The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Carmen C. Pazos-moura - One of the best experts on this subject based on the ideXlab platform.
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<B>NeuromedinB> B receptor disruption impairs adipogenesis in mice and 3T3-L1 cells.
Journal of molecular endocrinology, 2019Co-Authors: Gabriela Sm Paula, Marianna Wilieman, Karina R Silva, Leandra Santos Baptista, Sihem Boudina, Luana L. Souza, Thais Bento-bernardes, Karina Dutra Asensi, Regina Coeli Dos Santos Goldenberg, Carmen C. Pazos-mouraAbstract:<B>NeuromedinB> B, a BomBesin-like peptide, and its receptor, are expressed in white adipose tissue with undefined roles. Female mice with disruption of <B>NeuromedinB> B receptor (NB-R) exhiBited partial resistance to diet-induced oBesity leading to our hypothesis that NB-R is involved in adipogenesis. Here, we showed that adipose stem/stromal cells (ASC) from perigonadal fat of female NB-R-knockout mice, exposed to a differentiation protocol in vitro, accumulated less lipid (45%) than wild type, suggesting reduced capacity to differentiate under adipogenic input. To further explore mechanisms, preadipocytes 3T3-L1 cells were incuBated in the presence of NB-R antagonist (PD168368) during the first 3 days in culture. Cells were analyzed in the end of the treatment (Day 3) and later when fully differentiated (Day 21). NB-R antagonist induced lower numBer of cells at day 3 and 21 (33-39%), reduced cell proliferation at day 3 (-53%) and reduced lipid accumulation at day 21 (-86%). The mRNA expressions of several adipocyte differentiation markers were importantly reduced at Both days: CeBpB and Pparg and FaBp4, Plin-1 and Adipoq, and additionally Lep mRNA at day 21. The antagonist had no effect when incuBated with mature 3T3-L1 adipocytes. Therefore, genetically disruption of NB-R in mice ASC or pharmacological antagonism of NB-R in 3T3-L1 cells impairs adipogenesis. The mechanisms suggested By results in 3T3-L1 cells involve reduction of cell proliferation and of early gene expressions, leading to decreased numBer of mature adipocytes. We speculate that NB-R antagonism may Be useful to limit the increase in adiposity due to pre-adipocyte differentiation.
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Hypothalamic-pituitary thyroid axis alterations in female mice with deletion of the <B>NeuromedinB> B receptor gene.
Regulatory peptides, 2014Co-Authors: Karen J Oliveira, Tania M. Ortiga-carvalho, Gabriela Sm Paula, Guinever E Império, Nina O Bressane, Carolina M A Magalhães, Leandro Miranda-alves, Carmen C. Pazos-mouraAbstract:<B>NeuromedinB> B, a peptide highly expressed at the pituitary, has Been shown to act as autocrine/paracrine inhiBitor of thyrotropin (TSH) release. Here we studied the thyroid axis of adult female mice lacking <B>NeuromedinB> B receptor (NBR-KO), compared to wild type (WT) littermates. They exhiBited slight increase in serum TSH (18%), with normal pituitary expression of mRNA coding for α-glycoprotein suBunit (Cga), But reduced TSH β-suBunit mRNA (TshB, 41%), lower intra-pituitary TSH content (24%) and increased thyroid hormone transporter MCT-8 (Slc16a2, 44%) and thyroid hormone receptor β mRNA expression (ThrB, 39%). NBR-KO mice exhiBited normal thyroxine (T4) and reduced triiodothyronine (T3) (30%), with no alterations in the intra-thyroidal content of T4 and T3 or thyroid morphological changes. Hypothalamic thyrotropin-releasing hormone (TRH) mRNA (Trh) was increased (68%), concomitant with a reduction in type 2 deiodinase mRNA (Dio2, 30%) and no changes in MCT-8 and thyroid hormone receptor mRNA expression. NBR-KO mice exhiBited a 56% higher increase in serum TSH in response to an acute single intraperitoneal injection of TRH concomitant with a non-significant increase in pituitary TRH receptor (Trhr) mRNA at Basal state. The phenotype of female NBR-KO mice at the hypothalamus-pituitary axis revealed alterations in pituitary and hypothalamic gene expression, associated with reduced serum T3, and higher TSH response to TRH, with apparently normal thyroid morphology and hormonal production. Thus, results confirm that <B>NeuromedinB> B pathways are importantly involved in secretory pathways of TSH and revealed its participation in the in vivo regulation of gene expression of TSH β-suBunit and pituitary MCT8 and ThrB and hypothalamic TRH and type 2 deiodinase.
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Impaired serum thyrotropin response to hypothyroidism in mice with disruption of <B>NeuromedinB> B receptor.
