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)

A sensitive radioimmunoassay was developed for human epidermal growth factor (hEGF) in saliva and gastric juice. This method was sufficiently sensitive for an accurate measurement of hEGF in these biological fluids. The minimal detectable concentration of EGF was 30 ng/L. The imprecision profile of EGF standard curve had a CV less than 10% in the range of 0.1-3.0 micrograms/L. Serial dilution curves of saliva and gastric juice paralleled that of standard EGF. The antibody to hEGF showed no cross-reactivity with a large excess of growth factors, such as human transforming growth factor alpha, human insulin-like growth factor I, and platelet-derived growth factor (c-sis). No detectable cross-reactivity was observed with some biological gut peptides: somatostatin, gastrin, secretin or pancreatic polypeptide. The intra-assay CV for saliva and gastric juice was less than 10%, and the recoveries were 93.9 +/- 8.7% and 93.7 +/- 11.3%, respectively for saliva and gastric juice. Gel exclusion chromatography revealed hEGF-like substances, heterogeneous in size in saliva and gastric juice, the origins and physiological functions of which are unknown.
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PMID:Radioimmunoassay of epidermal growth factor in human saliva and gastric juice. 204 84

Effects of regulatory molecules on growth of mouse pancreatic acinar cells in culture were examined. The cholecystokinin (CCK) analogue caerulein and cholecystokinin octapeptide (CCK-8) each led to threefold increases in incorporation of [3H]thymidine into DNA. Gastrin, which interacts weakly with the CCK receptor, stimulated DNA synthesis, but only at much higher concentrations. In contrast, other secretagogues that utilize Ca2+ as an intracellular messenger, including carbachol, bombesin, substance P, and the ionophore A23187, did not induce trophic responses. Factors that affect intracellular cAMP concentration, such as secretin, somatostatin, VIP, DBcAMP, and forskolin, did not increase DNA synthesis in cultured pancreatic cells. Insulin and epidermal growth factor induced two- and threefold increases in [3H] thymidine incorporation into DNA, respectively. The effects of insulin were mediated via insulin-like growth factor I receptors. Steroid hormones had little effect on pancreatic acinar cell DNA synthesis. The stimulatory effects of CCK, insulin, and EGF were additive. The combination of caerulein, EGF, and insulin in a hormonally defined medium led to a tenfold increase in the incorporation of [3H]thymidine into DNA. These data indicate that CCK, EGF, and insulin directly increase DNA synthesis in pancreatic acinar cells.
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PMID:Stimulation of pancreatic acinar cell growth by CCK, epidermal growth factor, and insulin in vitro. 302 Sep 92

Effects of gut regulatory peptides and growth factors on the uptake of 2-aminoisobutyric acid (AIB) and 2-deoxy-D-glucose (2-DOG) were examined in differentiated ovine satellite cell cultures. Insulin and insulin-like growth factor I (IGF-I) gave maximal increases of 160-180% of controls for AIB and over 190% for 2-DOG. IGF-I showed half-maximal effects at 0.1-1 nM, and insulin at 1-10 nM. Bovine growth hormone (0.01-100 nM) had no effect. Gastrin, gastric inhibitory polypeptide (GIP), bombesin and somatostatin had no action in either the absence or presence of insulin. In primary cultures epidermal growth factor (EGF) increased the uptake of AIB (133-137%) and 2-DOG (171-176%). In clonal lines, EGF had little effect on nutrient uptake but still simulated protein synthesis.
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PMID:Effects of growth factors and gut regulatory peptides on nutrient uptake in ovine muscle cell cultures. 770 22

