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)

AR42J, a rat pancreatic cell line expressing receptors for both gastrin and epidermal growth factor (EGF), has been used to examine the effect of the gastrin receptor antagonist CR2093 on basal, gastrin-17 (G17), EGF and transforming growth factor (TGF)-alpha stimulated growth in vitro. In serum-free conditions, CR2093 reduced the basal growth of AR42J at a concentration known to displace physiological levels of G17 from gastrin receptors and this effect was reversed by G17 at 1 x 10(-9) M. Alone, G17 had little effect on growth, but EGF and TGF-alpha stimulated growth to 181 and 176% of control values, respectively, and marked synergy was observed when G17 was used in combination with both EGF (212%) and TGF-alpha (259%). When CR2093 was added, the synergistic effects of the G17/EGF and G17/TGF-alpha combinations were reduced to basal levels. In addition, CR2093 inhibited the growth stimulation induced by EGF and TGF-alpha alone. When the ability of CR2093 to bind to EGF receptors was assessed in a ligand binding assay, it was found that the antagonist displaced up to 23% of labeled EGF. Thus CR2093 has potent inhibitory effects on the basal growth of AR42J which can be reversed by G17. It can also inhibit type 1 growth factor-stimulated growth, but although this action may in part be related to the antagonist's ability to inhibit binding to the EGF receptor, other mechanisms may be involved.
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PMID:Inhibitory effects of the gastrin receptor antagonist CR2093 on basal, gastrin-stimulated and growth factor-stimulated growth of the rat pancreatic cell line AR42J. 785 92

The presence of growth factors and their receptors in human midgut carcinoids and in gastric carcinoids of Mastomys have been investigated. Human midgut carcinoid tumours produce IGF-I as demonstrated by immunocytochemistry and radioimmunoassay. IGF-I receptors were detectable in half of the tumours and stimulation of cultured tumour cells with IGF-I enhanced DNA synthesis. IGF-I may therefore act as an autocrine stimulator of carcinoid tumour growth. Expression of TGF-alpha and EGF-receptors could also be demonstrated in midgut carcinoids by immunocytochemistry and Northern analysis, suggesting that TGF-alpha participates in the autocrine modulation of carcinoid growth. Co-culture of human midgut carcinoid tumours and rat fetal cholinergic neurons demonstrated secretion of a potent neuronotrophic factor by cultured tumour cells. IGF-I and TGF-alpha may account for these neuronotrophic effects, but carcinoid tumours may also secrete an as yet unidentified growth factor. Gastric (ECL cell) carcinoids developed rapidly in Mastomys during hypergastrinemia due to histamine2-receptor blockade, suggesting that gastrin is an essential growth factor for these carcinoids.
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PMID:Growth factors and carcinoid tumours. 832 52

Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) bind to a common receptor and are both present in the normal gastrointestinal tract. Although many studies have examined their function in isolation, there is little information directly comparing their actions. We examined the relative potency of TGF alpha and EGF in stimulating 3H-thymidine uptake into primary rat hepatocytes at various doses in vitro and on the crypt cell production rate (CCPR) within the gastrointestinal tract when infused intravenously at 49 nmol/kg/day into rats receiving total parenteral nutrition. In vitro, maximal stimulatory activity was similar in EGF- and TGF alpha-treated cells, however, the dose of EGF required to stimulate 3H-thymidine uptake to 50% of maximal levels was only one third of that required using TGF alpha. In vivo, EGF and TGF alpha significantly increased the weight and proliferative indices throughout the gastrointestinal tract. The response (as determined by CCPR) was about 80% higher in animals which had received EGF when compared to animals receiving TGF alpha. Treatment with EGF also caused significant rises in plasma PYY, enteroglucagon and gastrin levels, whereas the equivalent dose of TGF alpha only caused a significant rise in plasma gastrin levels. We conclude that TGF-alpha, like EGF, is trophic to the entire gastrointestinal tract of the rat, however, it is a less effective mitogen, and has differential hormonal effects.
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PMID:Comparison of the effects of transforming growth factor alpha and epidermal growth factor on gastrointestinal proliferation and hormone release. 888 81

ILA cells were established from tumors induced by the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) in hamster islets. The proliferation, morphology, karyotype, immunoreactivity with certain antibodies and growth factor secretion of these tumor cells were compared with the same parameters in tumor cells induced by BOP in hamster ductal cells (TAKA-1-BOP) established in a previous study. Minor differences were found in the morphology and ultrastructure of the 2 cell lines. Contrary to TAKA-1-BOP cells, ILA cells did not express cytokeratins 8.13, 13 or 18 but did express DU-PAN-2 and TAG-72, 2 known human pancreatic cancer-associated antigens. No endocrine cell markers were expressed. A significant difference also was found in the chromosomal pattern in that there were more abnormalities and marker chromosomes in ILA cells than in TAKA-1-BOP cells and the Y or X chromosomes were missing in ILA cells. ILA cells produced TGF-alpha, IGF-I, bombesin and gastrin and expressed specific binding sites for hEGF. TGF-alpha secretion from ILA cells was much greater than that from TAKA-1-BOP cells. Our results indicate that pancreatic cancer cells grown in vitro are not a single clone. We conclude that there are some genetic and biological differences between tumors arising from pancreatic duct and islets and that pancreatic ductal adenocarcinomas originating from islets have a profound malignant potential.
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PMID:Establishment of tumor cell culture (ILA) derived from hamster pancreatic islets treated with BOP. 980 35