Regulatory Peptides, 2007Co-Authors: Karen J Oliveira, Tania M. Ortiga-carvalho, Adriana Cabanelas, Gabriela Sm Paula, Etsuko Wada, Keiji Wada, Marco Aurélio Liberato Costa Da Veiga, Carmen C. Pazos-mouraAbstract:ABstract <B>NeuromedinB> B (NB), a neuropeptide highly concentrated in pituitary, has Been proposed to Be an inhiBitor of thyrotropin (TSH) secretion. Previous study showed that mice with disruption of <B>NeuromedinB> B receptor (NBR-KO) have higher TSH release in response to thyrotropin-releasing hormone (TRH), although TSH seems to have decreased Bioactivity. Here we examined in NBR-KO mice the response of TSH to thyroid hormone (TH) deprivation, oBtained By methimazole treatment, or excess, oBtained By acute and chronic TH administration. In response to hypothyroidism NBR-KO mice exhiBited a lower magnitude increase in serum TSH compared to wild-type (WT) mice (1.7 vs. 3.3-times increase compared to euthyroid values, respectively, P 0.001). One hour after a single T4 injection (0.4μg/100 g BW), WT and NBR-KO hypothyroid mice presented similar degree of serum TSH reduction (54%, P 0.05). However, 3 h after T4 administration, WT mice presented serum TSH similar to hypothyroid Baseline, while NBR-KO mice still had decreased serum TSH (30% reduced in comparison to hypothyroid Baseline P 0.05). T3 treatment of euthyroid mice for 21 days, with progressively increasing doses, significantly reduced serum TSH similarly in WT and NBR-KO mice. Also, serum T4 exhiBited the same degree of suppression in WT and NBR-KO. In conclusion, disruption of <B>NeuromedinB> B receptor did not interfere with the sensitivity of thyroid hormone-mediated suppression of TSH release, But impaired the aBility of thyrotroph to increase serum TSH in hypothyroidism, which highlights the importance of NB in modulating the set point of the hypothalamus–pituitary–thyroid axis at hypothyroidism.
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Impaired serum thyrotropin response to hypothyroidism in mice with disruption of <B>NeuromedinB> B receptor.
Regulatory peptides, 2007Co-Authors: Karen J Oliveira, Tania M. Ortiga-carvalho, Adriana Cabanelas, Marco Aurélio Lc Veiga, Gabriela Sm Paula, Etsuko Wada, Keiji Wada, Carmen C. Pazos-mouraAbstract:<B>NeuromedinB> B (NB), a neuropeptide highly concentrated in pituitary, has Been proposed to Be an inhiBitor of thyrotropin (TSH) secretion. Previous study showed that mice with disruption of <B>NeuromedinB> B receptor (NBR-KO) have higher TSH release in response to thyrotropin-releasing hormone (TRH), although TSH seems to have decreased Bioactivity. Here we examined in NBR-KO mice the response of TSH to thyroid hormone (TH) deprivation, oBtained By methimazole treatment, or excess, oBtained By acute and chronic TH administration. In response to hypothyroidism NBR-KO mice exhiBited a lower magnitude increase in serum TSH compared to wild-type (WT) mice (1.7 vs. 3.3-times increase compared to euthyroid values, respectively, P
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Estrogen modulates <B>NeuromedinB> B effects on thyrotropin and prolactin release in vitro
Life sciences, 2003Co-Authors: Rachel Moraes Moreira, F. H. Curty, Patricia Cristina Lisboa, Daniele Amaral, Tania M. Ortiga-carvalho, Carmen C. Pazos-mouraAbstract:ABstract <B>NeuromedinB> B(NB), a BomBesin-like peptide, has Been shown to inhiBit thyrotropin (TSH) release in pituitary explants of male rats and to stimulate Prolactin (PRL) release in male pituitary cell cultures. We investigated the effect of estrogen status of female rats on the response of thyrotrophs and lactotrophs to <B>NeuromedinB> B (NB) in vitro. Ovariectomized rats were treated with near-physiological or high doses of 17β estradiol Benzoate (0.7 or 14 EB μg/100 gBW/daily, 10 days) or with vehicle (OVX). EB treatment induced a dose-dependent increase in serum prolactin and an increase in pituitary NB content, measured By specific RIA, that was similar in Both EB groups (P −7 M NB. OVX + EB0.7 glands responded to NB with a not statistically significant dose-dependent decrease in TSH release. However, glands from hyperestrogenized rats (OVX + EB14) required a higher dose (10 −5 M) of NB to inhiBit TSH release (P −5 M NB only in glands of hyperestrogenized rats, while no effect of NB was oBserved in the other groups. In conclusion, estrogen status of female rats modulates the inhiBitory effect of NB on TSH release in vitro and hyperestrogenism is required for stimulatory effect of NB on PRL release in vitro. It is suggested that the induction of PRL release By <B>NeuromedinB> B is a pharmacological rather than a physiological effect, But <B>NeuromedinB> B may contriBute to the increased release of PRL associated with hyperestrogenism.