The effects of somatostatin analogue RC-160 and bombesin/gastrin releasing-peptide (GRP) antagonist RC-3095 were evaluated in Copenhagen rats bearing the anaplastic, androgen-independent Dunning R3327-AT-1 prostatic adenocarcinoma. In the first experiment, RC-160 was given in the form of microcapsules releasing 60 micrograms/day/rat. RC-3095 was administered from implanted Alzet osmotic minipumps liberating 100 micrograms/day/rat. After 32 days, tumor volumes and weights were significantly reduced by RC-160 as compared with the control group. Tumor doubling time in rats treated with RC-160 was significantly longer than in controls. Bombesin/GRP antagonist RC-3095 also significantly reduced tumor volume after 7 days of treatment, but after 18 days the inhibition in tumor volume was no longer significant. Tumor growth was not suppressed by castration. In the second experiment, 3-mm3 fragments of Dunning R-3327-AT-1 tumor were implanted orthotopically into the prostates of Copenhagen rats in order to evaluate the survival time of animals bearing this cancer during treatment with RC-160 released from Alzet osmotic minipumps at a dose of 100 micrograms/day/rat. Treatment with RC-160 significantly (P < 0.05) prolonged the mean survival time of rats by 5.3 days as compared to control animals. In both experiments, therapy with RC-160 significantly decreased serum growth hormone or insulin-like growth factor I levels. In the first experiment, receptor assays on R-3327-AT-1 tumor membranes showed high affinity binding sites for somatostatin, bombesin, and epidermal growth factor. At the end of the treatment, receptors for epidermal growth factor were significantly down-regulated by treatment with RC-160 but not with RC-3095. The binding capacity of bombesin receptors was reduced to nondetectable levels after the treatment with RC-3095. In cell cultures, high affinity binding sites for bombesin/GRP were found on intact Dunning R-3327-AT-1 cells, but receptors for somatostatin could not be detected. Proliferation of the AT-1 cell line was significantly inhibited by antagonist RC-3095. However, no effect on tumor cell growth in vitro was observed with analogue RC-160. Our results demonstrate that somatostatin analogue RC-160 and bombesin/GRP antagonist RC-3095 can inhibit the growth of the androgen-independent Dunning R-3327-AT-1 prostatic cancer in rats, although the remission produced by RC-3095 may be of short duration due to a down-regulation of bombesin receptors. Our work suggests the merit of further investigation as to whether these analogues can induce a possible delay in relapse and prolong survival in prostate cancer.
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PMID:Inhibitory effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonist RC-3095 on the growth of the androgen-independent Dunning R-3327-AT-1 rat prostate cancer. 790 3

We investigated the effects of our synthetic bombesin/gastrin-releasing peptide (GRP) antagonists and somatostatin analogue RC-160 on the growth of human small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (non-SCLC) lines in nude mice. Athymic nude mice bearing xenografts of the SCLC NCl-H69 line or non-SCLC NCl-H157 line were treated for 5 and 4 weeks, respectively, with somatostatin analogue RC-160 or various bombesin/GRP antagonists. RC-160, administered s.c. peritumorally at a dose of 100 micrograms per animal per day, inhibited the growth of H69 SCLC xenografts as shown by more than 70% reduction in tumour volumes and weights, as compared with the control group. Bombesin/GRP antagonists, RC-3440, RC-3095 and RC-3950-II, given s.c. peritumorally at a dose of 20 micrograms per animal per day, also inhibited the growth of H69 SCLC tumours. RC-3950-II had the greatest inhibitory effect and decreased tumour volume and weights by more than 80%. The growth of H-157 non-SCLC xenografts was significantly reduced by treatment with RC-160, but not with bombesin/GRP antagonist RC-3095. In mice bearing either tumour model, administration of RC-160 significantly decreased serum growth hormone and gastrin levels. Specific high-affinity receptors for bombesin and somatostatin were found on membranes of SCLC H69 tumours, but not on non-SCLC H157 tumours. Receptor analyses demonstrated high-affinity binding sites for epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on the membranes of H69 and H157 tumours. EGF receptors were down-regulated on H69 tumours after treatment with RC-160 and bombesin/GRP antagonists. The concentration of binding sites for EGF and IGF-I on the H157 tumours was decreased after treatment with RC-160, but bombesin/GRP antagonist RC-3095 had no effect. These results demonstrate that bombesin/GRP antagonists inhibit the growth of H-69 SCLC, but not of H-157 non-SCLC xenografts in nude mice, whereas somatostatin analogue RC-160 is effective in both tumour models. This raises the possibility that these peptide analogues could be used selectively in the treatment of various subclasses of lung cancer.
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PMID:Effects of somatostatin analogue RC-160 and bombesin/gastrin-releasing peptide antagonists on the growth of human small-cell and non-small-cell lung carcinomas in nude mice. 794 94

