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 effects of metiamide, a histamine H2-receptor antagonist, and propranolol, a beta-adrenergic blocking agent, on gastric secretion were studied in anesthetized dogs. Metiamide, 1.45 mg/kg i.v., markedly inhibited the gastric secretion induced by a continuous i.v. infusion of tetragastrin (8 microng/kg-hr), histamine dihydrochloride (160 microng/kg-hr), or methacholine bromide (100 microng/kg-hr). Propranolol 0.5 or 1.0 mg/kg i.v. produced a significant potentiation of tetragastrin-induced gastric secretion but no influence of the secretion induced by methacholine. Propranolol at 5 or 10 mg/kg i.v. produced a slight reduction of the tetragastrin-induced secretion and a significant reduction of methacholine-induced secretion. Histamine-induced gastric secretion was not affected by propranolol at either 1 and 10 mg/kg i.v. These findings lend support to the hypothesis that interactions among histamine, gastrin and acetylcholine receptors do occur though the degree would not be the same in all directions.
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PMID:Effects of metiamide and propranolol on gastric secretion in anesthetized dogs. 1 25

Cimetidine, a non-thiourea-containing H2-receptor antagonist, was studied in seven patients with duodenal ulcer. Oral doses of 100, 200, and 300 mg were tested. Each dose significantly inhibited basal and meal-stimulated secretion. After 300 mg, basal acid secretion was essentially zero for at least five hours. The meal-stimulated three-hour acid output after the 300-mg dose was reduced by 67%. Cimetidine, 300 mg, decreased meal-stimulated acid secretion significantly more than an optimal effective dose of propantheline bromide (P less than 0.05). Inhibition of meal-stimualted gastric acid secretion showed a significant relation to peak blood cimetidine concentration (r is equal to 0.76, P less than 0.01). Cimetidine did not affect meal-stimulated gastrin release. No toxicity was observed after serial doses given during these tests. Cimetidine may be useful in treatment of acid-peptic diseases provided no important toxicity appears on chronic testing.
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PMID:Inhibition of gastric acid secretion by cimetidine in patients with duodenal ulcer. 23 46

Plasma gastrin concentrations and gastric acid output after modified sham feeding were determined in 20 duodenal ulcer patients. Sham feeding produced an acid response corresponding to 40-68% of the maximal acid output after pentagastrin stimulation, with no significant increase of plasma gastrin concentrations. In eight patients proximal gastric vagotomy almost abolished the acid responses to both insulin hypoglycaemia and sham feeding. Sham feeding in the vagotomised patients did not change the gastrin concentrations in plasma. After pretreatment with benzilonium, an anticholinergic with minimal central nervous effects, plasma gastrin concentrations increased after sham feeding. The study confirms that sham feeding is a poor stimulus for gastrin release in duodenal ulcer patients and supports a cholinergic inhibition of gastrin release. Intravenous injection of benzilonium bromide in a dose close to 70 micrograms/kg, and atropine in the low dose of 30 micrograms/kg inhibited the acid response to sham feeding by about 65%. Atropine in a dose of 50 micrograms/kg virtually abolished the acid sham feeding response, possibly owing to ganglionic or central nervous blockade. Vagal activation of the acid secretory glands does not seem to involve a purely cholinergic neurotransmission.
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PMID:Effect of proximal gastric vagotomy and anticholinergics on the acid and gastrin responses to sham feeding in duodenal ulcer patients. 39 71

The purpose of the present series of tests was to measure and compare the effects of ingestion of gelatin capsules containing 15(R)-15-methyl PGE2 (PG) and/or an anticholinergic drug (methscopolamine bromide, Pamine) on meal-induced gastric acid secretion and serum gastrin level. Eleven duodenal ulcer patients were stimulated by a 5% peptone meal. Acid secretion was determined by the intragastric titration technique, and serum gastrin was measured by radioimmunoassay. The tests were randomized and double-blind. PG alone given 30 min before a test meal at a dose of 50 micrograms or 100 micrograms produced no side effects and inhibited meal-stimulated acid secretion by about 43% and 55%, respectively. Gastric acid inhibition after a single dose of PG was most pronounced in the first hour of a test meal and was accompanied by almost complete suppression of the meal-induced serum gastrin level. Pamine alone in a dose of 2.5 mg reduced gastric acid response to a meal by about 29% but caused a further rise of postprandial serum gastrin level over control values. The combination of PG, 50 micrograms, and Pamine, 2.5 mg, did not result in significantly greater acid inhibition (about 48%) than when either compound was given alone. When the higher dose of PG (100 micrograms) was given together with Pamine (2.5 mg), the degree of inhibition produced by PG alone was not changed. It is concluded that PG given orally in capsules is a potent inhibitor of gastric acid and serum gastrin response to a meal and that this effect may be of potential value in the treatment of peptic ulcer disease.
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PMID:Effect of orally administered 15(R)-15-methyl prostaglandin E2 and/or an anticholinergic drug on meal-induced gastric acid secretion and serum gastrin level in patients with duodenal ulcers. 39 27