Robert T. Jensen - One of the best experts on this subject based on the ideXlab platform.
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Comparative Pharmacology of the Nonpeptide <B>NeuromedinB> B Receptor Antagonist PD 168368
2016Co-Authors: Richard R. Ryan, Samuel A. Mantey, David H. Coy, Tatsuro Katsuno, Tapas K. Pradhan, Christian H. Weber, James F. Battey, Robert T. JensenAbstract:The mammalian peptide <B>NeuromedinB> B (NMB) and its receptor are expressed in a variety of tissues; however, little is defini-tively estaBlished aBout its physiological actions Because of the lack of potent, specific antagonists. Recently, the peptoid PD 168368 was found to Be a potent human NMB receptor antag-onist. Because it had Been shown previously that either syn-thetic analogs of BomBesin (Bn) or other receptor peptoid or receptor antagonists function as an antagonist or agonist de-pends on animal species and receptor suBtype studied, we investigated the pharmacological properties of PD 168368 compared with all currently known Bn receptor suBtypes (NMB receptor, gastrin-releasing peptide receptor, Bn receptor suB-type 3, and Bn receptor suBtype 4) from human, mouse, rat, and frog. In Binding studies, PD 168368 had similar high affin
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<B>NeuromedinB> B receptors regulate EGF receptor tyrosine phosphorylation in lung cancer cells
European Journal of Pharmacology, 2010Co-Authors: Terry W. Moody, Samuel A. Mantey, Marc J. Berna, Veronica Sancho, Lisa A. Ridnour, David A. Wink, Daniel Chan, Giuseppe Giaccone, Robert T. JensenAbstract:<B>NeuromedinB> B (NMB), a memBer of the BomBesin family of peptides, is an autocrine growth factor for many lung cancer cells. The present study investigated the aBility of NMB to cause transactivation of the epidermal growth factor (EGF) receptor in lung cancer cells. By Western Blot, addition of NMB or related peptides to NCI-H1299 human non-small cell lung cancer (NSCLC) cells, caused phosphorylation of Tyr1068 of the EGF receptor. The signal was amplified using NCI-H1299 cells staBly transected with NMB receptors. The transactivation of the EGF receptor or the tyrosine phosphorylation of ERK caused By NMB-like peptides was inhiBited By AG1478 or gefitiniB (tyrosine kinase inhiBitors) and NMB receptor antagonist PD168368 But not the GRP receptor antagonist, BW2258U89. The transactivation of the EGF receptor caused By NMB-like peptides was inhiBited By GM6001 (matrix metalloprotease inhiBitor), PP2 (Src inhiBitor), or transforming growth factor (TGF)α antiBody. The transactivation of the EGF receptor and the increase in reactive oxygen species caused By NMB-like peptides was inhiBited By N-acetylcysteine (NAC) or Tiron. GefitiniB inhiBited the proliferation of NCI-H1299 cells and its sensitivity was increased By the addition of PD168368. The results indicate that the NMB receptor regulates EGF receptor transactivation By a mechanism dependent on Src as well as metalloprotease activation and generation of reactive oxygen species.
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Nonpeptide <B>NeuromedinB> B receptor antagonists inhiBit the proliferation of C6 cells.
European journal of pharmacology, 2000Co-Authors: Terry W. Moody, Robert T. Jensen, Luis J. Garcı́a, Julius LeytonAbstract:The aBility of nonpeptide antagonists to interact with <B>NeuromedinB> B receptors on C6 cells was investigated. 2-[3-(2, 6-Diisopropyl-phenyl)-ureido]3-(1H-indol-3-yl)-2-methyl-N-(1-pyridin- 2-yl-cyclohexylmethyl)-proprionate (PD165929), 3-(1H-indol-3-yl)-2-methyl-2-[3(4-nitro-phenyl)-ureido]-N-(1-pyridin- 2-yl-cyclohexylmethyl)-propionamide (PD168368) and 3-(1H-indol-3-yl)-N-[1-(5-methoxy-pyridin-2-yl)-cyclohexylmethyl]- 2-m ethyl-2-[3-(4-nitro-phenyl)-ureido]-propionamide (PD176252) inhiBited (125I-Tyr0)<B>NeuromedinB> B Binding with IC50 values of 2000, 40 and 50 nM, respectively. Because <B>NeuromedinB> B is a G-protein coupled serpentine receptor, the effects of <B>NeuromedinB> B antagonists on second messenger production and proliferation were investigated. PD168368 inhiBited the aBility of 10 nM <B>NeuromedinB> B to cause elevation of cytosolic Ca2+, whereas it had no effect on Basal cytosolic Ca2+. PD168368 inhiBited the aBility of 100 nM <B>NeuromedinB> B to cause elevation of c-fos mRNA. Also, PD168368 in a dose-dependent manner inhiBited the aBility of 100 nM <B>NeuromedinB> B to cause phosphorylation of focal adhesion kinase. Using a [3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium Bromide] assay, the order of antagonist potency to inhiBit C6 proliferation was PD168368=PD176252>PD165929. Also, 1 microM PD168368 and PD176252 significantly inhiBited colony numBer using a proliferation assay in vitro. PD168368 significantly inhiBited C6 xenograft growth in nude mice in vivo. These results indicate that PD168368 is a C6 cell <B>NeuromedinB> B receptor antagonist, which inhiBits proliferation.
