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)

The effects of naloxone, an opiate antagonist, on basal and vagus nerve-induced secretions of GRP, gastrin, and somatostatin were examined using the isolated perfused rat stomach prepared with vagal innervation. Naloxone (10(-6) M) significantly inhibited basal somatostatin secretion in the presence and absence of atropine and of hexamethonium, whereas basal GRP and gastrin secretion was not affected by naloxone. Electrical stimulation (10 Hz, lms duration, 10V) of the distal end of the subdiaphragmatic vagal trunks elicited a significant increase in both GRP and gastrin but a decrease in somatostatin. Naloxone (10(-6) M) failed to affect these responses in the presence or absence of atropine. On the other hand, when hexamethonium was infused, naloxone significantly inhibited both the GRP and gastrin responses to electrical vagal stimulation. Somatostatin secretion was unchanged by vagal stimulation during the infusion of hexamethonium with or without naloxone. These findings suggest that basal somatostatin secretion is under the control of an opiate neuron and that opioid peptides might be involved in vagal regulation of GRP and gastrin secretion.
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PMID:Effects of naloxone on basal and vagus nerve-induced secretions of GRP, gastrin, and somatostatin from the isolated perfused rat stomach. 288 22

The binding of bombesin to its receptors on normal human pancreatic membranes was investigated using high specific activity, radioiodinated bombesin ([125I]-Tyr4-bombesin), prepared by an oxidative method with chloramine-T. Binding was specific, temperature-dependent, saturable, reversible and linearly related to membranes protein concentration. After a 30 min period of incubation with membranes the degradation of the tracer has never been found superior to 20%. Scatchard analysis of binding data was compatible with a single class of binding sites with a high affinity (0.96 nM) and a Bmax of 753 fmol/mg protein. [125I]-Tyr4-bombesin binding to human pancreatic membranes was competitively inhibited by (1-Tyr4-)bombesin, GRP, the nonapeptide of bombesin and litorin but not by unrelated hormones such as somatostatin, CCK, human gastrin, etc. These results describe for the first time the presence of specific receptors for bombesin on human pancreatic membranes. The binding characteristics obtained are comparable with those found in other species.
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PMID:Interaction of [125I]-Tyr4-bombesin with specific receptors on normal human pancreatic membranes. 300 55

The cross-linking agent ethylene glycol-bis(succinimidyl succinate) was used to covalently link 125I-labeled gastrin releasing peptide (125I-GRP) to an Mr 75,000-85,000 surface protein in Swiss 3T3 cells that displays many characteristics of a specific receptor for peptides of the bombesin family. This protein was not present in other cell lines which do not exhibit receptors for bombesin-like peptides. Unlabeled GRP competed for affinity labeling of the Mr 75,000-85,000 protein in a concentration-dependent manner, and other bombesin-related peptides also inhibited the cross-linking of 125I-GRP to this component. In contrast, high concentrations of a variety of other peptide hormones and mitogens had no effect. Affinity labeling of the Mr 75,000-85,000 protein was dependent on the concentration of 125I-GRP and exhibited saturability. 125I-GRP affinity labeling of this protein was also demonstrated by two-dimensional gel electrophoresis. These studies suggest that an Mr 75,000-85,000 surface protein with an isoelectric point of 6.0 to 6.5 is a major component of the receptor for peptides of the bombesin family in Swiss 3T3 cells.
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PMID:Identification of a receptor for peptides of the bombesin family in Swiss 3T3 cells by affinity cross-linking. 303 Oct 56

Infusion of GRP into conscious sheep and dogs produced elevations of systemic plasma levels of insulin, glucagon, and pancreatic polypeptide (PP). In the dog, infusions of GRP produced dose-dependent decreases in plasma glucose levels, whereas, in the sheep, dose-dependent increases in plasma glucose levels occurred. Glucose turnover studies demonstrated that infusions of GRP produce prompt increases in the rate of appearance of glucose in sheep, but previous studies demonstrated a transient decrease in the rate of appearance of glucose in dogs, suggesting that sheep and dogs differ in hepatic responses to the elevated levels of insulin and glucagon. GRP was a potent PP secretagogue in the sheep, whereas, in contrast to results in the dog, infusions of GRP did not result in elevations of plasma levels of gastrin in sheep. GRP has multiple complex stimulatory effects on the endocrine pancreas, and there exist species-dependent differences in responses, which affect the potency and spectrum of the hormone-releasing activity of GRP. Further studies are required to determine the precise anatomical relation of GRP-containing nerve fibers to islet cells and to elucidate the pathways by which GRP activates endocrine pancreatic hormone release.
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PMID:The effect of gastrin-releasing peptide on the endocrine pancreas. 307 Dec 22

