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)

Using antisera directed towards the C-terminal region of gastrin releasing peptide (GRP), significant quantities of GRP-like immunoreactivity (GRPLI) were detected in ovine amniotic fluid and in the fetal and maternal circulations. The highest GRPLI levels were found in amniotic fluid (2135 +/- 829 fmol/ml, n = 12; mean +/- SEM), followed by those in ovine fetal (604 +/- 267 fmol/ml, n = 13) and maternal plasma (229 +/- 89 fmol/ml, n = 13). On gel filtration chromatography, the predominant GRPLI form in each fluid eluted in an identical position consistent with the entity being of apparently larger molecular size than porcine GRP1-27. Certain fetal plasma samples contained a second GRPLI peak eluting at the void volume. Hence, during ovine pregnancy a GRPLI entity circulates in fetal and maternal plasma; the entity is of apparently larger molecular size than GRP1-27 but contains a structure immunologically indistinguishable from the bioactive c-terminal region of GRP1-27. Given the recognized bioactivities of GRP, this entity may be an important hormone during ovine fetal life.
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PMID:Gastrin releasing peptide immunoreactivity is present in ovine amniotic fluid and fetal and maternal circulations. MRC Group in Fetal and Neonatal Health and Development. 139 47

Gastrin-releasing polypeptide (GRP) has been implicated in the development of the human fetal lung. To determine whether GRP has a wider role in fetal development, its actions on DNA synthesis and cell replication by isolated epiphyseal growth plate chondrocytes obtained from ovine fetuses between 35 days gestation and near term (145 days) were examined. Chondrocytes were isolated using collagenase from the proximal tibia and cultured in monolayer. Synthesis of DNA was assessed from the incorporation of [3H]thymidine into previously growth-restricted cells after incubation in medium supplemented with GRP1-27 (40-1280 nM). Increase in cell number was assessed after incubation with test medium for 1 week. GRP caused a dose-dependent increase in both cell number and DNA synthetic rate compared to control incubations. Cell number was increased by 50% in the presence of a maximally effective 160 nM GRP and DNA synthesis by up to 800% utilizing chondrocytes obtained from animals of 75-80 days gestation. The mean (+/- SEM) half-maximal concentration of GRP for the stimulation of DNA synthesis was 97 +/- 12 nM (5 separate fetuses). Concentrations of GRP in excess of 160 nM caused a sharp reduction in both cell replication and DNA synthesis. To determine where within the cell cycle GRP exerted its mitogenic action, synchronized chondrocytes were transiently exposed to fetal bovine serum and cultured with GRP for increasing periods of time before pulse labeling with [3H]thymidine during S phase. GRP was as effective in stimulating DNA synthesis when present for the initial 4 h of G1 as when present for the entire G1 period. Since isolated fetal growth plate chondrocytes release insulin-like growth factor II (IGF II) and basic fibroblast growth factor (basic FGF) the possible mediation of GRP action by the release of these peptides or synergistic interactions were examined. Specific antibodies shown to negate the mitogenic actions of exogenous IGFs or basic FGF on chondrocytes did not alter GRP-stimulated DNA synthesis. The release of radioimmunoassayable IGF II by chondrocytes was not altered in the presence of GRP. Coincubation of GRP with submaximal concentrations of IGF I or basic FGF showed additive effects on DNA synthesis. When the actions of galanin were examined it was found to inhibit basal DNA synthesis by chondrocytes at a concentration of 167 nM. However, 66 nM or greater galanin was able to render 160 nM GRP inactive as a mitogen. These results suggest that GRP may potentially influence skeletal development in the ovine fetus and may interact with locally released peptide growth factors or other neuropeptides.
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PMID:Mitogenic action of gastrin-releasing polypeptide on isolated epiphyseal growth plate chondrocytes from the ovine fetus. 157 94

In the present study the effects of gastrin-releasing peptide (GRP1-27), its C-terminal decapeptide neuromedin-C (GRP18-27) and the related peptide neuromedin-B were examined on the secretion of gastrin and somatostatin-like immunoreactivity (SLI) from the isolated perfused rat stomach at intraluminal pH 7 or pH 2. GRP1-27 and GRP18-27 stimulated gastrin secretion equally effective at concentrations of 10(-10), 10(-9), 10(-8), 10(-7) and 10(6)M at luminal pH 7. In addition neuromedin-B was tested at 10(-11), 10(-10), 10(-8) and 10(-6)M and it increased gastrin release similar to equimolar doses of GRP18-27. At luminal pH 2 GRP1-27 stimulated gastrin secretion at 10(-9), 10(-8), 10(-7) and 10(-6)M while GRP18-27 was only effective at 10(-8) and 10(-7)M. Neuromedin-B elicited a gastrin increase at 10(-8)M similar to GRP18-27 and also at 10(-6)M. All three peptides had no significant effect on SLI release at luminal pH 7. At luminal pH 2 GRP1-27 at 10(-9)M and 10(-6)M and GRP18-27 and neuromedin-B at 10(-10)M elicited a significant stimulation of SLI secretion. These data demonstrate that all three bombesin-like peptides GRP1-27, GRP18-27 and neuromedin-B can stimulate gastrin release at either a neutral or an acidic luminal pH, while SLI release is affected only at an acidic intragastric milieu. This suggests that all three forms of bombesin-like peptides are good candidates for the peptidergic regulation of gastrin release in the rat stomach, while their role in somatostatin release seems to be more restricted.
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PMID:Effect of gastrin-releasing peptide (GRP1-27), neuromedin-C (GRP18-27), and neuromedin-B on gastrin and somatostatin secretion from the rat stomach. 257 79