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comparative pharmacology of the nonpeptide <B>NeuromedinB> B receptor antagonist pd 168368
Journal of Pharmacology and Experimental Therapeutics, 1999Co-Authors: Richard R. Ryan, Samuel A. Mantey, David H. Coy, Tatsuro Katsuno, Tapas K. Pradhan, James F. Battey, H C Weber, Robert T. JensenAbstract:The mammalian peptide <B>NeuromedinB> B (NMB) and its receptor are expressed in a variety of tissues; however, little is definitively estaBlished aBout its physiological actions Because of the lack of potent, specific antagonists. Recently, the peptoid PD 168368 was found to Be a potent human NMB receptor antagonist. Because it had Been shown previously that either synthetic analogs of BomBesin (Bn) or other receptor peptoid or receptor antagonists function as an antagonist or agonist depends on animal species and receptor suBtype studied, we investigated the pharmacological properties of PD 168368 compared with all currently known Bn receptor suBtypes (NMB receptor, gastrin-releasing peptide receptor, Bn receptor suBtype 3, and Bn receptor suBtype 4) from human, mouse, rat, and frog. In Binding studies, PD 168368 had similar high affinities ( K i = 15–45 nM) for NMB receptors from each species examined, 30- to 60-fold lower affinity for gastrin-releasing peptide receptors, and >300-fold lower affinity for Bn receptor suBtype 3 or 4. It inhiBited NMB Binding in a competitive manner. PD 168368 alone did not stimulate increases in either intracellular calcium concentration or [3H]inositol phosphates in any of the cells studied But inhiBited NMB-induced responses with equivalent potencies in cells containing NMB receptors. PD 168368 was only minimally soluBle in water. When hydroxypropyl-β-cyclodextrin rather than dimethyl sulfoxide was used as the vehicle, Both the affinity and the antagonist potency of PD 168368 were significantly greater. The results demonstrate that PD 168368 is a potent, competitive, and selective antagonist at NMB receptors, with a similar pharmacology across animal species. PD 168368 should prove useful for delineating the Biological role of NMB and selectively Blocking NMB signaling in Bioassays and as a lead for the development of more selective nonpeptide antagonists for the NMB receptor.
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Four amino acid residues are critical for high affinity Binding of <B>NeuromedinB> B to the <B>NeuromedinB> B receptor.
The Journal of biological chemistry, 1998Co-Authors: Eduardo Sainz, Samuel A. Mantey, Robert T. Jensen, Mark Akeson, James F. BatteyAbstract:ABstract Three mammalian BomBesin receptor suBtypes have Been characterized: the gastrin-releasing peptide receptor (GRP-R), the <B>NeuromedinB> B receptor (NMB-R), and BomBesin receptor suBtype 3 (BRS-3). In a previous report we identified four amino acids that are critical for high affinity Binding of BomBesin and gastrin-releasing peptide (GRP) to the GRP-R. These four amino acids are conserved in all species variants of the GRP-R and NMB-R which Bind BomBesin with high affinity, But they are diverged in BRS-3, the BomBesin receptor suBtype that Binds BomBesin with much lower affinity. SuBstituting these four divergent amino acids in BRS-3 for the conserved amino acids in either GRP-R or NMB-R increased the affinity of the mutated BRS-3 (4ΔBRS-3) for BomBesin compared with wild-type BRS-3. We hypothesized that the same four amino acids might Be critical for high affinity NMB Binding to the NMB-R. In this study we confirm this hypothesis By showing that the affinity of NMB is increased in a mutant BRS-3 receptor (4ΔBRS-3) that contains these four suBstitutions resulting in an affinity that is close to the affinity of wild-type NMB-R for NMB. In contrast, these four amino acid suBstitutions in BRS-3 did not result in the formation of a high affinity Binding site for the recently descriBed non-peptide NMB-R antagonist PD168368.
