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Etsuko Wada - One of the best experts on this subject based on the ideXlab platform.

  • Neuromedin B and Gastrin-Releasing Peptide mRNAs Are Differentially Distributed in the Rat Nervous System
    2013
    Co-Authors: Etsuko Wada, James Way, Anne Marie Lebacq-verheyden, James F. Batteyl
    Abstract:

    The Bombesin-Like Peptides are a family of structurally related amidated peptide ligands that are known to have a variety of potent pharmacological actions on various cells, including neurons in the rat brain. Two mammalian representatives of the bombesin family of Peptides have been identified, gastrin-releasing peptide (GRP) and neuromedin B (NMB). Previously, we cloned the rat preproGRP gene and determined the locations of neurons expressing this gene using in situ hybridization. In this study, we describe the structure and sequence of the rat preproNMB gene, and the first detailed cellular localization of preproNMB mRNA in rat brain using in situ hybridization. Nucleotide sequence analysis of cDNA and genomic clones reveals a 117 amino acid precursor whose overall structure is similar to that described for human preproNMB. Sequence similarity between the ra

  • Bombesin-Like Peptides and mast cell responses: relevance to bronchopulmonary dysplasia?
    American journal of respiratory and critical care medicine, 2003
    Co-Authors: Meera Subramaniam, Etsuko Wada, David H. Coy, York E. Miller, Kumiya Sugiyama, Yanping Kong, Peter F. Weller, Keiji Wada, Mary E. Sunday
    Abstract:

    Bombesin-Like Peptides (BLPs) are elevated in newborns who later develop bronchopulmonary dysplasia (BPD). In baboon models, anti-BLP blocking antibodies abrogate BPD. We now demonstrate hyperplasia of both neuroendocrine cells and mast cells in lungs of baboons with BPD, compared with non-BPD controls or BLP antibody-treated BPD baboons. To determine whether BLPs are proinflammatory, bombesin was administered intratracheally to mice. Forty-eight hours later, we observed increased numbers of lung mast cells. We analyzed murine mast cells for BLP receptor gene expression, and identified mRNAs encoding bombesin receptor subtype 3 and neuromedin-B receptor (NMB-R), but not gastrin-releasing peptide receptor. Only NMB-R-null mice accumulated fewer lung mast cells after bombesin treatment. Bombesin, gastrin-releasing peptide, NMB, and a bombesin receptor subtype 3-specific ligand induced mast cell proliferation and chemotaxis in vitro. These observations support a role for multiple BLPs in promoting mast cell responses, suggesting a mechanistic link between BLPs and chronic inflammatory lung diseases.

  • Bombesin and its family of Peptides: prospects for the treatment of obesity.
    European journal of pharmacology, 2002
    Co-Authors: Kazuyuki Yamada, Etsuko Wada, Yuko Santo-yamada, Keiji Wada
    Abstract:

    Bombesin, its family of Bombesin-Like Peptides, and many other Peptides/hormones modulate biological and behavioral functions in animals. Among the wide variety of functions influenced by bombesin/Bombesin-Like Peptides, the most prominent may be their role in feeding-related behavior. Over many years, intensive psychopharmacological studies have addressed the mechanisms by which these Peptides induce feeding suppression, and the results suggest the applicability of bombesin/Bombesin-Like Peptides for the treatment of eating disorders and/or obesity in humans. Recent studies using gene-knockout mice also shed new light on the relationship between bombesin/Bombesin-Like Peptides and feeding behavior. In addition, genetic analyses of the possible links between bombesin/Bombesin-Like Peptides/receptors and human obesity have also been undertaken. Here, we briefly review the literature pertaining to the relationship between bombesin/Bombesin-Like Peptides and feeding behavior-with particular attention to human subjects-and discuss the pharmacotherapeutic potential of bombesin/Bombesin-Like Peptides with regard to obesity.

