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)

We have investigated the effects of melatonin (Mel) and N-acetylserotonin (NAc-5HT) on the mitotic activity of gastric and colonic mucosa in adult male rats under basal conditions and after an administration of omeprazole (OM) (H+,K(+)-ATPase inhibitor). The metaphase-arrest technique was applied in the study. Additionally, serum gastrin levels were measured by RIA method in the OM-treated group and in respective polyethyleneglycol (PEG)-administered controls. We have found that: 1) OM-treatment increased serum gastrin levels in rats; 2) OM enhanced the mitotic activity of the colonic mucosa cells, although, unexpectedly, it did not exert such an effect on the gastric mucosa cells; 3) Mel suppressed the OM-induced increase of the colonic epithelium cell proliferation, while NAc-5HT failed to reveal that action: 4) NAc-5HT decreased the proliferation of gastric mucosa epithelial cells. The value of the mean mitotic activity rate (MMAR) of gastric mucosa after Mel-treatment also decreased, but that change was not statistically significant. The obtained data are in compliance with previous results from our laboratory concerning the inhibitory effect of pineal indoleamines on the jejunal epithelium mitotic activity. The stimulatory effect of OM on the proliferation of colonic epithelium is probably mediated by OM-induced hypergastrinaemia. The possibility of Mel interaction with intestinal gastrin receptors (a structural similarity occurs between Mel and benzotript, a specific gastrin receptor antagonist), as well as of the opposite effects of Mel and gastrin on intracellular cAMP content in the gut, are considered in the discussion of results.
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PMID:Influence of pineal indoleamines on the mitotic activity of gastric and colonic mucosa epithelial cells in the rat: interaction with omeprazole. 205 33

The mechanism whereby gastrin triggers phosphoinositide breakdown was investigated in an enriched preparation of isolated rabbit parietal cells (approx. 75%). In a permeabilized preparation of myo-[3H]inositol-labelled cells, GTP[S], a non-hydrolysable GTP analogue, enhanced [3H]inositol trisphosphate ([3H]InsP3 accumulation in a dose-dependent manner; submaximal concentrations of GTP[S] (less than 10 microM), potentiated gastrin-induced [3H]InsP3 release; preincubation for 5 min with GDP[S], a non-hydrolysable GDP analogue, dose-dependently reduced [3H]InsP3 accumulation stimulated by gastrin even in presence of GTP[S]. Exposure of intact parietal cells for 3 h to pertussis toxin (PTx) (200 ng/ml) led to a 15-50% reduction in gastrin-induced [14C]aminopyrine [(14C]AP) uptake (an index of in vitro acid secretion) and [3H]inositol phosphate ([3H]InsP) accumulation. A decrease in the accumulation of the different [3H]inositol phosphate occurred in gastrin-stimulated parietal cells treated with PTx. A rightward shift of gastrin dose-response curves in the presence of PTx was observed for [14C]AP uptake (EC50 values: 0.125 +/- 0.045 nM without PTx and 1.05 +/- 0.63 nM with PTx), for [3H]InsP accumulation (EC50 values: 0.16 +/- 0.08 nM without PTx and 1.56 +/- 0.58 nM with PTx) and [125I]gastrin binding (IC50 values: 0.247 +/- 0.03 nM without PTx and 2.38 +/- 0.56 nM with PTx). In contrast, cholera toxin (CTx) treatment (100 ng/ml) for 3 h was without effect on gastrin-induced [3H]InsP accumulation. CTx induced a pronounced potentiation of gastrin-stimulated [14C]AP uptake; this effect can be mimicked by IBMX (a phosphodiesterase inhibitor) and by forskolin (an activator of adenylyl cyclase). We conclude that: (i) one or more than one G protein appeared to be involved in gastrin receptor coupling to phospholipase C (PL-C); (ii) these G proteins are not substrates for CTx; (iii) one of these appeared to be a PTx-sensitive 'Gi-like' protein which could be involved in hormone-induced acid secretion, (iiii) the potentiating effect of CTx observed on AP uptake stimulated by gastrin suggests the existence of a cooperative effect between cAMP pathway (CTx) and the gastrin-induced phosphoinositide breakdown in acid secretory activity of parietal cells.
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PMID:Involvement of a pertussis toxin-sensitive G protein in the action of gastrin on gastric parietal cells. 212 30

