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)

Thyrocalcitonin (TCT) is a 32 amino acid peptide hormone similar, but not identical, in structure from fish to man. Mammals produce the hormone in non-follicular thyroidal "C-cells" which can be identified visually using recently developed immunocytochemical methods. Although TCT exerts effects on the gut and kidney, bone seems to be the primary target tissue. The ability of TCT to restrict calcium fluxes from bone to blood and to inhibit bone resorption explains its utility for treating certain metabolic bone diseases, e.g. Paget's disease. The bone effects also account for the ability of TCT to combat a hypercalcemic challenge. Recent work suggests close relationships and a possible closed-loop feedback system between the gut and thyroid. In animals, gastrin is a potent TCT secretagogue; studies in man indicate that TCT, in turn, can effect gastric acid secretion and intestinal secretion of water and electrolytes. This gastrin-TCT relationship may help control levels of blood calcium during intestinal absorption of calcium following feeding. The ability of gastrin to stimulate TCT release has been applied clinically for the early diagnosis of medullary thyroid carcinoma (MTC), a C-cell tumor. Subclinical or questionable cases of MTC have been identified reliably using a simple, rapid provocative test involving pentagastrin injection and evaluation of blood samples by radioimmunoassay for elevated levels of TCT.
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PMID:Recent advances with thyrocalcitonin. 125 62

To determine the effect of intraduodenal calcium on pancreatic, gallbladder, and gastric functions in healthy man, a validated perfusion method was employed to quantify total pancreatic, biliary, and gastric outputs during duodenal perfusion of either 6 mM, 12 mM,or 25 mM of elemental calcium (as isotonic calcium chloride solutions). Intraluminal calcium stimulated pancreatic enzyme secretion and gallbladder contraction in a dose-related fashion, achieving comparable responses to those produced by intravenous cholecystokinin-pancreozymin (CCK-z). Responses to calcium were reproducible when repeated in the same individual. Gastric acid outputs and serum gastrin levels increased significantly only with higher calcium perfusions (25 mM). Although duodenal calcium perfusion (25 mM) slightly increased serum calcium concentrations, induced hypercalcemia (by intravenous calcium infusion) of similar magnitude had no effect on pancreatic or gallbladder function. It is suggested that intraduodenal calcium may induce release of CCK-PZ (and/or other neurohormonal factors) from the gut, causing stimulation of these digestive organs.
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PMID:Pancreatic, gallbladder, and gastric responses to intraduodenal calcium perfusion in man. 126 60

The distribution of neurotensin-, substance P-, gastrin/cholecystokinin/carerulein- and bombesin-like immunoreactivities has been studied in the gut of the tilapia (Oreochromis mossambicus) and the goldfish (Carassius auratus) using immunohistochemistry and radioimmunoassay; the electrophysiological effects of these peptides on the intestinal epithelium were also examined with the Ussing-type chamber technique. Neurotensin- and gastrin/cholecystokinin/caerulein-like immunoreactivities were present in endocrine cells in both species. Substance P- and bombesin-like immunoreactive endocrine cells were present in the intestine of the tilapia. Neurotensin-like immunoreactivity was observed in varicose fibers and nerve cell bodies in the muscle layers and myenteric plexus of both species, whereas nerve fibers showing substance P-like immunoreactivity were found in the goldfish only. Using radioimmunoassays, neurotensin- and gastrin/cholecystokinin/caerulein-like immunoreactive materials were detected in intestinal extracts of both species. The amounts of substance P- and bombesin-like material were below detection level. The ion selectivity of the intestinal epithelium of both species was modulated by exogenously applied neurotensin. This effect was blocked by tetrodotoxin in the tilapia but not in the goldfish. In the tilapia, neurotensin may act via stimulation of a cAMP-dependent increase of the Cl- conductance of the tight junctions, whereas in the goldfish, neurotensin induced, via an unknown messenger, a transient decrease of the cation selectivity without a decrease in the resistance. Substance P, cholecystokinin, and bombesin were without effect on the electrophysiological characteristics of the epithelium.
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PMID:Neurotensin, substance P, gastrin/cholecystokinin, and bombesin in the intestine of the tilapia (Oreochromis mossambicus) and the goldfish (Carassius auratus): immunochemical detection and effects on electrophysiological characteristics. 128 77

