Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the relative contributions of neural reflexes and intestinal hormones to the inhibition of gastric acid secretion by intestinal acidification, rats with an extrinsically denervated, transplanted segment of jejunum, and those with an innervated segment of jejunum, were studied. Postoperatively, meal-stimulated gastric acid secretion was measured. When the acid secretory response to intragastric liver extract reached a plateau, graded concentrations of hydrochloric acid or saline were instilled into the jejunal segments. Gastric acid secretion was inhibited by intrajejunal acid (pH 2.5) by 79% in the innervated rats and by 64% in the transplanted group. Thus at a pH of 2.5 there was a 15% greater maximum inhibition of plateau acid response in the innervated rats than in the transplanted rats, presumably because of the extrinsic neural contribution. To examine the hormonal mediators, the effects of a somatostatin monoclonal antibody and a CCK-A receptor antagonist (L 364718) on acid-induced inhibition of gastric acid secretion were studied in transplanted rats. Treatment with a somatostatin monoclonal antibody or with L 364718 reduced the acid-induced (pH 2.5) inhibition of gastric acid secretion by 93 and 27%, respectively. Jejunal acidification inhibits gastric acid secretion in the rat by both neural and hormonal mechanisms. The hormonal mechanism is mediated by somatostatin and CCK.
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PMID:Intestinal acid inhibits gastric acid secretion by neural and hormonal mechanisms in rats. 134 53

Intracerebroventricular administration of SMS 201-995 (5 micrograms/rat), a somatostatin analogue, induced barrel rotation in rats. Pretreatment with ceruletide (40 micrograms/100 g b. wt., IP) 3 days or 7 days prior to the injection of SMS 201-995 significantly inhibited the response rate of barrel rotation induced by SMS 201-995, but not that induced by arginine-vasopressin (1 microgram/rat, ICV). The suppressive effect of ceruletide on barrel rotation could be partially countered by MK-329, a selective peripheral CCK (CCK-A) receptor antagonist. Desulfated cerulein did not affect the barrel rotation induced by SMS 201-995. These findings suggest that ceruletide specifically suppresses the barrel rotation evoked by SMS 201-995 in a long-lasting manner possibly acting through CCK-A receptor.
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PMID:Barrel rotation in rats induced by SMS 201-995: suppression by ceruletide. 208 92

Helicobacter pylori infection may be associated with duodenal ulcer (DU) and accompanied by enhanced gastrin release but the mechanism of this H pylori related hypergastrinaemia in DU patients is unclear. Cholecystokinin (CCK) has been implicated in the feedback control of gastrin release and gastric acid secretion in healthy subjects. This study therefore investigated if CCK participates in the impairment of postprandial gastrin release and gastric secretion in six DU patients. Tests were undertaken with and without elimination of endogenous CCK by loxiglumide, a selective CCK-A receptors antagonist, before and after eradication of H pylori with triple therapy (omeprazole, amoxicyllin, bismuth). In H pylori positive DU patients, the post-prandial decline in pH (with median pH 3.5) was accompanied by a pronounced increment in plasma gastrin but the administration of loxiglumide did not affect significantly this postprandial rise in plasma gastrin and gastric pH profile. After eradication of H pylori, the plasma gastrin concentration was reduced while the median postprandial pH was significantly increased (median pH 4.3). The administration of loxiglumide resulted in significantly greater increase in postprandial plasma gastrin and greater decrease in pH (median pH 3.1) in these patients. This study shows that (a) infection with H pylori is accompanied by an enhanced gastrin release and gastric acidity in DU patients, (b) the failure of loxiglumide to affect plasma gastrin or gastric acid secretion in H pylori infected DU patients could be attributed, at least in part, to the failure of endogenous CCK to control gastrin release and gastric secretion by releasing somatostatin, and (c) the test with loxiglumide may be useful in the identification of patients with impaired feedback control of gastrin release and gastric secretion resulting from infection with H pylori.
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PMID:Eradication of Helicobacter pylori restores the inhibitory effect of cholecystokinin on postprandial gastrin release in duodenal ulcer patients. 748 32