  • Neuromedin-B receptor transfected BALB/3T3 cells: signal transduction and effects of ectopic receptor expression on cell growth
    Regulatory peptides, 1993
    Co-Authors: David Dobrzanski, Etsuko Wada, James F. Battey, Yoav Sharoni, Edward A. Sausville
    Abstract:

    Bombesin-Like Peptides including neuromedin B have been proposed as autocrine or paracrine growth factors for carcinomas. To examine signal transduction and regulation of cell growth by NMB, transfectants were created with the rat NMB receptor (NMB-R) gene in BALB/3T3 cells which do not express an endogenous bombesin peptide receptor. The resultant cell line, NMB-8, expresses 800,000 NMB binding sites/cell. Addition of NMB has a biphasic effect on [3H]thymidine ([3H]dT) incorporation in confluent and quiescent cells: up to 10 nM of NMB causes a 1.5-3-fold stimulation of [3H]dT incorporation, but at greater than 10 nM there is inhibition of [3H]dT incorporation, and at 100 nM of NMB there is inhibition of cell growth. NMB causes protracted increases in intracellular Ca2+, and pertussis toxin (PT)-insensitive phosphatidylinositol (PI) turnover. NMB-mediated increase in membrane phospholipase-C activity is stimulated by guanosine 5'-O-(3-thiotriphosphate). Arachidonate release is also activated by NMB in a PT-insensitive manner. Brief exposure to 12-tetradecanoylphorbol 13-acetate inhibits NMB-mediated PI turnover but not arachidonate release. Thus, in NMB-8 cells, distinct mechanisms govern NMB-mediated phospholipase-C activation and arachidonate release. Also, neuromedin-B is potentially a bifunctional regulator of cell growth.

  • neuromedin b receptor transfected balb 3t3 cells signal transduction and effects of ectopic receptor expression on cell growth
    Regulatory Peptides, 1993
    Co-Authors: David Dobrzanski, Etsuko Wada, James F. Battey, Yoav Sharoni, Edward A. Sausville
    Abstract:

    Bombesin-Like Peptides including neuromedin B have been proposed as autocrine or paracrine growth factors for carcinomas. To examine signal transduction and regulation of cell growth by NMB, transfectants were created with the rat NMB receptor (NMB-R) gene in BALB/3T3 cells which do not express an endogenous bombesin peptide receptor. The resultant cell line, NMB-8, expresses 800,000 NMB binding sites/cell. Addition of NMB has a biphasic effect on [3H]thymidine ([3H]dT) incorporation in confluent and quiescent cells: up to 10 nM of NMB causes a 1.5-3-fold stimulation of [3H]dT incorporation, but at greater than 10 nM there is inhibition of [3H]dT incorporation, and at 100 nM of NMB there is inhibition of cell growth. NMB causes protracted increases in intracellular Ca2+, and pertussis toxin (PT)-insensitive phosphatidylinositol (PI) turnover. NMB-mediated increase in membrane phospholipase-C activity is stimulated by guanosine 5'-O-(3-thiotriphosphate). Arachidonate release is also activated by NMB in a PT-insensitive manner. Brief exposure to 12-tetradecanoylphorbol 13-acetate inhibits NMB-mediated PI turnover but not arachidonate release. Thus, in NMB-8 cells, distinct mechanisms govern NMB-mediated phospholipase-C activation and arachidonate release. Also, neuromedin-B is potentially a bifunctional regulator of cell growth.

James F. Battey - One of the best experts on this subject based on the ideXlab platform.

  • Correlation of expression of Bombesin-Like Peptides and receptors with growth inhibition by an anti-bombesin antibody in small-cell lung cancer cell lines.
    Lung cancer (Amsterdam Netherlands), 1998
    Co-Authors: Han-kwang Yang, James F. Battey, Frank Scott, Jane B. Trepel, Bruce E. Johnson, Michael J. Kelley
    Abstract:

    Abstract The murine anti-bombesin monoclonal antibody, 2A11, has been demonstrated to inhibit growth of some small-cell lung cancer (SCLC) cells in nude mice xenografts and in a clinical trial. To determine if the expression of Bombesin-Like Peptides (BLP) and their receptors (GRP-R and NMB-R) correlate with an in vitro response to 2A11, we measured these parameters in seven SCLC cell lines. Gastrin releasing peptide (GRP) mRNA was detected in three of seven cell lines (NCI-H69, NCI-H345, NCI-H510) and neuromedin B (NMB) mRNA was detected in all seven lines using an RNase protection assay (RPA). Immunoreactive BLP was detected in the cell pellets of all lines (range 0.11–59.90 pmol/mg protein) by a solid phase GRP radioimmunoassay (RIA) using 125 I-labeled 2A11. RPA detected GRP-receptor mRNA in two cell lines (NCI-H69 and NCI-H345) and NMB-receptor in three lines (NCI-H345, NCI-H510, and NCI-H660). Reverse transcriptase–PCR confirmed the presence of receptor mRNA in these lines and detected NMB-receptor in an additional three lines (NCI-H69, NCI-H82, and NCI-H187). Calcium mobilization in response to BLP stimulation was detected in the six cell lines expressing either GRP-R or NMB-R mRNA but not in NCI-N417, which had no detectable BLP-receptor. 2A11 (5 μ g/ml) inhibited colony formation by 26–61% after 2 weeks in all cell lines except NCI-N417. Thus, growth inhibition by 2A11 requires the presence of at least one BLP-receptor. These findings may be useful in selecting patients with SCLC for treatment with 2A11.

  • Neuromedin-B receptor transfected BALB/3T3 cells: signal transduction and effects of ectopic receptor expression on cell growth
    Regulatory peptides, 1993
    Co-Authors: David Dobrzanski, Etsuko Wada, James F. Battey, Yoav Sharoni, Edward A. Sausville
    Abstract:

    Bombesin-Like Peptides including neuromedin B have been proposed as autocrine or paracrine growth factors for carcinomas. To examine signal transduction and regulation of cell growth by NMB, transfectants were created with the rat NMB receptor (NMB-R) gene in BALB/3T3 cells which do not express an endogenous bombesin peptide receptor. The resultant cell line, NMB-8, expresses 800,000 NMB binding sites/cell. Addition of NMB has a biphasic effect on [3H]thymidine ([3H]dT) incorporation in confluent and quiescent cells: up to 10 nM of NMB causes a 1.5-3-fold stimulation of [3H]dT incorporation, but at greater than 10 nM there is inhibition of [3H]dT incorporation, and at 100 nM of NMB there is inhibition of cell growth. NMB causes protracted increases in intracellular Ca2+, and pertussis toxin (PT)-insensitive phosphatidylinositol (PI) turnover. NMB-mediated increase in membrane phospholipase-C activity is stimulated by guanosine 5'-O-(3-thiotriphosphate). Arachidonate release is also activated by NMB in a PT-insensitive manner. Brief exposure to 12-tetradecanoylphorbol 13-acetate inhibits NMB-mediated PI turnover but not arachidonate release. Thus, in NMB-8 cells, distinct mechanisms govern NMB-mediated phospholipase-C activation and arachidonate release. Also, neuromedin-B is potentially a bifunctional regulator of cell growth.

  • neuromedin b receptor transfected balb 3t3 cells signal transduction and effects of ectopic receptor expression on cell growth
    Regulatory Peptides, 1993
    Co-Authors: David Dobrzanski, Etsuko Wada, James F. Battey, Yoav Sharoni, Edward A. Sausville
    Abstract:

    Bombesin-Like Peptides including neuromedin B have been proposed as autocrine or paracrine growth factors for carcinomas. To examine signal transduction and regulation of cell growth by NMB, transfectants were created with the rat NMB receptor (NMB-R) gene in BALB/3T3 cells which do not express an endogenous bombesin peptide receptor. The resultant cell line, NMB-8, expresses 800,000 NMB binding sites/cell. Addition of NMB has a biphasic effect on [3H]thymidine ([3H]dT) incorporation in confluent and quiescent cells: up to 10 nM of NMB causes a 1.5-3-fold stimulation of [3H]dT incorporation, but at greater than 10 nM there is inhibition of [3H]dT incorporation, and at 100 nM of NMB there is inhibition of cell growth. NMB causes protracted increases in intracellular Ca2+, and pertussis toxin (PT)-insensitive phosphatidylinositol (PI) turnover. NMB-mediated increase in membrane phospholipase-C activity is stimulated by guanosine 5'-O-(3-thiotriphosphate). Arachidonate release is also activated by NMB in a PT-insensitive manner. Brief exposure to 12-tetradecanoylphorbol 13-acetate inhibits NMB-mediated PI turnover but not arachidonate release. Thus, in NMB-8 cells, distinct mechanisms govern NMB-mediated phospholipase-C activation and arachidonate release. Also, neuromedin-B is potentially a bifunctional regulator of cell growth.