In the past decade, over 1000 continuous human cell lines have been established from lung cancer biopsy specimens. Numerous growth factors and receptors have been identified in the small cell lung cancer (SCLC) cell lines. SCLC is a neuroendocrine tumor which contains numerous peptides, including bombesin/gastrin releasing peptide (BN/GRP), and receptors. High levels of GRP mRNA and immunoreactivity are present in SCLC cells. The secretion rate of GRP from SCLC cells is increased by vasoactive intestinal peptide (VIP), which elevates the intracellular cAMP. GRP binds to cell surface receptors, elevates cytosolic calcium and stimulates the growth of SCLC cells. Additional SCLC growth factors include insulin-like growth factor I (IGF-I) and transferrin. IGF-I mRNA and protein is present in SCLC. IGF-I binds with high affinity to SCLC cells and stimulates tyrosine kinase activity and growth. Transferrin is also present in SCLC cells. Transferrin binds with high affinity to SCLC cells and stimulates iron transport and growth. Synthetic peptide antagonists and monoclonal antibodies have been identified which disrupt autocrine growth pathways and inhibit SCLC growth.
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PMID:Growth factor and peptide receptors in small cell lung cancer. 838 84

The purpose of these studies was to examine the effects of excess growth hormone (GH) on gastrin and peptide YY (PYY) gene expression. Transgenic mice with the bovine GH gene linked to a mouse metallothionein I promoter were used as a model of chronic GH excess. Antral gastrin mRNA and peptide levels were elevated significantly (P < 0.05) in GH transgenic mice compared with wild type littermates. Ileal PYY mRNA and ileal and colonic PYY levels were significantly elevated in GH transgenic mice compared with wild type littermates. The elevations in gastrin and PYY gene expression in GH transgenic mice were independent of food intake. Serum concentrations of gastrin and PYY were also elevated in GH transgenic mice. Immunohistochemical analysis showed that the density of PYY-containing cells in the colon of GH transgenic mice and wild type littermates did not differ. In addition, the mRNA and protein levels of chromogranin A, a marker of endocrine cells, were not increased in the colon of GH transgenic mice. Together, these data indicate that GH, insulin-like growth factor I, or both can upregulate gastrointestinal gastrin and PYY gene expression directly.
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PMID:Growth hormone upregulates gastrin and peptide YY gene expression. 884 54