This study compared the actions and interactions of human synthetic gastrin, octapeptide-cholecystokinin (OP-CCK), cholecystokinin (CCK), and secretin on the amplitude of isometric tension developed in strips of dog antral smooth muscle in vitro. Cholecystokinin, OP-CCK, and gastrin produced maximal stimulatory effects at 7.5 x 10(-9), 4.5 x 10(-9), and 3.5 x 10(-9) M, respectively. Secretin alone was ineffective up to 2.5 x 10(-8) M. Observed maximal responses to gastrin, OP-CCK, and CCK tested alone were not significantly different. A submaximal gastrin dose added with OP-CCK, shifted the OP-CCK dose-response curve to the left and significantly reduced the D50, but the calculated maximal response (CMR) did not change. Also, submaximal OP-CCK plus gastrin shifted the gastrin dose-response curve to the left and significantly lowered the D50 with no change in CMR. Secretin decreased CMR but did not change the D50 for gastrin. Responses obtained to gastrin and OP-CCK tested alone were not affected by tetrodotoxin (1 x 10(-5) M), hexamethonium bromide (4 x 10(-5) M), or atropine (1 x 10(-7) M). Larger doses of atropine (5 x 10(-6) M) reduced peptide responses an average 30%. The results indicate that OP-CCK, CCK, and gastrin share a common noncholinergic receptor site. Secretin acts at a different receptor site.
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PMID:Interaction between gastrin, CCK, and secretin on canine antral smooth muscle in vitro. 43 48

Pharmacokinetics and gastric secretion suppressing properties of a new drug, trithiozine (TR), were studied in man. Its availability, if taken orally, is prompt and very good; its blood plasma level lasts for over 5 hr. In basal conditions volume of gastric juice is suppressed by TR as it is by propantheline bromide (PPB). In contradistinction to PPB, TR reduces basal acid output. After histamine stimulation TR is not as effective as PPB in reducing both volume and acid output. TR did not appear to affect the plasma gastrin level. Lack of typical anticholinergic side-effects such as dryness in mouth, vision blurring, etc., on the one hand, and antisecretory activity limited to basal conditions on the other, seem to offer a new modification of the old approach to therapy of gastroduodenal ulcer. Clinical trials seem justified.
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PMID:Bioavailability of trithiozine (TR) in man and its relation to gastric secretion and gastrin plasma level. 76 54

The effect of intragastric and intraduodenal 16,16-dimethyl prostaglandin E2 (dm PGE2) on meal-stimulated gastric acid secretion and gastrin release was studied in patients with inactive duodenal ulcer. Compared to placebo, doses of 0.75, 1.00, 1.33, and 1.77 mug per kg of dm PGE2 instilled into the stomach inhibited meal-stimulated gastric acid secretion by 61 to 94% (P less than 0.01). The 1.00, 1.33, and 1.77 mug per kg doses inhibited acid secretion significantly (P less than 0.05) more than an optimal dose of propantheline bromide. Intragastric dm PGE2 (1 mug per kg) was significantly (P less than 0.05) more effective than intraduodenal dm PGE2 (1 mug per kg) in inhibiting both gastric acid secretion and gastrin release. After 1.33 and 1.77 mug per kg, some patients experienced abdominal cramps, or diarrhea, or both, but at doses of 1.00 mug per kg or less no apparent untoward side effects were observed. It is concluded that 16,16-dm PGE2 significantly inhibits meal-stimulated gastric acid secretion and gastrin release, and may be of therapeutic value in patients with peptic ulcer provided it is free of untoward side-effects with chronic administration.
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PMID:The effect of 16,16-dimethyl prostaglandin E2 on meal-stimulated gastric acid secretion and serum gastrin in duodenal ulcer patients. 125 35

