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)

We have tested the effect of bombesin (BN) and BN-related peptides on the production of interleukin-1 (IL-1) by rat alveolar macrophages. BN incubated with AM alone had no direct effect on IL-1 release. However, at concentrations ranging from 10(-11) M to 10(-6) M, BN significantly enhanced IL-1 release by AM activated with lipopolysaccharide (LPS). A typically U-shaped dose-response relationship was observed with maximal effect obtained between 10(-9) M and 10(-8) M. BN also potentiated the stimulatory effects of other IL-1 inducers including muramyl dipeptide (MDP) and granulocyte-macrophage colony stimulating factor (GM-CSF). The 2- to 3-fold enhancement in IL-1 production seen with BN was blocked by the bombesin receptor antagonist [Leu13,-psi(CH2NH)Leu14]-Bombesin. Furthermore, bombesin-related peptides, gastrin-releasing peptides, (GRP)-27 and GRP-10 also potentiated the stimulatory effects of LPS whereas Neuromedin B (NeB) had no effect. These results suggest that BN-related peptides might play an important role as local modulator(s) of cytokine production and inflammatory reactions in the lung.
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PMID:Bombesin-related peptides modulate interleukin-1 production by alveolar macrophages. 181 4

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

Endocrine cells in the acid-secreting part of the avian stomach, the proventriculus, contain two forms of gastrin-releasing peptide (GRP) of 27 and 6 residues, respectively. We have examined the actions of exogenous GRP-27 and GRP-6 and endogenously released GRP in the control of pancreatic secretion in urethan-anesthetized turkeys. Chicken GRP-27 and the structurally related amphibian peptide bombesin were potent stimulants of fluid and protein output from the pancreas (at 6-100 pmol/kg, iv). GRP-6 had no significant effect at doses up to 1,000 times higher. A bombesin antagonist, (CH3)2-CHCO-[D-Ala24]GRP-20--26-NHCH3, inhibited the action of exogenous chicken GRP-27 but did not inhibit intravenous cholecystokinin octapeptide (CCK-8). Distension of the proventriculus with a solution of peptone produced an increase in the flow of pancreatic juice and an increase in protein output, which was not reduced by atropine. The bombesin antagonist produced a reversible inhibition of this response. A CCK-gastrin antagonist, BOC-beta-Ala-Trp-Leu-Asp-O(CH2)2- phenyl(4F), which inhibited the action of exogenous CCK, had no effect on the pancreatic response to exogenous GRP-27 or to distension of the proventriculus with peptone. We suggest that protein-rich solutions in the proventriculus release GRP, which in turn acts directly on the pancreas to stimulate enzyme secretion.
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PMID:Hormonal control of avian pancreas by gastrin-releasing peptide from the proventriculus. 185 84

Various peptide derivatives of the C-terminal decapeptide of gastrin releasing peptide (GRP-10) and neuromedin B (NMB), i.e., carboxyl terminal fragments, amino terminal fragments and substituted analogues, were chemically synthesized and the structure-activity relationships of the peptides were investigated by comparing their contractile activities on the rat uterus. Peptides with chain lengths of 8 and 9 amino acid residues from the C-terminus of GRP-10 and NMB, respectively, had considerable contractile activities. At position 6 of both decapeptides, Val seems to be more favourable than Thr for inducing contraction of the rat uterus. The substitution of His at position 3 and Leu at position 9 of GRP-10 by Leu and Phe, as in NMB leads to a decrease in activity. Moreover, Trp at position 4 and -Met-NH2 at the C-terminus are essential for activity. Furthermore, in order to characterize the bombesin-receptor profile of rat uterus, the inhibitory effect of two peptide antagonists, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P and [Leu13-phi (CH2NH)-Leu14]-bombesin on the contraction of rat uterus were examined.
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PMID:Structure-activity relationships of mammalian bombesin-like neuropeptides in the contraction of rat uterus. 192 98

