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)

1. Extracts of antral, duodenal and jejunal mucosa contained the same concentrations and molecular forms of gastrin in cat and dog. In both species component III constituted 93%, component II 4% and components I and IV each 1% of the total immunoreactivity. 2. During electrical vagal stimulation or feeding in (a) anaesthetized cats with ligated kidney vessels and resected jejunum and ileum, (b) anaesthetized normal cats or (c) conscious normal cats, release of the large molecular forms of gastrin, components I and II, was not detectable. 3. Luminal perfusates of cat antrum contained only component III and occasionally less than 2% of component IV. 4. Intravenous injections into conscious cats of components I, II and III isolated from cat antrum revealed a significantly slower elimination of the large components (t1/2 approximately 4.2 and 4.0 min respectively) than of component III (t1/2 approximately 1.1 min). Thus the absence of components I and II in cat blood cannot be due to rapid degradation. 5. During feeding, components I and II constituted 20% of the total gastrin immunoreactivity in antral venous blood of dogs. This amount is sufficient to account for the predominance of large components in peripheral venous blood in dogs considering their slow metabolic clearance rates. 6. Luminal perfusates of dog antrum contained components I, II and III in proportions corresponding to those found in antrum. 7. The results indicate that components I and II are synthesized in the same proportions in gastrin cells of cat and dog. In the cat, components I and II are, however, never released from the cells. Since these components contain heptadecapeptide gastrin within their sequeaces, they probably represent biosynthetic precursors of the principal gastrin, the heptadecapeptide (component III). The predominance of component III in gastric juice suggests that the feline gastrin cell secretes only component III, which degrades to component IV in blood.
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PMID:Gastrins in cat and dog: evidence for a biosynthetic relationship between the large molecular forms of gastrin and heptadecapeptide gastrin. 72 81

The effects of ethyl alcohol, 20%, were measured on steady state rates of ion transport by isolated mucosa. Luminal, but not serosal, addition of alcohol altered ion transport. Alcohol caused a sustained reduction in apparent basal acid secretion by fundic mucosa. These tissues were resistant to ordinarily effective stimulants of acid secretion (histamine, theophyline, dibutyryl cyclic AMP, and gastrin) by rabbit mucosa. Across antral mucosa, net Na transport was inhibited, and net Cl transport was reduced in the presence of alcohol. The unidirectional fluxes of both ions were increased as was permeability to erythritol. These effects of alcohol did not require the presence of acid in the lumen. The rate of luminal acid loss by antrum was increased by alcohol. Addition of ouabain alone, which inhibits net Na and Cl transport, did not alter the rate of luminal acid loss by antrum. Alcohol, however, still increased the rate of luminal acid loss by antral mucosa treated with ouabain. Alcohol reduced the electrical resistance of fundic and antral mucosa but had no effect on the rate of luminal acid loss or electrical resistance of esophageal mucosa. Luminal application of alcohol inhibits active ion transport in addition to increasing cation and anion permeability. However, inhibition of active transport per se is not necessarily associated with an increase in mucosal permeability.
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PMID:Effects of alcohol on ion transport by isolated gastric and esophageal mucosa. 124 81

We studied the functional coupling between antral somatostatin and gastrin cells in pigs using isolated perfused preparations of the antrum with intact supply of the vagus nerves. Luminal acidification significantly inhibited gastrin secretion to 61 +/- 3% of basal secretion and increased somatostatin output 9-fold. Intra-arterial infusion of somatostatin to concentrations of 10(-10) and 10(-9) mol/l inhibited gastrin secretion to 18 +/- 9 and 33 +/- 11% of basal secretion. Electrical stimulation of the vagus nerves and intra-arterial infusion of gastrin-releasing polypeptide (GRP; 10(-9) mol/l) significantly increased both gastrin and somatostatin secretion. Addition to the perfusate of Fab fragments of somatostatin antibodies abolished the effect of somatostatin at 10(-10) mol/l and the acid inhibition of gastrin secretion, but had no effect on the response to vagus stimulation of GRP infusion. We conclude that a local release of somatostatin is essential for the acid-induced inhibition of gastrin secretion, whereas changes in the local somatostatin concentration are unlikely to play a major role in vagally or GRP-induced gastrin secretion.
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PMID:Somatostatin is an essential paracrine link in acid inhibition of gastrin secretion. 135 90