The increase in the aging population has led to a growing interest in achieving a better understanding of the aging process and of diseases that are predominantly expressed during advancing age. Since the structural and, in turn, the functional integrity of the mucosa of the gastrointestinal tract (GI) are maintained by constant renewal of cells, a detailed knowledge of the events that initiate and regulate mucosal proliferative processes is essential for a better understanding of the normal aging process as well as age-associated dysfunctions, including malignancy that represent disorders of tissue growth. In Fischer-344 rats, aging is associated with increased mucosal proliferative activity in much of the GI tract. On the other hand, the functional properties are either decreased or remain unchanged during advancing age. Basal gastric acid and pepsin output decline during aging, as is gastrin secretion. In contrast, antral gastrin levels increase during this period, as is mucosal histidine decarboxylase activity. The age-related decline in gastrin secretion could partly be attributed to a higher ratio of somatostatin (D) to gastrin (G) cells in the antral mucosa. The age-related rise in GI mucosal proliferative activity could not be attributed to the trophic action of either gastrin or bombesin, since they caused no significant change in mucosal proliferation in aged rats. On the other hand, EGF and TGF-alpha appear to be involved in regulating mucosal proliferation during aging. Aging is associated with increased activation of EGF-receptor (EGFR), the common receptor for EGF and TGF-alpha. This could be due to (a) increased levels of membrane-bound precursor form(s) of TGF-alpha resulting in increased activation EGFR signaling processes through an autocrine/paracrine mechanism, (b) heightened sensitivity of mucosal EGFR to EGF and TGF-alpha such that comparatively lower levels of these peptides are required to activate EGFR in aged than in young animals and/or (c) loss of EGFR regulatory factor(s) such as ERRP (EGFR Related Protein), a "negative regulator" of EGFR.
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PMID:Regulation of gastrointestinal mucosal growth during aging. 1507 56

In this paper the authors focus attention on the role of gastrin as a carcinogenic factor. The aim was to bring together the numerous controversial studies on this subject, adding the authors' own personal clinical experience. Gastrin (G) is responsible for the development of carcinoids, as has been experimentally shown in Mastomys rats, and more recently in man. This hormone is regarded as a mitogen for cells in the gastroenteric tract; it acts through specific reactors and messengers, including AMPc and protein kinase A (PKA). Its role in the development of other neoplasias of the gastroenteric tract appears to be linked, but not always subordinate, to the presence of growth factors such as: EGF and TGF-alpha, and also to the possible stimulation of oncogens induced by hypergastrinemia.
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PMID:[Gastrin and gastrointestinal neoplasias]. 1649 5

The physiological processes leading to the expression of the resilient phenotype, which allow animals to maintain a relatively higher production level during infection, have been investigated in lambs from a closed flock selected for 40 generations for high fleece weight (HFW), but with higher FEC and worm burdens than their unselected control (C) flock run in parallel. After recovery from surgery to implant abomasal cannulae, eight parasite-naive lambs from each flock were infected intraruminally at 4.5 months-of-age with 50,000 Teladorsagia circumcincta L3. Blood, abomasal fluid and faecal samples were collected daily for measurement of serum gastrin and pepsinogen concentrations, blood eosinophils, abomasal pH and FEC. Four lambs from each flock were euthanased on Day 8 post-infection and the other four on Day 28 post-infection. At necropsy, abomasal contents and tissues were collected for worm counts, abomasal lymph nodes and fundic tissue for cytokine gene expression and fundic tissue for histopathology. Expression of resilience appeared to be age-dependent as there were no significant differences in either FEC or worm burden between lambs from the two flocks, unlike older HFW lambs in a previous study. Abomasal secretion did not differ between flocks. Histopathological changes were typical of parasitism: inflammatory cells, mainly eosinophils and lymphocytes, were numerous in nodular areas and there were fewer TGF-alpha positive parietal cells, many of which were vacuolated. By Day 28 p.i., globule leucocytes were present. Mucosal thickness was significantly greater on Day 8 than Day 28 p.i. (p=0.000) and in C than HFW lambs. There were fewer parietal cells on Day 28 than on Day 8 p.i. (p=0.003) for pooled data. Circulating eosinophil counts increased moderately in both groups, significantly less in the HFW lambs. Fewer tissue and blood eosinophils in the HFW than C group on Day 8 p.i. were consistent with cytokine gene expression patterns, particularly lower IL-5 levels. Worm count decreased by 90% by Day 28 p.i., along with declining tissue eosinophil counts and IL-13 gene expression and increasing IL-10 and IL-4 gene expression. Food intake was depressed less in the HFW lambs, suggesting that maintenance of appetite could be an important aspect of the physiological basis for resilience. Although the resilient phenotype was not apparent at the younger age, lesser effects on food intake, differences in ALN cytokine profiles and lower blood and tissue eosinophil numbers in the HFW lambs may lead to the expression of resilience when older.
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PMID:Effects of Teladorsagia (Ostertagia) circumcincta infection on lambs selected for high fleece weight. 1967 87