Bombesin and structurally related peptides including gastrin releasing peptide (GRP) are potent mitogens for Swiss 3T3 cells. The early cellular and molecular responses elicited by bombesin and structurally related peptides have been elucidated in detail. Further understanding of the molecular basis of the potent mitogenic response initiated by bombesin is required in order to elucidate the mechanism by which the occupied receptor communicates with effector molecules in the cell. Transmembrane signalling mechanisms involving either a tyrosine kinase or a guanine nucleotide-binding regulatory protein (G protein) have been proposed. Here we summarize our experimental evidence indicating that a G protein(s) is involved in the coupling of the bombesin receptor to the generation of intracellular signals related to mitogenesis. Evidence for the role of G proteins in bombesin signal transduction pathways has been obtained by assessing the effects of guanine nucleotide analogues on both receptor-mediated responses in permeabilized cells and ligand binding in membrane preparations. We found that [125I]GRP-receptor complexes were solubilized from Swiss 3T3 cell membranes by using the detergents taurodeoxycholate or deoxycholate. Addition of guanosine 5-[gamma-thio]triphosphate (GTP gamma S) to ligand-receptor complexes isolated by gel filtration enhanced the rate of ligand dissociation in a concentration-dependent and nucleotide-specific manner. These results demonstrate the successful solubilization of [125I]GRP-receptor complexes from Swiss 3T3 cell membranes and provide evidence for the physical association between the ligand-receptor complex and a guanine nucleotide binding protein(s).
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PMID:Mitogenic signalling through the bombesin receptor: role of a guanine nucleotide regulatory protein. 196 86

We studied the effects of a new bombesin/gastrin-releasing peptide (GRP) receptor antagonist, Leu13-psi-(CH2NH)-Leu14-bombesin, on the secretion of gastrin and somatostatin and on the motor activity of isolated perfused porcine antrum in response to infusions of GRP at 10(-10) or 10(-9) mol/l and in response to electric stimulation of the vagus nerves. GRP significantly increased the secretion of gastrin and somatostatin and increased the frequency of antral contractions threefold. At 0.5 x 10(-6) mol/l the antagonist completely abolished the effects on motality and gastrin secretion and strongly inhibited the effect on somatostatin secretion. Vagus stimulation significantly increased gastrin and somatostatin secretion and increased the contraction frequency threefold. The antagonist strongly inhibited the somatostatin response, abolished the motility effects and reversed the stimulatory effect on gastrin secretion to a significant inhibition. Assuming that the antagonist interacts specifically with GRP receptors, we conclude that our data strongly support the concept that GRP-producing nerves are essential for vagally induced secretion of gastrin and somatostatin from the antrum. The GRP nerves may also play a role in the control of gastric motor activity.
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PMID:Identification of the neurotransmitter/neuromodulator functions of the neuropeptide gastrin-releasing peptide in the porcine antrum, using the antagonist (Leu13-psi-CH2 NH-Leu14)-bombesin. 196 86

In the present study we examined the effect of the two endogenous opioids met-enkephalin and met-enkephalin Arg6Phe7 on gastric bombesin-like immunoreactivity, gastrin and somatostatin release. At doses of 10(-11), 10(-9), 10(-8) and 10(-6) M both peptides elicited a significant stimulation of bombesin-like immunoreactivity secretion, while the same doses of morphine were ineffective. The stimulatory effect was abolished by naloxone. Met-enkephalin and met-enkephalin Arg6Phe7 stimulated somatostatin secretion at a dose of 10(-8) M, and this effect was reversible by naloxone. Neither peptide had any effect on gastrin secretion. In conclusion, the data demonstrate that both enkephalins must be considered potential regulators of bombesin-like immunoreactivity secretion in the rat stomach.
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PMID:Effect of met-enkephalin and met-enkephalin-Arg6-Phe7 on bombesin-like immunoreactivity (BLI), somatostatin and gastrin secretion from the perfused rat stomach. 197 Dec 49