Gastric cancer remains a disease with a very poor prognosis, and there is no safe and effective form of therapy for advanced disease. Evidence is now abundant to show that gastrin stimulates the growth of both gastric and colorectal cancer cells in vitro and in vivo, and that blockade of gastrin receptors can prolong survival in xenografted nude mice. We have thus performed a randomized, controlled study of the gastrin/cholecystokinin receptor antagonist proglumide as therapy in 110 patients with gastric carcinoma. Proglumide had no overall effect on survival (Mantel-Cox statistic = 0.5, P = 0.48). The 95% confidence interval for the proglumide treated group was 260 to 474 days compared to 230 to 372 days for the control group. No significant difference was seen with proglumide, which has a relatively low affinity with the gastrin receptor and also has partial agonist activity. Drugs that are far more specific and potent gastrin receptor antagonists are becoming available, which may have a greater effect on survival, and further clinical trials of such compounds are clearly indicated to determine the efficacy of hormonal control of gastrointestinal malignancy.
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PMID:The effect of the gastrin receptor antagonist proglumide on survival in gastric carcinoma. 220 95

Novel aryl amide analogues of glutamic acid dialkylamide have been synthesized to test for a possible structural analogy between glutamic acid and benzodiazepine CCK antagonists such as compounds 2 and 24 (lorglumide and MK-329, respectively). In support of the structural model, certain of these hybrid compounds are more potent in pancreas CCK radioligand binding assays than corresponding lorglumide-type reference compounds. Modifications previously found in the benzodiazepine antagonists to result in brain CCK/gastrin receptor selectivity were also incorporated to produce an aryl urea series of glutamic acid analogues. None of these compounds were brain CCK/gastrin selective; however, one was potent and selective in the pancreas binding assay. The model appears to be most useful in the design of selective ligands for the pancreas type CCK receptor.
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PMID:Novel glutamic acid derived cholecystokinin receptor ligands. 229 27

Receptors for the brain and gut peptide cholecystokinin (CCK) have been classified into two classes, CCK-A and CCK-B. To date, peptide analogues with selectivity for the CCK-B receptors have been identified, and selective antagonists for CCK-A and CCK-B receptors have been reported as well; until now, there have been no reports of highly selective CCK-A agonists. Herein we describe the properties of A71378 [desamino-Try(SO3H)-Nle-Gly-Trp-Nle-(N-methyl)Asp-Phe-NH2], a highly selective CCK-A receptor ligand. Characterization of A71378 was carried out in the guinea pig pancreas, cortex, gastric gland, and ileum, as well as in NCI-H345 cells. The IC50 values of A71378 for the pancreatic CCK-A, cortical CCK-B, and gastrin receptor were 0.4 nM, 300 nM, and 1,200 nM, respectively. A71378 proved to be a potent agonist in eliciting pancreatic amylase secretion (EC50 = 0.16 nM) and ileal muscle contraction (EC50 = 3.7 nM). In contrast, A71378 was relatively weak (EC50 = 600 nM) in mobilizing intracellular calcium from NCI-H345 cells, which express CCK-B/gastrin receptors. The high potency and selectivity of A71378 for the CCK-A over CCK-B and gastrin receptors is unprecedented among CCK peptides. Studies on CCK-7 analogues indicate that N-methylation of the Asp residue is responsible for the observed selectivity for CCK-A receptors. This discovery of a selective CCK-A agonist should prove valuable for studies aimed at understanding the physiological roles of CCK-A receptors in the brain and periphery.
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PMID:A71378: a CCK agonist with high potency and selectivity for CCK-A receptors. 233 77

With regard to the structural analogies between the C-terminal tetrapeptide of gastrin, gastrin receptor antagonists and anticancer derivatives of glutamine, it is plausible to propose that the mechanism of the anticancer activity may be related to interaction with the gastrin receptor. Dietary glutamine intake and glutamine metabolites may also influence the activity of gastrin receptors.
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PMID:Glutamine derivatives as novel anticancer agents acting via gastrin binding sites. 237 92