  • Molecular genetic analysis of two distinct receptors for mammalian Bombesin-Like Peptides.
    Journal of the National Cancer Institute. Monographs, 1992
    Co-Authors: James F. Battey, Hagit Shapira, E Wada, M Corjay, J Way, Z Fathi, Richard N. Harkins, Timothy Slattery, E Mann
    Abstract:

    The mammalian Bombesin-Like Peptides are known to be growth factors for certain cells with high-affinity bombesin receptors and have been implicated as autocrine growth factors influencing the pathogenesis and progression of a subset of human small-cell lung carcinomas. Thus, antagonists that interfere with bombesin receptor-ligand interaction might prove to be of value in treatment of gastrin-releasing peptide (GRP)-responsive tumors. A precise definition of the structure and properties of the bombesin receptors found on human lung cancer cells would provide important information for the design and rational application of such antagonists. Recently, we isolated cDNA clones encoding two distinct receptors for the mammalian Bombesin-Like Peptides, GRP, and neuromedian B (NMB). The two receptors show 56% amino acid identity, encode seven putative transmembrane domains, and are members of the G-protein-coupled receptor superfamily. Ligand-binding studies show that while both receptors can be activated by either GRP or NMB, one receptor has a higher affinity for GRP than for NMB (GRP-R), while the other has a higher affinity for NMB than for GRP (NMB-R). A different spectrum of antagonists is needed to block responses from the two different receptors. These studies indicate that it will be critical in future studies to define which bombesin receptor subtypes are present on a given tumor to optimize the potential therapeutic benefit of antagonists in blocking growth.

  • cDNA cloning, characterization, and brain region-specific expression of a neuromedin-B-preferring bombesin receptor
    Neuron, 1991
    Co-Authors: Etsuko Wada, David H. Coy, Robert T. Jensen, Hagit Shapira, James Way, Kiyoshi Kusano, Anne Marie Lebacq-verheyden, James F. Battey
    Abstract:

    Recent binding studies in the central nervous system and other tissues provide evidence that the mammalian Bombesin-Like Peptides, gastrin-releasing peptide (GRP) and neuromedin-B (NMB), exert their numerous physiological effects through at least two different receptors. We describe the structure and expression of a cloned NMB-preferring bombesin receptor (NMB-R) with properties distinct from a GRP-preferring bombesin receptor (GRP-R) reported previously. In particular, the NMB-R shows higher affinity binding to NMB than to GRP in BALB 3T3 fibroblasts expressing the cloned NMB-R. The distinct regional distribution of NMB-R and GRP-R mRNA in the brain suggests that both bombesin receptor subtypes play independent roles in mediating many of the dramatic effects of Bombesin-Like Peptides in the central nervous system.

Benjamin Rusak - One of the best experts on this subject based on the ideXlab platform.

  • Effects of ionophoretically applied Bombesin-Like Peptides on hamster suprachiasmatic nucleus neurons in vitro.
    European Journal of Pharmacology, 1994
    Co-Authors: Hugh D. Piggins, David J Cutler, Benjamin Rusak
    Abstract:

    Abstract Ionophoresis of the smaller Bombesin-Like Peptides (gastrin releasing peptide [GRP]-(18–27), neuromedin B, and bombesin) evoked responses from 30–60% of hamster suprachiasmatic nucleus cells recorded in a hypothalamic slice preparation, depending on the circadian phase. We also demonstrated for the first time that the putative Bombesin-Like peptide receptor antagonists [ D -F5, D -Phe6, D -Ala11]bombesin-(6–13)methyl ester (BIM 26226) and [ D -Phe6,Des-Met14]bombesin- (6–14)ethyl amide can be applied ionophoretically to block physiological responses to Bombesin-Like Peptides. Together with earlier findings, these results show that Bombesin-Like Peptides administered by several methods can potently alter the firing rates of hamster suprachiasmatic nucleus neurons in vitro. These results indicate that Bombesin-Like Peptides affect suprachiasmatic nucleus cells and could play a role in modulating suprachiasmatic nucleus-mediated circadian rhythm entrainment.