Cholecystokinin (CCK) is the major hormonal stimulus of gallbladder contraction. Both somatostatin and CCK-A receptor antagonists inhibit stimulation of the gallbladder by CCK. The aim of this study was to compare the effect of somatostatin and the CCK-A receptor antagonist loxiglumide (CR 1505) on gallbladder volume at baseline and after feeding. In random order nine healthy subjects received somatostatin (IV loading dose 125 micrograms, followed by IV infusion of 125 micrograms.h-1), loxiglumide (10 mg.kg-1.h-1) and control saline. Gallbladder volumes and plasma CCK levels were measured basally and during stimulation by an intraduodenal infusion of fat using, respectively, ultrasound and a sensitive and specific radioimmunoassay. Mean basal gallbladder volume was similar prior to the saline control (28.5 ml), loxiglumide (28.7 ml) and somatostatin (23.4 ml) experiments. In the control experiment, intraduodenal fat led to a significant increase in plasma CCK from 2.6 to 4.8 pmol.1-1, accompanied by contraction of the gallbladder to 2.0 ml. Loxiglumide induced dilatation of the gallbladder to 40 ml and prevented the any contraction in response to intraduodenal fat. During the somatostatin infusion, gallbladder volume remained the same both basally and during fat stimulation. The plasma CCK response to intraduodenal fat was exaggerated by loxiglumide and was abolished by somatostatin.
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PMID:Effects of somatostatin and loxiglumide on gallbladder motility. 776 49

Cholecystokinin stimulates pancreatic zymogen secretion by binding with high affinity to a receptor on the pancreatic acinar cell. This receptor has been cloned and shown to be a CCK-A subtype. CCK also stimulates pepsinogen secretion from the gastric chief cell with high affinity. Using polymerase chain reaction with primers from the known sequence of the rat pancreatic CCK-A receptor cDNA, we prepared a 600 bp product from rat and rabbit stomach cDNA. From Southern analysis these represented a fragment of a gastric CCK-A receptor. PCR was then used to amplify a rabbit lambda ZAP II gastric epithelial cDNA library with the same primers, and the product was identified by sequencing as representing a CCK-A receptor fragment. When this PCR product was used to screen the library, ten positive clones were identified in a screening of 4.10(5) plaques, and several of these were sequenced. All had essentially the same sequence contained within 2 of these clones consisted of 427 amino acids and was 92% homologous (87% identity) to the known rat pancreatic CCK-A sequence but only 43% homologous to the gastric CCK-B sequence. The cDNA was subcloned into a pcDNA1 expression vector and transiently expressed in the human embryonic kidney cell line, HK 293. The responses of intracellular Ca2+ in these transfected cells to CCK and gastrin were monitored using video imaging. On the average 40% of the cells responded to CCK-8 by a transient elevation of [Ca2+]i followed by a steady state plateau. CCK was a high and gastrin a low affinity ligand for this signal, corresponding to the actions of these ligands on pepsinogen secretion from chief cells and somatostatin release from D cells. Hence from sequence and second messenger responses, the clone represents the CCK-A receptor presumably responsible for pepsinogen secretion by gastric chief cells and somatostatin release from gastric D cells.
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PMID:Cloning and expression of the rabbit gastric CCK-A receptor. 791 28