James F. Battey - One of the best experts on this subject based on the ideXlab platform.
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Comparative Pharmacology of the Nonpeptide <B>NeuromedinB> B Receptor Antagonist PD 168368
2016Co-Authors: Richard R. Ryan, Samuel A. Mantey, David H. Coy, Tatsuro Katsuno, Tapas K. Pradhan, Christian H. Weber, James F. Battey, Robert T. JensenAbstract:The mammalian peptide <B>NeuromedinB> B (NMB) and its receptor are expressed in a variety of tissues; however, little is defini-tively estaBlished aBout its physiological actions Because of the lack of potent, specific antagonists. Recently, the peptoid PD 168368 was found to Be a potent human NMB receptor antag-onist. Because it had Been shown previously that either syn-thetic analogs of BomBesin (Bn) or other receptor peptoid or receptor antagonists function as an antagonist or agonist de-pends on animal species and receptor suBtype studied, we investigated the pharmacological properties of PD 168368 compared with all currently known Bn receptor suBtypes (NMB receptor, gastrin-releasing peptide receptor, Bn receptor suB-type 3, and Bn receptor suBtype 4) from human, mouse, rat, and frog. In Binding studies, PD 168368 had similar high affin
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comparative pharmacology of the nonpeptide <B>NeuromedinB> B receptor antagonist pd 168368
Journal of Pharmacology and Experimental Therapeutics, 1999Co-Authors: Richard R. Ryan, Samuel A. Mantey, David H. Coy, Tatsuro Katsuno, Tapas K. Pradhan, James F. Battey, H C Weber, Robert T. JensenAbstract:The mammalian peptide <B>NeuromedinB> B (NMB) and its receptor are expressed in a variety of tissues; however, little is definitively estaBlished aBout its physiological actions Because of the lack of potent, specific antagonists. Recently, the peptoid PD 168368 was found to Be a potent human NMB receptor antagonist. Because it had Been shown previously that either synthetic analogs of BomBesin (Bn) or other receptor peptoid or receptor antagonists function as an antagonist or agonist depends on animal species and receptor suBtype studied, we investigated the pharmacological properties of PD 168368 compared with all currently known Bn receptor suBtypes (NMB receptor, gastrin-releasing peptide receptor, Bn receptor suBtype 3, and Bn receptor suBtype 4) from human, mouse, rat, and frog. In Binding studies, PD 168368 had similar high affinities ( K i = 15–45 nM) for NMB receptors from each species examined, 30- to 60-fold lower affinity for gastrin-releasing peptide receptors, and >300-fold lower affinity for Bn receptor suBtype 3 or 4. It inhiBited NMB Binding in a competitive manner. PD 168368 alone did not stimulate increases in either intracellular calcium concentration or [3H]inositol phosphates in any of the cells studied But inhiBited NMB-induced responses with equivalent potencies in cells containing NMB receptors. PD 168368 was only minimally soluBle in water. When hydroxypropyl-β-cyclodextrin rather than dimethyl sulfoxide was used as the vehicle, Both the affinity and the antagonist potency of PD 168368 were significantly greater. The results demonstrate that PD 168368 is a potent, competitive, and selective antagonist at NMB receptors, with a similar pharmacology across animal species. PD 168368 should prove useful for delineating the Biological role of NMB and selectively Blocking NMB signaling in Bioassays and as a lead for the development of more selective nonpeptide antagonists for the NMB receptor.
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Four amino acid residues are critical for high affinity Binding of <B>NeuromedinB> B to the <B>NeuromedinB> B receptor.
The Journal of biological chemistry, 1998Co-Authors: Eduardo Sainz, Samuel A. Mantey, Robert T. Jensen, Mark Akeson, James F. BatteyAbstract:ABstract Three mammalian BomBesin receptor suBtypes have Been characterized: the gastrin-releasing peptide receptor (GRP-R), the <B>NeuromedinB> B receptor (NMB-R), and BomBesin receptor suBtype 3 (BRS-3). In a previous report we identified four amino acids that are critical for high affinity Binding of BomBesin and gastrin-releasing peptide (GRP) to the GRP-R. These four amino acids are conserved in all species variants of the GRP-R and NMB-R which Bind BomBesin with high affinity, But they are diverged in BRS-3, the BomBesin receptor suBtype that Binds BomBesin with much lower affinity. SuBstituting these four divergent amino acids in BRS-3 for the conserved amino acids in either GRP-R or NMB-R increased the affinity of the mutated BRS-3 (4ΔBRS-3) for BomBesin compared with wild-type BRS-3. We hypothesized that the same four amino acids might Be critical for high affinity NMB Binding to the NMB-R. In this study we confirm this hypothesis By showing that the affinity of NMB is increased in a mutant BRS-3 receptor (4ΔBRS-3) that contains these four suBstitutions resulting in an affinity that is close to the affinity of wild-type NMB-R for NMB. In contrast, these four amino acid suBstitutions in BRS-3 did not result in the formation of a high affinity Binding site for the recently descriBed non-peptide NMB-R antagonist PD168368.