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

Molecular and cell biologic studies of a large number of lung cancer cell lines of all histologic types have revealed several mechanisms active in the pathogenesis of these cells. Small cell lung cancer (also called "oat cell" lung cancer) has a deletion involving chromosome region 3p(14-23) that is confirmed by DNA restriction fragment length polymorphisms analysis (studies done in collaboration with Dr. Susan Naylor). Several lung cancers of both small cell and non-small cell type (including adeno- and squamous cell lung cancer) express the proto-oncogenes c-, N-, or L-myc, and in some cases more than one of these family members. N-myc appears restricted in its expression to the small cell lung cancer type while c-myc and L-myc can be expressed in both small cell and non-small cell lung cancers. Many lung cancers of all histologic types also express large amounts of p53, which are not correlated with the amount or type of myc gene product expressed. In small cell lung cancer, high levels of myc gene expression are usually associated with gene amplification, and not uncommonly there is rearrangement of some of the amplified copies. In non-small cell lung cancer, expression without amplification or rearrangement of myc genes is seen. In contrast, high level expression of p53 is not associated with gene amplification in any lung cancer type. In addition, to these proto-oncogenes acting at a presumed nuclear locus, there is increased expression of various ras family members and the c-raf-1 proto-oncogene (in collaboration with Dr. Ulf Rapp). Lung cancer cells in tissue culture can grow in medium without serum and few or no other growth factors added. Thus, it appears that lung cancer cells can produce their own growth factors which can act in an "autocrine" fashion. The best characterized example of this is gastrin releasing peptide (GRP, also called bombesin) produced by small cell lung cancer. In at least some small cell lung cancers, interference with GRP action by specific monoclonal antibodies results in inhibition of tumor cell growth in culture and in nude mouse xenografts. Thus, constitutively expressed GRP gene may function as a cellular oncogene under certain circumstances in small cell lung cancer. Based on these observations we are proposing to test monoclonal anti-GRP antibodies in patients.
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PMID:Chromosomal deletion, gene amplification, alternative processing, and autocrine growth factor production in the pathogenesis of human lung cancer. 333 4

Using radioimmunoassay, reverse phase high pressure liquid chromatography (rp HPLC) and immunohistochemistry, we have identified gastrin releasing peptide-immunoreactivity (GRP-IR) in the rat retina. The concentration of GRP-IR in retinal extracts was 7.4 +/- 0.6 ng/g wet wt. (mean +/- S.E.M. n = 15). There was no significant difference between the levels of immunoreactivity in 12-h light and 12-h dark adapted retinae. rp HPLC analysis of retinal extracts demonstrated that two main immunoreactive components were present which corresponded in retention time to GRP10 (neuromedin C) and GRP14 (GRP14-27). A small amount of material also co-eluted with GRP27. Using immunohistochemistry, the immunoreactivity has been localised in the inner retinal layers. Immunoreactive somata were present in the proximal inner nuclear layer and in the ganglion cell layer. Fibre staining was present in laminae 2 and 4 of the inner plexiform layer. Somatal staining was increased by pretreatment of retinae with vincristine while the laminar staining was markedly reduced. These results demonstrate the existence of GRP-like peptides in the rat retina which has not previously been reported.
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PMID:Gastrin-releasing peptide (GRP) immunoreactivity in the rat retina: a radioimmunoassay, immunohistochemical and chromatographic study. 339 Jun 95

To assess the effects of endogenous GRP on vagal gastrin release and acid secretion, anti-GRP gamma-globulin was infused in anesthetized rats to bind endogenously released GRP. Anti-GRP gamma-globulin blocked the gastrin-releasing effects caused by 4 micrograms/kg/hr of exogenous GRP infusion and suppressed gastrin release by electrical vagal stimulation. In spite of this suppression, anti-GRP gamma-globulin did not alter basal or vagal-stimulated acid secretion.
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PMID:Effects of anti-GRP gamma-globulin on gastrin release and gastric secretion in the rat: evidence for the physiologic role of endogenous GRP in the regulation of gastric function. 362 10

The carboxyl terminal decapeptide of gastrin-releasing peptide (GRP-10), a small, naturally occurring bombesin-like peptide, has been isolated from canine antral muscle, synthesized, and its bioactivity compared with other synthetic and natural gastrin-releasing peptides on stimulation of spontaneously occurring contractions of canine circular antral muscle in vitro. Concentrations of peptides were verified by amino acid analysis and radioimmunoassay. In this system three forms of natural canine GRP, synthetic GRP-10, synthetic porcine gastrin-releasing heptacosapeptide (GRP-27), [Gln3]GRP-10, and [Arg3]GRP-10 all were similar in potency to synthetic amphibian bombesin. These results differ from the low activity of GRP-10 previously reported in rat brain. The full biological potency on canine antral motility and the presence of GRP-10 in nerve fibers in the gut and in the spinal cord suggest a possible role for this peptide as a neurotransmitter or neuromodulator in regulation of smooth muscle contraction.
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PMID:Potency of natural and synthetic canine gastrin-releasing decapeptide on canine antral muscle. 370 25

Neuromedin C, the smaller molecular form of gastrin releasing peptide (GRP [18-27]), has been recently identified from canine intestinal muscle and porcine spinal cord. This study was conducted to determine if this newly identified peptide retains biological activity on canine pancreas in vivo. Intravenous injection of graded doses of synthetic Neuromedin C caused a marked increase of systemic blood pressure and initial reduction of pancreatic blood flow in eleven anesthetized dogs, as measured by Laser Doppler Flowmetry. Flow volume and protein output of pancreatic juice were also increased by Neuromedin C in a dose-related manner in six dogs. These results suggest that this peptide is one of the biologically active forms of mammalian bombesin-like peptides and may possess physiological significance as a novel neuropeptide.
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PMID:Effect of synthetic neuromedin C, a decapeptide of gastrin-releasing peptide (GRP [18-27]), on blood flow and exocrine secretion of the pancreas in dogs. 389 15


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