Receptor-dependent and -independent regulation of gastrin secretion from cultured human antral G cells was investigated. Human antral mucosal cell preparations that were enriched for G cells were obtained by sequential incubations with collagenase and ethylenediaminetetraacetic acid, centrifugal elutriation, and short-term culture. After a 2-day incubation period, gastrin- and somatostatin-containing cells accounted for 15% and 5%, respectively, of the total adhered-cell population. Forskolin, A23187, and beta-phorbol 12 myristate 13-acetate stimulated basal gastrin secretion from cultured human G cells in a concentration-dependent fashion. These results indicate that gastrin release could be mediated by elevations in cytosolic cyclic adenosine monophosphate levels, calcium influx, or activation of protein kinase C. A direct stimulatory role for bombesin- and gastrin-releasing peptide was supported by experiments showing concentration-dependent enhancement of gastrin release by bombesin from 0.01 fmol/L to 10 nmol/L. The putative bombesin antagonist [Leu13-psi-CH2NH-Leu14] bombesin augmented basal gastrin levels by itself and produced weak inhibition of bombesin-induced gastrin secretion from human antral G cells. Somatostatin potently suppressed forskolin- and bombesin-mediated gastrin release but did not significantly alter basal gastrin levels. These results suggest that bombesin and somatostatin directly activate and inhibit G-cell function via specific and sensitive receptors. Furthermore, the adenylate cyclase and phosphatidyl inositide second messenger systems seem to be intracellular mediators of gastrin secretion from human antral G cells.
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PMID:Gastrin secretion from human antral G cells in culture. 197 10

Tumor cells of a human medullary thyroid carcinoma were isolated and propagated in tissue culture. Several cell lines with different morphology developed from the primary culture, among others a fibroblast-like growing cell line (MTC-F) and a cell line growing as a suspension of single cells and spherical cell clusters (MTC-SK). The MTC-SK cell line was serially propagated for 90 passages, over 3 years. When examined at different times throughout the in vitro period, MTC-SK exhibited properties characteristic of medullary thyroid carcinomas: the cells maintained their epithelioid morphology; endocrine granules were demonstrated in the cytoplasm by electron microscopy; in situ hybridization confirmed the production of calcitonin- and bombesin-mRNA (gastrin releasing peptide); the cells revealed positive immunoreactivity with antibodies to calcitonin, calcitonin gene-related peptide, and bombesin. The in vitro properties of the MTC-SK cells corresponded to the results obtained from the tissue of origin. Cytogenetic studies of the MTC-F cell line revealed a supernumerary metacentric chromosome (20?). In the MTC-SK cell line the predominant findings were terminal chromosomal rearrangements most frequently concerning chromosome 11p, i.e., the locus of the calcitonin and calcitonin gene-related peptide genes and the H-ras oncogene, and a characteristic instability of the centromeric region of chromosome 16 and somatic pairing of the homologous chromosomes 16.
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PMID:Establishment and characterization of continuous cell line MTC-SK derived from a human medullary thyroid carcinoma. 197 48

Dispersed canine antral mucosal cells were prepared by sequential steps of collagenase digestion and EDTA treatment. Cell preparations enriched in gastrin cells were made by centrifugal elutriation followed by step density gradient centrifugation. Specific, saturable, and reversible binding of 125I-[Tyr4]-bombesin was found in all preparations. This saturable binding was time, temperature, and cell number dependent. In both velocity (elutriator) and density cell separation experiments, saturable binding of bombesin correlated with the distribution of cells containing gastrin- but not somatostatin-like immunoreactivity. Maximal specific binding to gastrin (G) cell-enriched fractions was reached in 45 min at 37 degrees C and constituted 90% of total binding. Addition of 100 nM nonradioactive bombesin to cells incubated with 50 pM 125I-[Tyr4]-bombesin for 45 min resulted in time-dependent dissociation of specifically bound tracer to about 40% of the maximal equilibrium binding. Analysis of saturable equilibrium binding yielded a best fit to a one-site model of high affinity binding sites with an apparent Kd of 85 +/- 14 pM and a Bmax of 231,000 +/- 71,000 receptors/gastrin cell. Nonradioactive [Tyr4]-bombesin and related analogs inhibited the specific binding of the tracer in a dose-related manner. The rank order of potency, determined at the IC50, of [Tyr4]-bombesin and related analogs for inhibition of specific binding was bombesin greater than [Tyr4]-bombesin = hGRP-27 greater than GRP-10 greater than ranatensin much greater than neuromedin B. Cholecystokinin, somatostatin, substance K, and kassinin each tested at a concentration of 1 microM did not inhibit bombesin binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of bombesin receptors on canine antral gastrin cells. 197 73


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