  • Electrophysiological effects of pressure-ejected Bombesin-Like Peptides on hamster suprachiasmatic nucleus neurons in vitro.
    Journal of neuroendocrinology, 1993
    Co-Authors: Hugh D. Piggins, Benjamin Rusak
    Abstract:

    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.

Mary E. Sunday - One of the best experts on this subject based on the ideXlab platform.

  • Bombesin-Like Peptides Modulate Alveolarization and Angiogenesis in Bronchopulmonary Dysplasia
    American journal of respiratory and critical care medicine, 2007
    Co-Authors: Meera Subramaniam, Christine Bausch, Anne Twomey, Svetlana Andreeva, Bradley A. Yoder, Ling-yi Chang, James D. Crapo, Richard A. Pierce, Frank Cuttitta, Mary E. Sunday
    Abstract:

    Rationale: The incidence of bronchopulmonary dysplasia (BPD), a chronic lung disease of newborns, is paradoxically rising despite medical advances. We demonstrated elevated Bombesin-Like peptide levels in infants that later developed BPD. In the 140-day hyperoxic baboon model of BPD, anti-bombesin antibody 2A11 abrogated lung injury.Objectives: To test the hypothesis that Bombesin-Like Peptides mediate BPD in extremely premature baboons (born at Gestational Day 125 and given oxygen pro re nata [PRN], called the 125-day PRN model), similar to “modern-day BPD.”Methods: The 125-day animals were treated with 2A11 on Postnatal Day 1 (P1), P3, and P6. On P14 and P21, lungs were inflation-fixed for histopathologic analyses of alveolarization. Regulation of angiogenesis by bombesin was evaluated using cultured pulmonary microvascular endothelial cells.Measurements and Main Results: In 125-day PRN animals, urine Bombesin-Like peptide levels at P2–3 are directly correlated with impaired lung function at P14. Gastri...

  • Bombesin-Like Peptides and mast cell responses: relevance to bronchopulmonary dysplasia?
    American journal of respiratory and critical care medicine, 2003
    Co-Authors: Meera Subramaniam, Etsuko Wada, David H. Coy, York E. Miller, Kumiya Sugiyama, Yanping Kong, Peter F. Weller, Keiji Wada, Mary E. Sunday
    Abstract:

    Bombesin-Like Peptides (BLPs) are elevated in newborns who later develop bronchopulmonary dysplasia (BPD). In baboon models, anti-BLP blocking antibodies abrogate BPD. We now demonstrate hyperplasia of both neuroendocrine cells and mast cells in lungs of baboons with BPD, compared with non-BPD controls or BLP antibody-treated BPD baboons. To determine whether BLPs are proinflammatory, bombesin was administered intratracheally to mice. Forty-eight hours later, we observed increased numbers of lung mast cells. We analyzed murine mast cells for BLP receptor gene expression, and identified mRNAs encoding bombesin receptor subtype 3 and neuromedin-B receptor (NMB-R), but not gastrin-releasing peptide receptor. Only NMB-R-null mice accumulated fewer lung mast cells after bombesin treatment. Bombesin, gastrin-releasing peptide, NMB, and a bombesin receptor subtype 3-specific ligand induced mast cell proliferation and chemotaxis in vitro. These observations support a role for multiple BLPs in promoting mast cell responses, suggesting a mechanistic link between BLPs and chronic inflammatory lung diseases.