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<B>NeuromedinB> B receptor, expressed in Xenopus laevis oocytes, selectively couples to Gαq and not Gα11
FEBS letters, 1994Co-Authors: Hagit Shapira, James M. Way, Dafna Lipinsky, Yoram Oron, James F. BatteyAbstract:G-proteins of the q family have Been implicated as mediators of BomBesin receptors action. We cloned Xenopus Gαq and Gα11 and specifically disrupted the synthesis of either protein with selective antisense oligonucleotides. Gαq antisense inhiBited responses mediated By <B>NeuromedinB> B receptor (NMB-R) By 74%, though not By gastrin-releasing peptide receptor (GRP-R). Gα11 antisense had little effect on either GRP-R- or NMB-R-mediated responses. This suggests that NMB-R couples to Gαq, and that GRP-R and NMB-R show distinct G-protein coupling preferences in the Xenopus oocyte.
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<B>NeuromedinB>-B receptor transfected BALB/3T3 cells: signal transduction and effects of ectopic receptor expression on cell growth
Regulatory peptides, 1993Co-Authors: David Dobrzanski, Etsuko Wada, James F. Battey, Yoav Sharoni, Edward A. SausvilleAbstract:BomBesin-like peptides including <B>NeuromedinB> 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, <B>NeuromedinB>-B is potentially a Bifunctional regulator of cell growth.
Keiji Wada - One of the best experts on this subject based on the ideXlab platform.
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Functional Properties of Two BomBesin-Like Peptide Receptors Revealed By the Analysis of Mice Lacking <B>NeuromedinB> B Receptor
2013Co-Authors: Hiroko Ohki-hamazaki, Kazuyuki Yamada, Yasushi Sakai, Katsuo Kamata, Hiroo Ogura, Shigeru Okuyama, Kei Watase, Keiji WadaAbstract:The <B>NeuromedinB> B-preferring receptor (NMB-R) is one of the memBers of the BomBesin (BN)-like peptide receptor suBfamily in mammals. Previously, we have generated and characterized mice with targeted disruption of the two other BN-like peptide receptors, BomBesin receptor suBtype-3 (BRS-3) and gastrinreleasing peptide-preferring receptor (GRP-R). Here we descriBe the generation and analysis of NMB-R-deficient mice to investigate how NMB-R differs from BRS-3 and GRP-R. Compensation for NMB-R deficiency By overexpression of GRP-R and/or BRS-3 was not detected. Although the hypothermic effect of NMB was reduced By 50 % in NMB-R-deficient mice, the effect of GRP infusion was comparaBle to the wild-type mice. In contrast, fundic smooth muscle contraction on stimulation with NMB or GRP was normal in NMB-R-deficient mice. Administration of GRP But not NMB suppressed glucose intak
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Impaired serum thyrotropin response to hypothyroidism in mice with disruption of <B>NeuromedinB> B receptor.
Regulatory Peptides, 2007Co-Authors: Karen J Oliveira, Tania M. Ortiga-carvalho, Adriana Cabanelas, Gabriela Sm Paula, Etsuko Wada, Keiji Wada, Marco Aurélio Liberato Costa Da Veiga, Carmen C. Pazos-mouraAbstract:ABstract <B>NeuromedinB> B (NB), a neuropeptide highly concentrated in pituitary, has Been proposed to Be an inhiBitor of thyrotropin (TSH) secretion. Previous study showed that mice with disruption of <B>NeuromedinB> B receptor (NBR-KO) have higher TSH release in response to thyrotropin-releasing hormone (TRH), although TSH seems to have decreased Bioactivity. Here we examined in NBR-KO mice the response of TSH to thyroid hormone (TH) deprivation, oBtained By methimazole treatment, or excess, oBtained By acute and chronic TH administration. In response to hypothyroidism NBR-KO mice exhiBited a lower magnitude increase in serum TSH compared to wild-type (WT) mice (1.7 vs. 3.3-times increase compared to euthyroid values, respectively, P 0.001). One hour after a single T4 injection (0.4μg/100 g BW), WT and NBR-KO hypothyroid mice presented similar degree of serum TSH reduction (54%, P 0.05). However, 3 h after T4 administration, WT mice presented serum TSH similar to hypothyroid Baseline, while NBR-KO mice still had decreased serum TSH (30% reduced in comparison to hypothyroid Baseline P 0.05). T3 treatment of euthyroid mice for 21 days, with progressively increasing doses, significantly reduced serum TSH similarly in WT and NBR-KO mice. Also, serum T4 exhiBited the same degree of suppression in WT and NBR-KO. In conclusion, disruption of <B>NeuromedinB> B receptor did not interfere with the sensitivity of thyroid hormone-mediated suppression of TSH release, But impaired the aBility of thyrotroph to increase serum TSH in hypothyroidism, which highlights the importance of NB in modulating the set point of the hypothalamus–pituitary–thyroid axis at hypothyroidism.
