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)

Physiological responses to mammalian bombesin-like peptides were studied in Xenopus oocytes injected with mRNA isolated from Swiss 3T3 cells and rat esophagus in order to identify and characterize bombesin receptor subtypes. Both groups respond similarly to either gastrin releasing peptide or neuromedin B, but only the response to neuromedin B in oocytes expressing the esophagus mRNA is not blocked by a specific gastrin releasing peptide receptor antagonist, des-Met-[D-Phe6]Bn(6-13) ethyl ester. Complete desensitization of gastrin releasing peptide-evoked responses in oocytes expressing esophagus mRNA does not abolish neuromedin B-evoked responses. A single application of neuromedin B abolishes responses to subsequently applied gastrin releasing peptide in oocytes expressing esophagus, but not Swiss 3T3, mRNA. RNA blot hybridization studies using a Swiss 3T3 gastrin releasing peptide receptor cDNA probe show no detectable hybridization in esophagus mRNA samples. These data suggest that a gastrin releasing peptide receptor is expressed in the esophagus and that it is distinct from that expressed in Swiss 3T3 cells and may represent a third subtype of mammalian bombesin receptor.
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PMID:Distinguishing bombesin receptor subtypes using the oocyte assay. 185 Feb 73

Endocytosis of the gastrin releasing peptide receptor (GRP-R) may regulate cellular responses to GRP. We observed endocytosis in transfected epithelial cells by confocal microscopy using cyanine 3-GRP (cyanine 3.18-labeled gastrin releasing peptide) and GRP-R antibodies. At 4 degrees C, cy3-GRP and GRP-R were confined to the plasma membrane. After 5 min at 37 degrees C, ligand and receptor were internalized into early endosomes with fluorescein isothiocyanate-transferrin. After 10 min, cy3-GRP and GRP-R were in perinuclear vesicles, and at 60 min cy3-GRP was in large, central vesicles, while GRP-R was at the cell surface. We quantified surface GRP-R using an antibody to an extracellular epitope and an 125I-labeled secondary antibody. After exposure to GRP, there was a loss and subsequent recovery of surface GRP-R. Recovery was unaffected by cycloheximide, and thus independent of new protein synthesis, but was attenuated by acidotropic agents, and therefore required endosomal acidification. Internalization of 125I-GRP, assessed using an acid wash, was maximal after 10-20 min, and was clathrin-mediated since it was inhibited by hyperosmolar sucrose and phenylarsine oxide. Thus, GRP and its receptor are rapidly internalized into early endosomes and then dissociate in an acidified compartment. GRP is probably degraded whereas the GRP-R recycles.
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PMID:Direct observation of endocytosis of gastrin releasing peptide and its receptor. 787 31

PURPOSE:Gastrin-releasing peptide (GRP) is a 27-amino acid neuropeptide that has been identified in the cytoplasm of many neuroendocrine tumors. Gastrin releasing peptide has been labeled as an autocrine growth factor in small cell lung carcinomas. Recent work has also shown this to be true in the growth of neuroblastoma cells in vitro. The purpose of this study was to demonstrate GRP and its receptor (GRP-R) in resected human neuroblastomas and to correlate the presence or absence with other known predictors of poor prognosis.To demonstrate the presence of GRP and GRP-R mRNA, total RNA was extracted from human neuroblastoma cells. A reverse transcription-polymerase chain reaction (RT-PCR) was then performed using specific primers. The products of the RT-PCR were then confirmed to be GRP and GRP-R cDNA by Southern blot analysis. The RT-PCR products were then sequenced, and these sequences were compared with the know sequences of GRP and GRP-R DNA.N = 19. GRP and GRP-R mRNA were present in all neuroblastoma specimens. Although no correlation with other known predictors of poor prognosis existed, transcripts of four different sizes (400, 450, 500, and 950 bp) were seen in the GRP-R transcripts. The sequences of the 950 bp-sized transcript reverse transcription PCR products were identical to the known GRP-R.We conclude that gastrin releasing peptide and gastrin releasing peptide receptor mRNA are present in all human neuroblastomas. Although qualitatively it appears to lack prognostic significance, its ubiquitous nature in the tumor suggests it may be a useful target on which to base future treatment modalities.
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PMID:Gastrin-releasing peptide: a potential growth factor expressed in human neuroblastoma tumors(1). 1122 44