The influence of cholinergic blockade as well as vagal denervation of the oxyntic gland mucosa on the gastrin response to gastrin-releasing peptide (GRP) have been studied in patients with duodenal ulcer disease. The gastric luminal content was neutralized during the experiments. GRP induced a substantial increase in gastrin levels with a peak response already after 15 min of infusion. Vagal denervation of the parietal cell area induced a significant increase in basal gastrin concentrations and a significant enhancement of the GRP response. Two different doses of benzilonium bromide were studied and neither influenced the basal concentrations of gastrin. A significantly increased gastrin response to GRP was, however, observed after administration of both a high and a very low dose of the anticholinergic drug. Our results delineate a vagal, noncholinergic inhibitory influence on the basal gastrin release. In addition a vagally dependent oxyntopyloric mechanism inhibits the gastrin release stimulated by GRP. This inhibitory mechanism may hypothetically be a cholinergic reflex mechanism.
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PMID:Effect of parietal cell vagotomy and cholinergic blockade on gastrin release in man induced by gastrin-releasing peptide. 225 22

The peptide gastrin has been shown to have growth stimulatory effects on normal as well as malignant gastrointestinal tissue. In this study, we have examined the possibility of autocrine growth-stimulation of cultured colon tumor cells by a gastrin-like peptide. The gastrin/CCK receptor antagonist dibutyryl cGMP inhibited the proliferation of two human colon carcinoma cell lines HCT 116 (EC50 = 1.3 mM) and CBS (EC50 = 2.5 mM) in a dose-dependent manner. Marked morphological changes were observed in HCT 116 cells after treatment with 1 mM dibutyryl cGMP. In receptor binding assays, dibutyryl cGMP competed with 125I-labeled gastrin for binding to HCT 116 cells (IC50 = 1.8 mM). Another derivative of cyclic GMP, 8-Bromo cGMP used as control due to its considerably weaker affinity for the gastrin/CCK receptor, did not compete with radiolabeled gastrin for binding to HCT 116 cells and had no effect on the morphology or proliferation in monolayer cultures of HCT 116 or CBS cells at concentrations up to 10 mM. Antigastrin/CCK antisera was also found to have dose-dependent cytostatic effects on HCT 116 and CBS cells adapted to growth in serum-free medium. The antiproliferative effect of the gastrin/CCK receptor antagonist and antigastrin/CCK antibodies suggested that a gastrin-like peptide secreted by these cells may promote growth. Radioimmunoassay of the conditioned medium of these two cell lines indicated the presence of a gastrin-like peptide (10-50 pg/10(6) cells/72 h). Northern analysis using an oligonucleotide DNA probe complementary to the nucleotide sequence coding the dodecapeptide carboxyl terminal of human gastrin showed three transcripts (0.7, 3.3, and 3.7 kb) that hybridized with the probe. These data provide, for the first time, evidence for an autocrine growth stimulatory role of a gastrin/CCK-like peptide in cultured colon tumor cells.
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PMID:Evidence for autocrine growth stimulation of cultured colon tumor cells by a gastrin/cholecystokinin-like peptide. 229 33

The effect of electrical stimulation of the vagus nerves on the release of immunoreactive gastrin-releasing peptide (GRP), gastrin, and somatostatin was investigated using the isolated perfused rat stomach. Electrical stimulation (10 Hz, 1 ms duration, 10 V) of the peripheral end of the subdiaphragmatic vagal trunks produced a significant increase in both GRP and gastrin but a decrease in somatostatin. The infusion of atropine sulfate at a concentration of 10(-5) M augmented GRP release and reversed the decrease in somatostatin release in response to vagal stimulation to an increase above basal levels. However, the gastrin response to vagal stimulation was not affected by atropine. The infusion of hexamethonium bromide at a concentration of 10(-4) M significantly suppressed GRP release but did not affect gastrin secretion in response to vagal stimulation. On the other hand, the somatostatin response to vagal stimulation was completely abolished by hexamethonium. These findings lead us to conclude that the intramural GRP neurons might play an important role in the regulation of gastrin as well as somatostatin secretion and that somatostatin secretion may be controlled not only by a cholinergic inhibitory neuron but also by a noncholinergic, e.g., peptidergic stimulatory neuron, both of which may be regulated through preganglionic vagal fibers via nicotinic receptors. In addition, because the infusion of 10(-7) M GRP suppressed the somatostatin secretion, we suggest that either GRP should be excluded from the list of candidates for the noncholinergic stimulatory neurotransmitter for somatostatin secretion or that there are different mechanisms of action for endogenous and exogenous GRP.
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PMID:Vagal regulation of GRP, gastric somatostatin, and gastrin secretion in vitro. 285 78


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