The gastric mucosa consists of the epithelium, which lines the lumen, the lamina propria, and the muscularis mucosae. The targets of drugs used to treat stomach and duodenal ulcers are thought to be the acid-secreting parietal cells of the epithelium. However, immune cells in the lamina propria are the only cells that showed detectable messenger RNAs for histamine, muscarinic, gastrin, and dopamine receptors by in situ hybridization histochemistry. None of the epithelial cells expressed any of these messenger RNAs. Thus, the targets of antiulcer drugs seem to be cells of the immune system in the gut and not parietal cells, as generally believed. This conclusion may revise the thinking about ulcer formation and may shed light on the etiology of such chronic small intestinal diseases as Crohn's disease.
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PMID:Localization of targets for anti-ulcer drugs in cells of the immune system. 133 41

This article describes studies with four peptides, epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), gastrin-releasing peptide/bombesin (GRP), and gastrin. The mitogenic and anti-secretory activities of EGF/TGF alpha appear to be mediated by a single class of high-affinity membrane receptors but may involve different signal transducing mechanisms. Biological activity of EGF resides in the N-terminal 42 amino acid fragment with the C-terminal undecapeptide determining binding affinity. A parenteral depot formulation of an EGF-related peptide or a small molecule agonist of the EGF receptor could have utility in treating various ulcerative disorders of the gut. Although antagonism of EGF (and thus TGF alpha) receptors and/or transducing mechanisms is frequently cited as a potential therapeutic approach to hyperproliferative diseases, blocking the action of TGF alpha, GRP, or gastrin with neutralizing antibodies or receptor antagonists did not influence the growth of a wide range of solid tumors in nude mice. These findings suggest that, unless tumor growth displays absolute dependency on one particular mitogen, antagonism of a specific growth factor is unlikely to have great effect in cancer therapy.
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PMID:Therapeutic potential of growth factors and their antagonists. 134 Oct 74

Growing recognition that there exists a functionally important brain-gut axis has prompted several research groups to examine more closely the role of central nervous system factors in gastric mucosal injury. Less attention has been directed toward brain regulation of defensive factors in the gut. Toward that end, we have been characterizing a growing role for dopamine as an important mediator of gastric defense. New data suggest that dopamine, and other substances including many peptides as well as interleukin, act not only to reduce aggressive elements which promote gastric mucosal injury (gastric acid, pepsin, gastrin, leukotrienes) but also to augment defensive factors which retard ulcerogenesis (mucus, bicarbonate, prostaglandins, free radical scavenging enzymes, vasodilators/relaxers). Increasing attention should be directed toward the often-neglected defensive aspect of gastric mucosal ulcerogenesis and protection.
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PMID:Brain-gut relationships: gastric mucosal defense is also important. 134 78

The effects of the first meals on the release of seven gut regulatory peptides were studied in newborn calves fed colostrum either at serial intervals during the first day of life or at 28 h only. Fasted animals showed no significant variation of plasma peptides until the first feed, except for somatostatin, which peaked at 4-5 h and declined thereafter. As assessed before and 1 h after feeding, the first meal tended to induce rises in plasma gastrin, cholecystokinin and pancreatic polypeptide, while the other peptides were unaffected. Repeated colostrum feeds induced marked increases in plasma gastrin, cholecystokinin, secretin and vasoactive intestinal peptide from 10 h on. Pancreatic polypeptide was transiently increased from 4 to 16 h. Feeding was followed by a transitory reduction of plasma somatostatin and by a prolonged decrease of plasma motilin. We conclude that colostrum feeding potently modulates the release of several regulatory peptides shortly after birth in calves. These responses may be important for the adaptation of gut growth, secretions and motility to food ingestion in the neonatal period.
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PMID:Early-life patterns of plasma gut regulatory peptide levels in calves: effects of the first meals. 134 58