CCK8 is a poor stimulant of gastric acid secretion in vivo, but is equipotent to gastrin-17 (G17) in in vitro systems. To further evaluate the role of cholecystokinin (CCK) in regulating acid output in humans, dose-response curves were constructed to CCK8 or G17 (6.4-800 pmol kg-1 per h) with and without a specific CCK-A receptor antagonist (loxiglumide). During loxiglumide infusion, G17-stimulated acid output was unchanged, whereas CCK8-stimulated secretion increased significantly. Gastric somatostatin-14 release increased fivefold with CCK8 alone, but was blocked with loxiglumide administration. These data suggest that CCK8 directly stimulates acid secretion by binding to a CCK-B/gastrin receptor on parietal cells, but at the same time inhibits acid responses by stimulating gastric somatostatin release to a CCK-A receptor-mediated pathway. To test which action of CCK is relevant under physiological circumstances, the effect of loxiglumide on fasting and post-prandial acidity was measured through continuous pH-metry. After eating, gastrin levels increased fourfold compared to controls with concomitant increases in acid secretion. These results suggest that post cibum, CCK is an inhibitor of acid secretion by regulating gastrin through local somatostatin; they support the hypothesis that CCK acts as an enterogastrone.
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PMID:Cholecystokinin is a physiological regulator of gastric acid secretion in man. 795 87

Despite the extensive amino acid homology between gastrin and cholecystokinin (CCK) at the biologically active carboxyl terminus, the receptors through which these peptides exert their action are heterogeneous. In previous studies, we have examined the biological activity of gastrin/CCK peptides on isolated canine fundic D-cells and observed that CCK is a more potent and efficacious stimulant of somatostatin release than gastrin. We performed the present studies to distinguish between distinct CCK (CCK-A subtype) and gastrin (CCK-B/gastrin subtype) receptors on canine D-cells. Consistent with this observation was our finding that the CCK-A receptor selective antagonist L-364,718 dose dependently (10(-11)-10(-7) M) inhibited CCK-mediated somatostatin release but at the same doses did not alter the effect of gastrin. CCK and gastrin exhibited similar potency in displacing bound 125I-labeled Leu15 gastrin-17 from D-cells. However, when 125I-CCK octapeptide (CCK-8) was used as the radioligand, a fraction of the bound label could not be displaced with gastrin, but this fraction was completely displaced with CCK-8. In D-cells pretreated with high concentrations of gastrin, L-364,718 was able to inhibit the gastrin-resistant fraction of 125I-CCK-8 binding, but the CCK-B/gastrin receptor selective antagonist (PD 134308) was unable to influence this fraction of binding in doses as high as 10(-6) M. These studies delineate the presence of distinct CCK-A and CCK-B/gastrin receptors on canine fundic D-cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distinct receptors for cholecystokinin and gastrin on canine fundic D-cells. 809 10

In this study, a selective antagonist of cholecystokinin (CCK)-A receptors, loxiglumide, was used to evaluate the role of CCK in the control of the release of gastrin and pancreatic hormones (insulin, glucagon, pancreatic polypeptide (PP), and somatostatin) after stimulation with exogenous CCK and ingestion of a standard liquid mixed meal in healthy humans. Exogenous CCK-8, which induced a small but significant increase in gastric acid secretion, resulted in dose-dependent increments in plasma PP levels without significant changes in plasma levels of insulin, glucagon, or somatostatin. Pretreatment with loxiglumide resulted in a marked increase in CCK-induced gastric acid secretion and abolished the increments in plasma PP without alteration of plasma insulin, glucagon, or somatostatin levels. Ingestion of the liquid meal resulted in an immediate rise in intragastric pH from basal values of about 2 to pH6 lasting 90-120 min, and this was accompanied by significant increments in plasma gastrin, insulin, glucagon, PP, and somatostatin. Administration of loxiglumide (1200 mg orally) caused a reduction in the postprandial intragastric pH and the two- to three-fold increase in plasma gastrin. Plasma insulin and glucagon levels in tests with loxiglumide tended to increase, probably owing to accelerated gastric emptying, whereas plasma PP and somatostatin were significantly reduced. This study provides evidence that CCK exerts an inhibitory effect on gastric acid secretion and plasma gastrin release as well as a stimulatory influence on the release of PP and somatostatin via CCK-A receptors but does not influence directly insulin or glucagon secretion in man.
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PMID:Cholecystokinin in the regulation of gastric acid and endocrine pancreatic secretion in humans. 851