In the present study we developed an experimental model for direct assessment of antral endocrine cell and cholinergic neural responses to luminal stimulation. A sleeve of antral mucosal/submucosal tissue was prepared from rat antrum, mounted in perfusion chamber, and perfused in both luminal and submucosal compartments. Morphological and functional integrity of the antral sleeve were confirmed by histological examination and measurement of protein synthesis. Antral gastrin release was assessed in response to luminal stimulation with acid, peptone and distension. Luminal acid (pH3) inhibited basal gastrin release by -70.4% and luminal peptone stimulated gastrin release to 210% above control (p < 0.02). Distention of the antral sleeve by hydrostatic pressure (3-25cm H2O) caused stepwise and significant increase in gastrin release that was reversible. 3H-acetylcholine was stimulated significantly by KCl (56mM) to values twice control. In summary, these results establish the integrity and responsiveness of the antral sleeve to pharmacological and luminal stimulation. The antral sleeve may be a useful model in assessing antral function in response to luminal stimulation.
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PMID:Validation of the antral mucosal/submucosal sleeve preparation: studies of gastrin and acetylcholine release in response to luminal stimulation. 140 54

The midportions of rat small intestines were resected by 90 per cent, and the residual intestines studied for the effects of diet on mucosal morphology, nutrition and gastrointestinal hormones. Groups of rats were fed chow, an elemental diet (ED), or an ED + dietary fiber (EDF) for 1 or 3 weeks. Nonresected rats which were fed chow or ED for 3 weeks were used as controls. Nutritional parameters, such as concentrations of serum total protein, albumin and transferrin were favorable but gain in body weight was not. The parameters indicated that resected rats fed EDF fared better than resected rats fed ED. Mucosal villous height in the residual jejunum, similar in all the resected groups after 1 week, was significantly increased in the resected rats fed chow or EDF after 3 weeks, but did not differ between 1 and 3 weeks in the resected rats fed ED. Changes in the number of villous epithelial cells and villous width were also examined. The level of plasma enteroglucagon was high in the rats fed chow or EDF after both 1 and 3 weeks, and was positively correlated with the increases in villous height. Levels of serum gastrin were not affected by dietary change. Luminal nutrients were significantly associated with the adaptive changes in the mucosa of the residual intestine, and mucosal morphology was also considerably influenced by dietary change.
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PMID:The effects of diet on the residual small intestine following massive resection. 284 19

Acid production is a major gastric function. Second messengers (cyclic AMP and calcium) are released when parietal cell membrane receptors (H2, muscarinic and gastrin) are stimulated. The second messengers then stimulate the 'gastric proton pump' to produce hydrogen ions. New evidence suggests that there is a unidirectional flux of hydrogen ions into the lumen induced by unique physical properties of mucus and a sodium gradient from lumen to serosa. Luminal hydrogen ions, bile salts, ingested drugs, and ingested alcohol are potential gastric epithelial toxins. The stomach's protective mechanism includes a well-defined mucus layer, an epithelial bicarbonate secretion, a tight epithelium, and a good nutrient blood supply. Endogenous prostaglandins partly control these mechanisms. Modern therapeutics are increasingly directed towards improving gastric cytoprotection.
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PMID:Pathogenesis of peptic ulcer disease and gastritis: importance of aggressive and cytoprotective factors. 353 15