1. The effects of age, weaning and feeding on the release of seven gut regulatory peptides [gastrin, cholecystokinin (CCK), secretin, vasoactive intestinal peptide (VIP), pancreatic polypeptide (PP), motilin and somatostatin] were studied in calves either exclusively milk-fed between birth and 91 days (P group) or weaned between 22-56 days of age (R group). 2. During the first 3 weeks, the basal plasma immunoreactive levels increased with age for secretin, CCK and PP, decreased for gastrin, motilin and somatostatin and were unaffected for VIP. The changes were particularly rapid for somatostatin and gastrin. After 3 weeks, no significant trend was observed with age in the P group. 3. Weaning resulted in an increase of basal gastrin, CCK, PP and VIP and in a decrease of basal secretin and somatostatin. 4. In the P group, the morning meal was followed 1 hr later by an increase of gastrin and CCK, and by a fall of secretin, PP, motilin and somatostatin, but no significant effect was observed in VIP. Weaning resulted in a reduction of the differences between the fasting and the post-feeding values. 5. These changes suggest a large involvement of endocrine cells in the adaptation of gut tissues, secretions and motility at birth, during the maintenance at the pre-ruminant stage and at weaning.
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PMID:Early-life patterns of plasma gut regulatory peptide levels in calves. Effects of age, weaning and feeding. 135 17

To clarify changes in gastric acid and gut hormone secretion after pylorus-preserving pancreaticoduodenectomy (PPPD), an experimental study was performed using a model of pylorus-preserving duodenectomy in dogs previously provided with Heidenhain pouch (HP). The duodenectomy involves resection of the duodenum and 10 cm of the proximal jejunum preserving 2 cm of juxtapyloric duodenum and round-shaped duodenal wall around pancreatic papilla. Reconstruction was done by anastomosing the rho-shaped jejunal loop to gallbladder, juxtapyloric duodenum and peripapillar round-shaped duodenal wall with ligation of the common bile duct. For these dogs, intravenous glucose tolerance test (IVGTT), oral glucose tolerance test (OGTT), meal ingestion test (TM) and histological studies of pancreatic specimen obtained at autopsy were performed investigating pancreatic, gastric acid and gut hormone secretion. Preservation of endocrine and exocrine pancreatic secretion after operation demonstrated our experimental model to be adequate for evaluation of the factor of duodenectomy in PPPD on gastric acid and gut hormone secretion avoiding the influences of changes in pancreatic secretion. Postprandial gastric acid secretion from HP did not change significantly after operation. Postprandial secretion of gastrin, glucagon, GIP and enteroglucagon did not alter significantly after operation. These results indicated that in the clinical PPPD procedure, preservation of more than 2 cm of duodenum from the pylorus produced neither postprandial gastric acid hypersecretion, which might be cause of postoperative stomal ulcer, nor any change of related gut hormone secretion.
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PMID:An experimental study on the gastric acid and gut hormone secretion after pylorus preserving duodenectomy in dogs. 135 8

Cysteamine, a potent duodenal ulcerogen, stimulates gastric acid and gastrin secretion and decreases immunoreactive somatostatin (IRS) from the gut and hypothalamus of the rat. To elucidate the structural requirements for this effect, we tested a series of cysteamine analogs for their IRS decreasing activity in comparison with their nucleophilic and reducing potencies. Adult female rats were sacrificed 4 hr after p.o. administration of the test chemicals given in molar equivalents to 30 mg/100 g of cysteamine-HCl. IRS decreasing activity in gastric mucosa, expressed as percentage of controls is listed in descending order: cystamine (55%), cysteamine (59%), 2-dimethylaminethanethiol (59%), ethylamine (66%), 1,3-propanedithiol (70%), propylamine (75%) and 3-aminothiophenol (79%). The following thiols and amines had no IRS decreasing effect (80% of controls): L-cysteine, ethanethiol, 1-propanethiol, penicillamine, dimercaprol, 1-4-dithiothreitol, ethanolamine, propionitrile, n-butyronitrile, o-, m- or p-aminophenol. The aryl 2-, 3- or 4-aminothiophenols, unlike most of their aminophenol analogs also decreased immunoreactive prolactin in the pituitary by 38 to 78%. IRS decreasing activity was independent of the reducing potency of cysteamine derivatives but was correlated significantly (r = 0.793, P < .01) with electron affinity of -SH, -NH2, -OH and -CN radicals in terminal alkyl chemicals. The structural requirement for decreasing activity is the presence of either -SH and -NH2 on a 2 to 3 carbon alkyl or aryl molecule. Both radicals when present together increase potency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin depleting potency of cysteamine-related thiols and amines in the rat: structure-activity relation. 135 14


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