The ability of bombesin (BN)-like peptides to stimulate phosphatidylinositol turnover in rat brain slices was investigated. BN (1 microM) significantly stimulated inositol-1-phosphate (IP1) but not inositol-4,5-biphosphate (IP2) or inositol-1,4,5-trisphosphate (IP3) production using frontal cortex slices in the presence of LiCl (7.5 mM); BN had no effect on cAMP or cGMP levels. BN and the structurally-related gastrin releasing peptide (GRP) elevated IP1 levels in a dose-dependent manner. Similarly, nanomolar concentrations of the GRP fragment (Ac-GRP20-27) significantly elevated IP1 levels, whereas micromolar concentrations of the inactive GRP1-16 did not. BN significantly elevated IP1 levels in those brain regions enriched in BN receptors such as the olfactory bulb, hippocampus, striatum, thalamus and frontal cortex, whereas IP1 levels were not significantly increased in areas which have a low density of BN receptors such as the cerebellum, medulla/pons and midbrain. These data suggest that CNS BN receptors may utilize phosphatidylinositol as a second messenger.
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PMID:Bombesin-like peptides stimulate phosphatidylinositol turnover in rat brain slices. 285 27

Two canine gastrin-releasing peptides originally isolated from gut tissue extracts have been synthesized by solid phase methodology and purified by preparative reverse phase high performance liquid chromatography (RP-HPLC). The synthetic gastrin-releasing peptides GRP1-27 and GRP 5-27 were characterized with regard to homogeneity and composition using nine different RP-HPLC systems, mass spectroscopy, amino acid analysis, Edman degradation, methionine oxidation, and peptide mapping with tryptic, Staph. aureus V8 protease and cyanogen bromide cleavage (the latter two systems performed only with GRP 1-27). Although a scarcity of the natural products prevented quantitative biological comparison of the synthetic and natural peptides, they were found to elute identically on RP-HPLC co-chromatography and similar dose dependent biological potencies were observed in canine antral muscle tissue contraction experiments. Indeed, all the peptides containing the bombesin-like carboxyl terminal decapeptide sequence studied to date have similar biological activities.
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PMID:Solid phase synthesis and characterization of two canine gut gastrin-releasing peptides. 322 Jun 60

Bombesin/gastrin releasing peptide (BN/GRP) receptors were solubilized and purified from human glioblastoma (U-118) and lung carcinoid cell lines (NCI-H720). The U-118 cells, when extracted with CHAPS/cholesterol hemisuccinate (CHS), bound (125I-Tyr4)BN with high affinity (Kd = 2 nM) to a single class of sites (Bmax = 150 fmol/mg protein). Specific (125I-Tyr4)BN binding was inhibited with high affinity by BN, GRP, GRP14-27, and receptor antagonists such as (D-Phe6)BN6-13methylester(ME) and (D-Phe6)BN6-13 propylamide(PA) (IC50 = 2, 22, 3, 1 and 2 nM, respectively) but not GRP1-16 or BN1-12. The solubilized and cellular receptor bound peptides with similar affinity. The solubilized receptor was purified using (Lys0, Gly1-4, D-Ala5)BN and (Lys3, Gly4,5, D-Tyr6)BN3-13 PA affinity resins. When eluted from the affinity resins by NaCl, the receptor bound (125I-D-Tyr6)BN6-13ME with high affinity. The NCI-H720 BN/GRP receptor was purified 86,000-fold after extraction with CHAPS/CHS and purification using both affinity resins. SDS-PAGE analysis indicated that major 65 and 115 kDa proteins were purified. These data indicate that BN/GRP receptors can be solubilized from human cells and purified using affinity chromatography techniques with retention of ligand binding activity.
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PMID:Solubilization and purification of bombesin/gastrin releasing peptide receptors from human cell lines. 839 Dec 95