  • Bombesin-Like Peptides and receptors in normal fetal baboon lung: roles in lung growth and maturation.
    The American journal of physiology, 1999
    Co-Authors: Rodica L. Emanuel, J. S. Torday, N. Asokananthan, K. A. Sikorski, Mary E. Sunday
    Abstract:

    Previously, we have shown that Bombesin-Like peptide (BLP) promotes fetal lung development in rodents and humans but mediates postnatal lung injury in hyperoxic baboons. The present study analyzed the normal ontogeny of BLP and BLP receptors as well as the effects of BLP on cultured normal fetal baboon lungs. Transcripts encoding gastrin-releasing peptide (GRP), a pulmonary BLP, were detectable on gestational day 60 (ED60), peaked on approximately ED90, and then declined before term (ED180). Numbers of BLP-immunopositive neuroendocrine cells peaked from ED80 to ED125 and declined by ED160, preceding GRP-receptor mRNAs detected from ED125 until birth. BLP (0.1–10 nM) stimulated type II cell differentiation in organ cultures as assessed by [3H]choline incorporation into surfactant phospholipids, electron microscopy, and increased surfactant protein (SP) A- and/or SP-C-immunopositive cells and SP-A mRNA. BLP also induced neuroendocrine differentiation on ED60. Cell proliferation was induced by GRP, peaking on ED90. Similarly, blocking BLP degradation stimulated lung growth and maturation, which was completely reversed by a BLP-specific antagonist. The dissociation between GRP and GRP-receptor gene expression during ontogeny suggests that novel BLP receptors and/or Peptides might be implicated in these responses.

  • CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous Bombesin-Like Peptides.
    The Journal of clinical investigation, 1993
    Co-Authors: K. A. King, Margaret A. Shipp, Ji Hua, John S. Torday, Jeffrey M. Drazen, Sherry A. Graham, Mary E. Sunday
    Abstract:

    Bombesin-Like Peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs.

  • CD10/neutral endopeptidase 24.11 hydrolyzes Bombesin-Like Peptides and regulates the growth of small cell carcinomas of the lung
    Proceedings of the National Academy of Sciences of the United States of America, 1991
    Co-Authors: Margaret A. Shipp, George E. Tarr, Chang-yan Chen, Stephanie N. Switzer, Louis B. Hersh, Harald Stein, Mary E. Sunday, Ellis L. Reinherz
    Abstract:

    Bombesin-Like Peptides are essential autocrine growth factors for many small cell carcinomas (SCCas) of the lung. Herein, we demonstrate that these malignant pulmonary neuroendocrine cells express low levels of the cell surface metalloendopeptidase CD10/neutral endopeptidase 24.11 (CD10/NEP, common acute lymphoblastic leukemia antigen) and that this enzyme hydrolyzes Bombesin-Like Peptides. The growth of Bombesin-Like peptide-dependent SCC as is inhibited by CD10/NEP and potentiated by CD10/NEP inhibition. The results provide evidence that CD10/NEP is involved in the regulation of tumor cell proliferation. Since SCCa of the lung occurs almost exclusively in cigarette smokers and cigarette smoke inactivates CD10/NEP, decreased cell surface CD10/NEP enzymatic activity may be causally related to the development of SCCa of the lung.

York E. Miller - One of the best experts on this subject based on the ideXlab platform.

  • Bombesin-Like Peptides and mast cell responses: relevance to bronchopulmonary dysplasia?
    American journal of respiratory and critical care medicine, 2003
    Co-Authors: Meera Subramaniam, Etsuko Wada, David H. Coy, York E. Miller, Kumiya Sugiyama, Yanping Kong, Peter F. Weller, Keiji Wada, Mary E. Sunday
    Abstract:

    Bombesin-Like Peptides (BLPs) are elevated in newborns who later develop bronchopulmonary dysplasia (BPD). In baboon models, anti-BLP blocking antibodies abrogate BPD. We now demonstrate hyperplasia of both neuroendocrine cells and mast cells in lungs of baboons with BPD, compared with non-BPD controls or BLP antibody-treated BPD baboons. To determine whether BLPs are proinflammatory, bombesin was administered intratracheally to mice. Forty-eight hours later, we observed increased numbers of lung mast cells. We analyzed murine mast cells for BLP receptor gene expression, and identified mRNAs encoding bombesin receptor subtype 3 and neuromedin-B receptor (NMB-R), but not gastrin-releasing peptide receptor. Only NMB-R-null mice accumulated fewer lung mast cells after bombesin treatment. Bombesin, gastrin-releasing peptide, NMB, and a bombesin receptor subtype 3-specific ligand induced mast cell proliferation and chemotaxis in vitro. These observations support a role for multiple BLPs in promoting mast cell responses, suggesting a mechanistic link between BLPs and chronic inflammatory lung diseases.