The ability of nonpeptide antagonists to interact with gastrin releasing peptide receptors on lung cancer cells was investigated. PD176252 (3-(1H-Indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]-2-methyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide) and PD168368 (3-(1H-Indol-3-yl)-2-methyl-2-[3(4-nitro-phenyl)-ureido]-N-(1-pyridin-2-yl-cyclohexylmethyl)-propionamide) inhibited specific 125I-gastrin releasing peptide binding to NCI-H1299 cells with IC50 values of 20 and 1500 nM, respectively. Similar binding results were obtained using NCI-H157, H345 and N592 human lung cancer cells. PD176252 inhibited the ability of 1 nM bombesin to cause elevation of cytosolic calcium in Fura-2 loaded NCI-H345 or H1299 cells, whereas it had no effect on basal cytosolic calcium. PD176252 antagonized the ability of 10 nM bombesin to cause elevation of c-fos mRNA in NCI-H1299 cells. Also, PD176252 inhibited the ability of 100 nM bombesin to cause tyrosine phosphorylation of focal adhesion kinase in NCI-H1299 cells. Using a [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay, PD176252 was more potent than PD168368 at inhibiting NCI-H1299 proliferation. Also, 1 microM PD176252 significantly inhibited lung cancer colony number in vitro. PD176252 in a dose-dependent manner inhibited NCI-H1299 xenograft growth in nude mice in vivo. These results indicate that PD176252 is a gastrin releasing peptide receptor antagonist, which inhibits the proliferation of lung cancer cells.
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PMID:Nonpeptide gastrin releasing peptide receptor antagonists inhibit the proliferation of lung cancer cells. 1290 92

Panic disorder (PD) is a debilitating anxiety disorder, characterized by recurrent episodes of intense fear that are accompanied by autonomic and psychological symptoms leading to behavioral impairment. Basic research implicates neuropeptide-signaling genes in the modulation of anxiety and stress. The genes encoding corticotropin releasing hormone receptor 1 (CRHR1), tachykinin receptor 1 (TACR1), gastrin releasing peptide (GRP), and gastrin releasing peptide receptor (GRPR) were selected as candidates for PD based on their biology. Linkage and association analysis in 120 multiplex U.S. PD pedigrees was performed using 21 single nucleotide polymorphisms (SNPs). Parametric and non-parametric linkage tests in pedigrees, for single point and multipoint analysis, revealed limited support for genetic linkage to TACR1 (parametric and non-parametric lod scores approximately 1). The family-based association test (FBAT) generated nominal support for allelic association in TACR1 (P = 0.02), and GRP (P = 0.02), findings which must be considered in the light of multiple comparisons. Further exploration of the GRP and TACR1 findings in large case-control PD samples may provide more definitive evidence implicating these loci in the genetic etiology of PD.
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PMID:Association and linkage analysis of candidate genes GRP, GRPR, CRHR1, and TACR1 in panic disorder. 1845 85

The gastrin releasing peptide receptor (GRPR) has been found to be strongly expressed in various types of cancers such as prostate and breast carcinomas. The GRPR ligands gastrin releasing peptide and bombesin can play a very significant role in cancer therapy and diagnostics. In this study we synthesized unlabeled bombesin BBN along with two conjugates in which the correct bombesin (BBN-Rhd) and a mutant bombesin (mBBN-Rhd) sequence was coupled to rhodamine, a fluorescent dye. These novel rhodamine fluorescent conjugates were used to study the targeting and uptake of bombesin on a cellular level. Nine different human cell lines including both tumor and healthy cells were examined using flow cytometry and confocal laser scanning microscopy. GRPR mRNA expression analysis was performed and it was found that the receptor is highly expressed in LNCaP and PC3 cells compared to the rest of other cell lines. Competition experiments were performed to verify the receptor dependence of the labeled conjugates using unmarked bombesin. The present study is a first attempt at direct fluorescence imaging of living cells using bombesin and its target, the GRPR. A rhodamine bombesin conjugate can be used as marker to differentiate between healthy cells and malignant cells such as prostate hyperplasia and prostate carcinoma in the early detection of cancer.
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PMID:Rhodamine-marked bombesin: a novel means for prostate cancer fluorescence imaging. 2372 18

Background: Gastrin-releasing peptide is a member of the bombesin family of peptides. Its cognate receptor, gastrin releasing peptide receptor (GRPR), is widely expressed in cancers of the lung, pancreas and ovaries. Gastrin releasing peptide (GRP) is an autocrine growth factor in small cell lung cancer, which has very poor patient outcomes. High affinity antagonist peptides have been developed for in vivo cancer imaging. In this report we decorated pegylated liposomes with a GRPR antagonist peptide and studied its interaction with, and accumulation within, lung cancer cells. Results: An N-terminally cysteine modified GRPR antagonist (termed cystabn) was synthesised and shown to inhibit cell growth in vitro. Cystabn was used to prepare a targeted 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG2000) lipid conjugate that was formulated into liposomes. The liposomes displayed desirable colloidal properties and good stability under storage conditions. Flow cytometric and microscopic studies showed that fluorescently labelled cystabn-decorated liposomes accumulated more extensively in GRPR over-expressing cells than matched liposomes that contained no cystabn targeting motif. Conclusion: The use of GRPR antagonistic peptides for nanoparticle targeting has potential for enhancing drug accumulation in resistant cancer cells.
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PMID:Bombesin receptor-targeted liposomes for enhanced delivery to lung cancer cells. 3192 34