atropine. There were no changes in circulating gastrin and CCK. These data demonstrate that antral distension with already small volumes of 50 ml elicits a hitherto unknown potent stimulatory effect, indicating a major role of the antrum in the postprandial pancreaticobiliary response in humans, which is mediated by cholinergic mechanisms.
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PMID:Role of antrum in regulation of pancreaticobiliary secretion in humans. 896 97

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


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