  • Novel Bombesin-Like peptide binding proteins from lung.
    American journal of respiratory cell and molecular biology, 1994
    Co-Authors: Mark W. Geraci, York E. Miller, A Escobedo-morse, M A Kane
    Abstract:

    Gastrin-releasing peptide (GRP) and other Bombesin-Like Peptides (BLP) play an important role in lung development, response to injury, and carcinogenesis. However, the mRNAs from previously cloned BLP receptors are not detectable on Northern blots of normal lung. The purpose of this study was to isolate and characterize BLP binding proteins from normal mouse lung. Soluble cytoplasmic and detergent-solubilized membrane fractions were prepared from mouse lung and evaluated for specific 125I-GRP binding. Unexpectedly, not only the solubilized membrane but also the soluble cytoplasmic fractions demonstrated saturable, high-affinity, specific GRP binding activity with Kd = 1.6 nM, Bmax = 135 fmol/mg protein and Kd = 7.5 nM, Bmax = 323 fmol/mg protein, respectively. BLP binding proteins were isolated using GRP14-27 affinity chromatography and analyzed by SDS-PAGE. In each fraction, a major unique band of approximate M(r) = 70 kD was obtained and flanked by two weaker bands of approximate M(r) = 65 and 75 kD. Pr...

  • Urinary levels of Bombesin-Like Peptides in asymptomatic cigarette smokers: a potential risk marker for smoking-related diseases.
    Cancer Research, 1992
    Co-Authors: Samuel M. Aguayo, M A Kane, Talmadge E. King, Karen M. Sherritt, Wayne Silvers, Louise M. Nett, Thomas L. Petty, York E. Miller
    Abstract:

    Bombesin-Like Peptides (BLP) produced by pulmonary neuroendocrine cells have many physiological actions which are relevant to the pathobiology of cigarette smoking. The objectives of this study were to determine whether cigarette smokers excrete increased levels of BLP in their urine compared with nonsmokers, to determine the relationship between BLP levels in urine and bronchoalveolar lavage (BAL) fluid, and whether urinary BLP levels are merely a reflection of exposure to cigarette smoke. Simultaneous BAL fluid and urine samples were obtained from ten clinically normal smokers and 22 normal nonsmoker volunteers. Urine samples were also obtained from 39 normal smokers and 30 normal nonsmokers who did not have BAL performed. BLP levels were measured in urine and BAL fluid using an enzyme-linked immunoassay. Expired air content of carbon monoxide, which reflects recent exposure to cigarette smoke, was determined in 34 of the clinically normal smokers and correlated with urinary BLP levels. We found that, in addition to having increased BLP levels in BAL fluid ( P = 0.04), asymptomatic cigarette smokers also have increased BLP levels in their urine compared with normal nonsmokers ( P = 0.007). Of note, a subgroup of smokers have markedly increased BLP levels which do not overlap with the nonsmokers. Urinary BLP levels correlated with expired air content of carbon monoxide ( r = 0.49, P < 0.01). However, not all smokers with increased expired air content of carbon monoxide exhibited increased BLP levels. Finally, all smokers with detectable BLP levels in BAL fluid had detectable urinary BLP levels, and there was a positive correlation between BLP levels in urine and BAL fluid ( r = 0.625, P < 0.001). We conclude that a subgroup of asymptomatic cigarette smokers exhibit increased BLP levels, measurable in both urine and BAL fluid, which precede the onset of clinically detectable disease and which are not strictly dependent on smoking intensity. We speculate that smokers with increased BLP levels may have a greater risk for smoking-related diseases.