Luminal nutrition is known to have a trophic effect on small bowel mucosa after intestinal resection. Humoral agents, however, may also contribute to this process. Two of the proposed humoral agents, enteroglucagon and gastrin, were therefore investigated after intestinal resection and transection in the rat, and changes in their concentration in the plasma were related to cellular proliferation. Forty-eight male Wistar rats had either 75 per cent proximal small bowel resection or jejunal transection. The animals were further divided into three groups, each with a different nutritional intake. The first group were allowed food ad libitum. The second group were kept under hypothermic conditions which resulted in hyperphagia, while the last group were nourished intravenously. A further 8 animals had a laparotomy only (sham operation). All animals were killed 12 days after operation, plasma enteroglucagon and gastrin were measured, while determination of the crypt cell production rate (CCPR) was used to denote cellular proliferation. In each group resected rats had significantly higher crypt cell production rates and greater enteroglucagon levels compared with transected animals. However, only in the normally fed group was plasma gastrin increased in resected animals, there being no significant difference in the plasma concentration of this peptide in transected compared with resected rats, in both the intravenously fed and hyperphagic groups. In the models studied enteroglucagon appears to be a more likely candidate for a humoral trophic agent than gastrin in intestinal adaptation.
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PMID:The effect of altered luminal nutrition on cellular proliferation and plasma concentrations of enteroglucagon and gastrin after small bowel resection in the rat. 705 95

The regulation of cholecystokinin (CCK) and gastrin release in the chicken and their endogenous actions are summarized. Both dietary protein and amino acids stimulated CCK releases. Among dietary fat sources, medium-chain triacylglycerol (MCT) was a potent stimulator of CCK release compared with long-chain triacylglycerol (LCT). However, it is difficult to explain that endogenous CCK released by those stimulators has an important role in the avian gastrointestinal physiology. Luminal acids may be an important regulator in pancreatic enzyme and fluid secretion. Gastrin (a regulator of luminal acid secretion) release was stimulated by food components, strongly by MCT, but not by LCT, and weakly by some amino acids, and was inhibited by luminal acids. Luminal acids controlled food passage from the crop. In conclusion, gastrointestinal physiology may be directly regulated by luminal acid rather than by the gastrin/CCK family in the chicken.
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PMID:Release and endogenous actions of the gastrin/cholecystokinin (CCK) family in the chicken. 1006 39

The calcium-sensing receptor (CaR) is the major sensor and regulator of extracellular Ca(2+), whose activity is allosterically regulated by amino acids and pH. Recently, CaR has been identified in the stomach and intestinal tract, where it has been proposed to function in a non-Ca(2+) homeostatic capacity. Luminal nutrients, such as Ca(2+) and amino acids, have been recognized for decades as potent stimulants for gastrin and acid secretion, although the molecular basis for their recognition remains unknown. The expression of CaR on gastrin-secreting G cells in the stomach and their shared activation by Ca(2+), amino acids, and elevated pH suggest that CaR may function as the elusive physiologic sensor regulating gastrin and acid secretion. The genetic and pharmacologic studies presented here comparing CaR-null mice and wild-type littermates support this hypothesis. Gavage of Ca(2+), peptone, phenylalanine, Hepes buffer (pH 7.4), and CaR-specific calcimimetic, cinacalcet, stimulated gastrin and acid secretion, whereas the calcilytic, NPS 2143, inhibited secretion only in the wild-type mouse. Consistent with known growth and developmental functions of CaR, G-cell number was progressively reduced between 30 and 90 d of age by more than 65% in CaR-null mice. These studies of nutrient-regulated G-cell gastrin secretion and growth provide definitive evidence that CaR functions as a physiologically relevant multimodal sensor. Medicinals targeting diseases of Ca(2+) homeostasis should be reviewed for effects outside traditional Ca(2+)-regulating tissues in view of the broader distribution and function of CaR.
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PMID:Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion. 2087 97

Luminal amino acids and lack of luminal acidity as a result of acid neutralization by intragastric foodstuffs are powerful signals for acid secretion. Although the hormonal and neural pathways underlying this regulatory mechanism are well understood, the nature of the gastric luminal pH sensor has been enigmatic. In clinical studies, high pH, tryptic peptides, and luminal divalent metals (Ca(2+) and Mg(2+)) increase gastrin release and acid production. The calcium-sensing receptor (CaSR), first described in the parathyroid gland but expressed on gastric G cells, is a logical candidate for the gastric acid sensor. Because CaSR ligands include amino acids and divalent metals, and because extracellular pH affects ligand binding in the pH range of the gastric content, its pH, metal, and nutrient-sensing functions are consistent with physiologic observations. The CaSR is thus an attractive candidate for the gastric luminal sensor that is part of the neuroendocrine negative regulatory loop for acid secretion.
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PMID:Mechanisms of intragastric pH sensing. 2093 60


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