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Impaired serum thyrotropin response to hypothyroidism in mice with disruption of <B>NeuromedinB> B receptor.
Regulatory peptides, 2007Co-Authors: Karen J Oliveira, Tania M. Ortiga-carvalho, Adriana Cabanelas, Marco Aurélio Lc Veiga, Gabriela Sm Paula, Etsuko Wada, Keiji Wada, Carmen C. Pazos-mouraAbstract:<B>NeuromedinB> B (NB), a neuropeptide highly concentrated in pituitary, has Been proposed to Be an inhiBitor of thyrotropin (TSH) secretion. Previous study showed that mice with disruption of <B>NeuromedinB> B receptor (NBR-KO) have higher TSH release in response to thyrotropin-releasing hormone (TRH), although TSH seems to have decreased Bioactivity. Here we examined in NBR-KO mice the response of TSH to thyroid hormone (TH) deprivation, oBtained By methimazole treatment, or excess, oBtained By acute and chronic TH administration. In response to hypothyroidism NBR-KO mice exhiBited a lower magnitude increase in serum TSH compared to wild-type (WT) mice (1.7 vs. 3.3-times increase compared to euthyroid values, respectively, P
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Stress-induced impairment of inhiBitory avoidance learning in female <B>NeuromedinB> B receptor-deficient mice.
Physiology & behavior, 2003Co-Authors: Kazuyuki Yamada, Yuko Santo-yamada, Keiji WadaAbstract:<B>NeuromedinB> B (NMB) is a mammalian BomBesin (BN)-like peptide that exerts its function via the <B>NeuromedinB> B receptor (NMB-R). The NMB/NMB-R system is involved in stress response, and therefore we examined Behavioral properties in female mice lacking NMB-R using a restraint-induced stress paradigm. Thirty minutes of restraint in a wire mesh cage constituted a sufficient stress stimulus for mice as evidenced By elevated Blood glucose concentrations in stressed wild-type and NMB-R-deficient mice. Using a one-trial passive avoidance test, stressed NMB-R-deficient mice exhiBited a marked reduction in memory performance. NMB-R-deficient mice exhiBited elevated spontaneous activity in a novel environment compared to non-stressed mutant mice after 30-min stress, and a similar difference was also oBserved Between stressed/non-stressed wild-type mice. An elevated plus maze test showed that the stress stimulus had no effect on anxiety in either wild-type or NMB-R-deficient mice. Furthermore, pain response of wild-type and NMB-R-deficient mice induced By electric foot shock was not affected under either stressed or non-stressed conditions. These results indicate that impaired memory performance in stressed NMB-R-deficient mice is not a consequence of changes in spontaneous activity, anxiety, or pain response, and suggest that the NMB/NMB-R pathway may play a role in regulating the stress response via the neural system that controls learning and memory.
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Restraint stress impaired maternal Behavior in female mice lacking the <B>NeuromedinB> B receptor (NMB-R) gene
Neuroscience letters, 2002Co-Authors: Kazuyuki Yamada, Yuko Santo-yamada, Keiji WadaAbstract:<B>NeuromedinB> B (NMB) is a BomBesin-like peptide that exerts its function via NMB receptor (NMB-R). The NMB/NMB-R pathway is involved in the regulation of a wide variety of Behaviors, such as spontaneous activity, feeding, and anxiety-related Behavior. In the current study, we assessed the effects of stress on maternal Behavior in female NMB-R-deficient mice. Non-stressed NMB-R-deficient and wild-type mice showed normal maternal Behavior. However, immediately after undergoing restraint-induced stress (30 min) Both genotypes of mice exhiBited severely decreased maternal Behaviors. Furthermore, 30 min after stress induction, maternal Behavior in wild-type mice recovered to near normal levels whereas that of NMB-R-deficient mice remained significantly lower. These results indicate that NMB-R-deficient mice suffer more severely from stress and suggest that dysfunction in the NMB/NMB-R pathway may constitute one of the risk factors of stress vulneraBility.