Activation of type A receptors by CCK or cerulein is known to stimulate pancreatic enzyme secretion, but its role in the amino acid (AA) consumption and enzyme synthesis remains unclear. In our study, we used loxiglumide, a potent CCK-A-receptor antagonist, to investigate the role of CCK-A receptors in pancreatic consumption of circulating AAs and enzyme secretion. Five healthy male volunteers were intubated with double-lumen duodenal tube, and duodenal aspirates were collected during 60-min basal periods and then during pancreatic stimulation with iv infusion of secretion (80 pmol/kg/h) plus cerulein (50 pmol/kg/h) during three consecutive 30-min periods. The same procedure was repeated, but secretin-cerulein infusion was combined with a constant dose of loxiglumide (20 mumol/kg/h). The volume and outputs of HCO3-, protein and enzymes (amylase and trypsin) in duodenal aspirates and gallbladder volume (by sonography) were determined at 30-min intervals. Plasma samples were drawn for total plasma AA assay by ninhydrin method to assess the pancreatic uptake of free AAs. Infusion of secretin plus cerulein caused a several-fold increase in the volume of duodenal aspirate and the outputs of HCO3-, protein, and enzymes. During those periods, plasma AA level decreased from initially 2.20 +/- 0.3 mmol/L to 1.09 +/- 0.3 mmol/L (p < 0.01) and the gallbladder volume from initially 28 +/- 8 mL to 2 +/- 0.4 mL. This increase in pancreatic secretory outputs was accompanied by significant increments in plasma insulin, glucagon, PP, and somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cholecystokinin (CCK) in the amino acid uptake and enzyme protein secretion by the pancreas in humans. 856 35

Helicobacter pylori (Hp) infection may be associated with duodenal ulcer (DU) and accompanied by increased release of gastrin and deficiency of somatostatin (S-S) but the mechanisms of these changes in DU patients after eradication of Hp have been little studied. Cholecystokinin (CCK) has been implicated in the feedback control of gastric acid secretion in healthy subjects but its contribution to secretory disorders in DU patients has been little examined. This study, therefore, investigated whether CCK participates in the impairment of postprandial gastrin release and gastric acid secretion in active DU patients. Tests were undertaken in 10 DU patients without or with elimination of the action of endogenous CCK using loxiglumide (LOX), a selective CCK-A receptor antagonist, before and 4 wk. after eradication of Hp with triple therapy (omeprazole, amoxycillin and bismuth). In Hp positive DU patients, the postprandial acid secretion (measured by continuous intragastric pH monitoring) was accompanied by a pronounced increment in plasma gastrin with negligible increase of intraluminal release of S-S. The administration of LOX in these patients did not affect significantly the postprandial pH profile and the rise in plasma gastrin. After eradication of Hp the median postprandial intragastric pH increased to about 4.3 (compared to 3.5 before the Hp eradication); the postprandial gastrin concentration was reduced by about 40%, while luminal release of S-S was increased 2 folds. The administration of LOX resulted in significantly greater decrease in median pH (3.1) and higher rise in postprandial plasma gastrin in these patients. Also the postprandial plasma S-S showed a small, but significant decline (by about 25%) as compared to that in placebo treated patients. This study provides evidence that: (1) Hp infection in DU patients is accompanied by enhanced gastrin release and the reduction in luminal release of S-S; (2) The failure of LOX to affect gastric secretion and plasma gastrin DU Hp infected patients could be attributed, at least in part, to the failure of endogenous CCK to control gastric acid secretion via release of S-S; (3) Hp infected patients appear to exhibit a deficiency of S-S release that can be reversed by the eradication of Hp indicating that both peptides may contribute to the acceleration of the ulcer healing following Hp eradication in DU patients; (4) The test with LOX and gastric luminal S-S assay may be useful in identification of Hp positive DU patients with CCK-mediated impaired feedback control of gastric secretion and deficiency of S-S caused by Hp infection.
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PMID:Eradication of Helicobacter pylori and gastrin-somatostatin link in duodenal ulcer patients. 877 96


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