The suprachiasmatic nuclei (SCN) of the rodent hypothalamus function as a light entrainable circadian pacemaker. The SCN contain moderate to high concentrations of a number of neuropeptides including peptides showing structural homology with the amphibian derived tetradecapeptide, bombesin (BN), called bombesin-like peptides (BNLPs). BNLPs include the 27 amino acid peptide, gastrin releasing peptide (GRP1-27), a smaller decapeptide (GRP18-27) and another decapeptide with less structural homology, neuromedin B (NmB). Immunoreactivity for BN and receptors for BNLPs have been demonstrated in the region of the rat SCN receiving photic input. We studied the effects of local pressure ejections of BNLPs dissolved in saline/1% bovine serum albumin (BSA) vehicle on the extracellularly recorded firing rates of Syrian hamster SCM neurons in a hypothalamic slice preparation. In one study, an ejecting electrode containing BN (10(-8) to 10(-4) M) was positioned 20 to 60 microm from a recording electrode. Of 74 cells tested with BN, 50 (67.6%) showed significant increases in firing rate, while 3 of 29 cells (15.8%) tested with vehicle ejections were activated. In a second study, a single electrode was used for both recordings and pressure ejections. Of 48 cells tested, BN (10(-6) to 10(-4) M) activated 30 (62.5%) and suppressed firing in 4 (8.3%). Of 208 cells tested with GRP1-27 (10(-9) to 10(-4) M), 105 (50.5%) were activated and 2 (1.0%) were suppressed. The percentage of cells responding increased with the concentration of GRP1027 used in the electrode. No circadian variation in responsiveness to GRP1-27 was detected. GRP18-27 (5 x 10(-5) to 10(-4) M) activated 10 out of 18 cells tested (55.6%), while NmB (10(-4) M) activated 2 out of 30 cells tested (6.7%) and vehicle ejections activated 1 out of 36 cells tested (2.8%). GRP1-27, GRP18-27 and BN, the BNLPs showing the greatest degree of structural homology, activate approximately 50% of SCN cells, apparently via the BN/GRP-preferring receptor subtype, and may play a role in photic entrainment.
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PMID:Electrophysiological effects of pressure-ejected bombesin-like peptides on hamster suprachiasmatic nucleus neurons in vitro. 868 Apr 27

The effects of bombesin (BB) on mitogen activated protein (MAP) kinase were investigated using non-small cell lung cancer (NSCLC) cells. By Western blot, both 42 and 44 kDalton forms of MAP kinase were present in NCI-H1299 and NCI-H838 cells. Addition of BB to NCI-H1299 cells resulted in phosphorylation of the MAP kinase substrate myelin basic protein (MBP). Phosphorylation of MBP was maximal 6 min after the addition of 10 nM BB to NCI-H1299 cells. Addition of gastrin releasing peptide (GRP) or GRP14-27 but not GRP1-16 to NCI-H 1299 cells caused MBP phosphorylation. The effects of BB were inhibited by BW2258U89, a BB receptor antagonist, and PD98059, a MAP kinase kinase inhibitor. Also, PD98059 inhibited the clonal growth of NCI-H1299 cells. These data suggest that MAP kinase may be an important regulatory enzyme in NSCLC.
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PMID:Bombesin activates MAP kinase in non-small cell lung cancer cells. 1009 32

Serum gastrin is known to be elevated in patients with liver-metastasizing colon cancer; thus, cholecystokinin (CCK) B/gastrin receptors may also be up-regulated. A liver-invasive model of colon cancer was established with the human colonic cell line C170HM2, which expresses the CCKB/gastrin receptor at both the gene and protein level. An antiserum has been derived that is directed against the NH2-terminal 17 amino acids of the human CCKB/gastrin receptor coupled to diphtheria toxoid. The peptide was denoted gastrin receptor protein (GRP) 1. The therapeutic effect of GRP1 antiserum was evaluated on the liver invasion of C170HM2 tumors. Biodistribution studies revealed that GRP1 antiserum localized preferentially within the liver tumors when compared with normal liver tissue (1.5-fold increase after 24 h; P < 0.05). Antiserum against GRP1 inhibited both tumor take rate and final liver tumor weight when compared with treatment with control serum in mice with an increasing tumor burden. Liver tumor weights were reduced from 0.37 to 0.10 gram (P = 0.0155), 1.25 grams to 0.76 gram (P = 0.003) and 1.89 grams to 0.76 gram (P = 0.0068, all Mann-Whitney nonparametric U test). Necrosis and apoptosis were increased in the GRP1 antiserum-treated tumors when compared with control serum-treated tumors. As shown by Western blotting, CCKB/gastrin receptor expression of C170HM2 xenografts after treatment with GRP1 antiserum shifted to a predominantly lower molecular weight form (Mr 45,000) that is known to be an internalized form of the receptor. In conclusion, targeting of the CCKB/gastrin receptor may yield a valuable therapeutic modality for the treatment of advanced colon cancer.
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PMID:Antiserum raised against an epitope of the cholecystokinin B/gastrin receptor inhibits hepatic invasion of a human colon tumor. 1105 89