Smooth muscle cells isolated from the longitudinal muscle layer of guinea pig ileum were used to determine the presence and type of cholecystokinin/gastrin receptor mediating contraction. This was accomplished with a series of cholecystokinin and gastrin agonists (CCK-8, des(SO3)CCK-8, gastrin-17, des(SO3)gastrin-17 and pentagastrin) and antagonists (glutaramic acid derivatives CR 1392, CR 1409, CR 1505 and proglumide). The order of potency of agonists based on EC50 values derived from concentration-response curves was: CCK-8 greater than des(SO3)CCK-8 greater than gastrin-17 greater than des(SO3)gastrin-17. The inhibitory dissociation constant (Ki) for the antagonist CR 1505 derived from Schild plots was the same whether sulfated CCK-8 or desulfated gastrin-17 was used as agonist (4.47 +/- 0.76 versus 4.68 +/- 0.78 nM). Pentagastrin acted as a partial agonist and inhibited partially the response to CCK-8. The Ki values determined for all antagonists with pentagastrin as agonist were similar to those with CCK-8 as agonist. The order of potency of agonists and the independence of Ki values from the type of agonist used implied that CCK and gastrin interact with one receptor type; the receptor is more sensitive to CCK-8 but is minimally influenced by sulfation of the tyrosine residue. In this respect, the receptor appears to be distinct from the CCK receptor on gallbladder muscle cells and pancreatic acinar cells.
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PMID:Receptor type for cholecystokinin on isolated intestinal muscle cells of the guinea pig. 237 45

Patients with Addisonian pernicious anaemia are alleged to generate antibodies directed against the gastrin receptor. We purified IgG from 15 patients with pernicious anaemia and 15 healthy controls in an effort to show attenuation of gastrin specific binding in vitro and inhibition of gastrin stimulated acid secretion in vivo. Binding of the IgG fraction was determined in a radioreceptor assay utilising the rat pancreatic carcinoma cell line AR42J which expresses high affinity gastrin binding sites (Kd = 5 x 10(-10)). In comparison with control serum, there was no significant displacement (p = 0.10) of human gastrin-17 binding by pernicious anemia samples at either 0.3 mg protein/ml (control (mean (SEM)) 1489 (131) cpm; patients 1858 (174) cpm) or 3 mg protein/ml (control 1930 (110); patients 2195 (107) cpm). The effect of intravenous and intragastric IgG on acid secretion in the anaesthetised rat was determined over a 60 minute period after stimulation with 1 microgram/kg human gastrin-17. A bolus injection of IgG (60-200 mg/kg) had no significant effect (p = 0.50) on gastrin stimulated acid output (29.21 (1.28) mumol H+/h) compared with control (27.48 (4.70) mumol H+/h). Similarly, instillation of 800 mg/kg IgG directly into the stomach for 90 minutes also failed to influence gastrin stimulated acid output (29.69 (3.22) mumol H+/h). Thus, we have been unable to confirm previous reports of an IgG from patients with pernicious anaemia capable of blocking gastrin receptor binding or gastrin stimulated acid secretion.
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PMID:Absence of a gastrin inhibitory factor in the IgG fraction of serum from patients with pernicious anaemia. 238 8

Pancreatico-biliary diversion (PBD) stimulates pancreatic growth in the rat. The present experiment was designed to investigate the mechanism of this phenomenon. The potential roles of endogenous CCK, gastrin, and secretin were studied. Hormone measurements by specific RIA's show that PBD was associated with higher CCK plasma concentrations and, conversely, with lower gastrin circulating levels. Secretin and pancreatic polypeptide were unaffected by PBD. Seven days' subcutaneous administration of proglumide (1000 mg/kg/day), benzotript (100 mg/kg/day), two CCK and gastrin receptor antagonists, and Ranitidine (100 mg/kg/day) resulted in a significant inhibition of PBD-induced pancreatic growth, assessed by measurements of pancreatic weight, DNA, RNA and protein content. These results suggest, therefore, that CCK plays a central role in the development of the pancreatic adaptive response to PBD.
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PMID:Mechanism of pancreatic growth induced by pancreatico-biliary diversion in the rat. Inhibition by proglumide, benzotript, and ranitidine. 240 83

Caerulein, CCK8, and gastrin, hormones which interact with the cholecystokinin receptor increased the growth of mouse pancreatic acinar cells in vitro. In contrast, bombesin, substance P, and carbachol, factors which interact with separate receptors, and stimulate pancreatic secretion similarly to CCK by mobilising intracellular Ca2+, did not have any effect on the growth of pancreatic acinar cells in vitro. These results suggest both a unique role for cholecystokinin in the physiological regulation of the pancreas and that the mechanisms that mediate the trophic effects of cholecystokinin are different from those that mediate secretion.
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PMID:Effects of calcium mediated secretagogues on the growth of pancreatic acinar cells in vitro. 244 61


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