The ontogeny of endocrine cells and nerve fibers containing immunoreactivities for 12 regulatory peptides and serotonin was studied in the digestive tract of a flatfish, the turbot (Scophthalmus maximus), using antisera specific for mammalian and teleostean hormones. Transient insulin-immunoreactive (-IR) endocrine cells were detected from day 5 to day 10 in stomach and intestine I. Somatostatin (SOM)-IR cells appeared at day 8 in the stomach anlage and intestine I. In contrast to the islet cells, they reacted with antisera against mammalian (m) SOM-14 and salmon (s) SOM-25. Infrequent nerve fibers reacting only with anti-mSOM-14 appeared around day 24. Thus, different forms of SOM seem to be present in the gastro-entero-pancreatic system and the enteric nervous system. Neuropeptide Y (NPY)-, salmon pancreatic polypeptide (sPP)- and mPP-immunoreactivities coexisted throughout development. In entero-endocrine cells, NPY/PP-immunoreactivity was first observed at day 8 and around day 24 in enteric nerve fibers. Glucagon (GLUC)-IR entero-endocrine cells appeared at day 5. No coexistence of NPY/PP- and GLUC-immunoreactivities was observed. The first insulin-like growth factor I (IGF-I)-IR cells were identified around day 8. They seemed to contain none of the other peptides. Their number and distribution exhibited great interindividual differences. Vasoactive intestinal polypeptide (VIP)-IR entero-endocrine cells appeared as late as around day 24. The first VIP-IR nerve fibers, however, were identified at day 5. Infrequent neurotensin (NT)-IR cells appeared along the intestine around day 10 and NT-IR nerve fibers at day 17. The first serotonin (SER)-IR cells were observed in the stomach anlage around day 10 and SER-IR nerve fibers at day 15 throughout the gastro-intestinal tract. Gastrin (GAS)/cholecystokinin (CCK)-IR cells appeared around day 11 in stomach and intestine I. The first substance P (SP)-IR enteric nerve fibers were detected around day 8 and SP-IR endocrine cells at day 11. Pancreastatin (PST)-IR cells were identified in the stomach anlage and intestine I around day 8 and contained NT-, GAS/CCK- and SER-immunoreactivities in coexistence. Thus, several developmental phases can be distinguished: (1) at the onset of exogenous feeding only transient INS-IR cells and VIP-IR nerve fibers are present; (2) a differentiated entero-endocrine system establishes during the early phase of exogenous feeding; (3) before the final differentiation of stomach and gut GAS/CCK-IR cell appear; (4) after metamorphosis most of the different types of regulatory peptide-containing nerve fibers develop, probably setting up the fine regulation of gastro-intestinal blood flow and motility.
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PMID:An immunohistochemical analysis of the ontogeny, distribution and coexistence of 12 regulatory peptides and serotonin in endocrine cells and nerve fibers of the digestive tract of the turbot, Scophthalmus maximus (Teleostei). 900 19

At birth, the mammalian gastrointestinal tract (GIT) must be able to support a shift from mainly parenteral nutrition in the fetus (via the placenta) to enteral nutrition in the neonate. In the perinatal period the GIT therefore undergoes enhanced growth as well as morphological and functional differentiation, and this maturational programme is influenced by a complex interplay of local, systemic and luminal factors. This review shows how systemic and luminal factors may influence GIT development in the perinatal period of the pig and sheep, two long-gestation species. Adrenocortical hormones play a pivotal role in the prepartum maturation of the GIT in addition to their better known effects on the development of many other tissues and body systems. More particularly, in the fetal pig and sheep, the prenatal development of gastric acid and gastrin secretion, and of GIT hydrolase activities (chymosin, pepsin, amylase, lactase, aminopeptidases) is influenced by cortisol. Additionally, glucocorticoids exert effects throughout the GIT by influencing morphological, cytological, and functional differentiation. Since the GIT epithelial cells comprise a renewing cell population there are also changes in cell kinetics. In addition to systemic factors, the presence of growth factors, hormones and nutrients from swallowed amniotic fluid (fetus) and colostrum (neonate) may influence GIT development. In utero, fetal fluid ingestion has been shown to modulate tissue growth, macromolecule and immunoglobulin transport, enterocyte differentiation, cell turnover and activity of brush-border hydrolases. These effects may be mediated via regulatory peptides (e.g. insulin-like growth factor I, gastrin-releasing peptides, insulin, epidermal growth factor, gastrin). A physiological role of luminally derived growth factors is supported by a number of unique structural and functional adaptations of the GIT in the fetus and neonate (low luminal proteolysis, intestinal macromolecule transport). Thus, in the pig and sheep, both systemic and luminal factors appear to play critical roles in GIT development in the perinatal period.
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PMID:Systemic and luminal influences on the perinatal development of the gut. 935 1