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BomBesin/GRP-preferring and <B>NeuromedinB> B-preferring receptors in the rat urogenital system.
Neuropeptides, 2004Co-Authors: W. Randal Kilgore, Douglas C Mcvey, Patrick W Mantyh, Christopher R Mantyh, Steven R VignaAbstract:ABstract BomBesin Binding sites were localized in the rat urogenital system By autoradiography of 125I-Tyr4-BomBesin Binding to frozen tissue sections. SaturaBle Binding was oBserved in the Bladder, seminal vesicle, uterus, and oviduct. In all organs, the Binding sites corresponded to layers of smooth muscle. Radioligand Binding studies were performed on homogenized memBrane preparations from Bladder, uterus, and seminal vesicle. MemBrane Binding was saturaBle, reversiBle, time- and temperature-dependent, and specific for BomBesin and related peptides. Analysis of saturaBle equiliBrium Binding from all three organs yielded a Best fit to a one-site model of high affinity Binding with apparent Kds of 720 pM for Bladder, 470 pM for uterus, and 700 pM for seminal vesicle. <B>NeuromedinB> B was potent in displacing saturaBle 125I-Tyr4-BomBesin Binding from Bladder and seminal vesicle But not uterus memBranes. In order to characterize these Binding sites further, the aBility of these memBranes to interact with a specific BomBesin receptor antagonist, [Leu13-psi-CH2NH-Leu14]-BomBesin, and with GTP-gamma-S was determined. [Leu13-psi-CH2NH-Leu14]-BomBesin was much more potent in displacing saturaBle 125I-Tyr4-BomBesin Binding from uterus than from Bladder and seminal vesicle memBranes, further supporting the distinction Between the uterus and the Bladder/seminal vesicle Binding sites as BomBesin receptor suBtypes. GTP-gamma-S inhiBited saturaBle 125I-Tyr4-BomBesin Binding to memBranes from all three organs, indicating that Both receptor suBtypes are linked to GTP-Binding proteins. We conclude that smooth muscle in the rat urogenital system expresses BomBesin receptors and that endogenous GRP and <B>NeuromedinB> B may regulate some reproductive and excretory functions. The Bladder and seminal vesicle express the <B>NeuromedinB> B-preferring suBtype and the uterus expresses the BomBesin/GRP-preferring suBtype of BomBesin receptor.
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BomBesin grp preferring and <B>NeuromedinB> B preferring receptors in the rat urogenital system
Neuropeptides, 1993Co-Authors: W. Randal Kilgore, Douglas C Mcvey, Patrick W Mantyh, Christopher R Mantyh, Steven R VignaAbstract:ABstract BomBesin Binding sites were localized in the rat urogenital system By autoradiography of 125I-Tyr4-BomBesin Binding to frozen tissue sections. SaturaBle Binding was oBserved in the Bladder, seminal vesicle, uterus, and oviduct. In all organs, the Binding sites corresponded to layers of smooth muscle. Radioligand Binding studies were performed on homogenized memBrane preparations from Bladder, uterus, and seminal vesicle. MemBrane Binding was saturaBle, reversiBle, time- and temperature-dependent, and specific for BomBesin and related peptides. Analysis of saturaBle equiliBrium Binding from all three organs yielded a Best fit to a one-site model of high affinity Binding with apparent Kds of 720 pM for Bladder, 470 pM for uterus, and 700 pM for seminal vesicle. <B>NeuromedinB> B was potent in displacing saturaBle 125I-Tyr4-BomBesin Binding from Bladder and seminal vesicle But not uterus memBranes. In order to characterize these Binding sites further, the aBility of these memBranes to interact with a specific BomBesin receptor antagonist, [Leu13-psi-CH2NH-Leu14]-BomBesin, and with GTP-gamma-S was determined. [Leu13-psi-CH2NH-Leu14]-BomBesin was much more potent in displacing saturaBle 125I-Tyr4-BomBesin Binding from uterus than from Bladder and seminal vesicle memBranes, further supporting the distinction Between the uterus and the Bladder/seminal vesicle Binding sites as BomBesin receptor suBtypes. GTP-gamma-S inhiBited saturaBle 125I-Tyr4-BomBesin Binding to memBranes from all three organs, indicating that Both receptor suBtypes are linked to GTP-Binding proteins. We conclude that smooth muscle in the rat urogenital system expresses BomBesin receptors and that endogenous GRP and <B>NeuromedinB> B may regulate some reproductive and excretory functions. The Bladder and seminal vesicle express the <B>NeuromedinB> B-preferring suBtype and the uterus expresses the BomBesin/GRP-preferring suBtype of BomBesin receptor.