Pro-nociceptive effects of neuromedin u in rat

Yu, Xiao Hong; Cao, Chang; Mennicken, Françoise; Puma, Carole; Dray, A.; O’Donnell, Dajan; Ahmad, Sultan; Perkins, M.N.

doi:10.1016/s0306-4522(03)00300-2

Cited by 53 publications

(76 citation statements)

References 22 publications

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“…Interestingly, this anorexigenic effect was more potent and persistent than that observed with the same dose of NMU. Antagonists to NMUR1 could inhibit mast cell-mediated inflammatory diseases (Moriyama et al, 2005), whereas other drugs might be suitable to test for the reduction of cancer pain, as NMU has a pronociceptive role in mice and rats Yu et al, 2003). It is possible that such antagonists will not only be useful in cancer cachexia but also in reducing tumor recurrence and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia

McRoberts

Berr

et al. 2006

Oncogene

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Most deaths from urinary bladder cancer are owing to metastatic disease. A reduction in Rho GDP Dissociation Inhibitor 2 (RhoGDI2) protein has been associated with increased risk of metastasis in patients with locally advanced bladder cancer, whereas in animal models, RhoGDI2 reconstitution in cells without expression results in lung metastasis suppression. Recently, we noted an inverse correlation between tumor RhoGDI2 and Neuromedin U (NMU) expression, suggesting that NMU might be a target of the lung metastasis suppressor effect of RhoGDI2. Here we evaluated whether NMU is regulated by RhoGDI2 and is functionally important in tumor progression. We used small interfering RNA knockdown of endogenous RhoGDI2 in poorly tumorigenic and nonmetastatic human bladder cancer T24 cells and observed increased NMU RNA expression. Although NMU overexpression did not increase the monolayer growth of T24 or related T24T poorly metastatic human bladder cancer cells, it did augment anchorage-independent growth for the latter. Overexpression of NMU in T24 and T24T cells significantly promoted tumor formation of both cell lines in nude mice, but did not alter the growth rate of established tumors. Furthermore, NMU-overexpressing xenografts were associated with lower animal body weight than control tumors, indicating a possible role of NMU in cancer cachexia. NMU overexpression in T24T cells significantly enhanced their lung metastatic ability. Bioluminescent in vivo imaging revealed that lung metastases in T24T grew faster than the same tumors in the subcutaneous microenvironment. In conclusion, NMU is a RhoGDI2-regulated gene that appears important for tumorigenicity, lung metastasis and cancer cachexia, and thus a promising therapeutic target in cancer.

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Section: Discussionmentioning

confidence: 99%

Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia

McRoberts

Berr

et al. 2006

Oncogene

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“…Early characterizations of NmU revealed its potent contractile activity in the rat uterus (6, 7) which were followed by experiments demonstrating contraction of smooth muscle of many organs (8,9). Several studies indicate that NmU also plays a role in energy homeostasis, (10 -13) regulation of blood pressure (14,15), and nociception (16,17). Taken together, these reports indicate a wide variety of functions for NmU and suggest potential mechanisms by which release of signaling molecules from neurons can mediate processes both within the CNS and in peripheral tissues.…”

Section: T Ype-2 Th (Th2) Cells Are Cd4mentioning

confidence: 99%

Neuromedin Elicits Cytokine Release in Murine Th2-Type T Cell Clone D10.G4.1

Johnson

Appelbaum²,

Carptenter

et al. 2004

The Journal of Immunology

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Neuromedin U (NmU), originally isolated from porcine spinal cord and later from other species, is a novel peptide that potently contracts smooth muscle. NmU interacts with two G protein-coupled receptors designated as NmU-1R and NmU-2R. This study demonstrates a potential proinflammatory role for NmU. In a mouse Th2 cell line (D10.G4.1), a single class of high affinity saturable binding sites for 125I-labeled NmU (KD 364 pM and Bmax 1114 fmol/mg protein) was identified, and mRNA encoding NmU-1R, but not NmU-2R, was present. Competition binding analysis revealed equipotent, high affinity binding of NmU isopeptides to membranes prepared from D10.G4.1 cells. Exposure of these cells to NmU isopeptides resulted in an increase in intracellular Ca2+ concentration (EC50 4.8 nM for human NmU). In addition, NmU also significantly increased the synthesis and release of cytokines including IL-4, IL-5, IL-6, IL-10, and IL-13. Studies using pharmacological inhibitors indicated that maximal NmU-evoked cytokine release required functional phospholipase C, calcineurin, MEK, and PI3K pathways. These data suggest a role for NmU in inflammation by stimulating cytokine production by T cells.

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“…Although NMS shares a C-terminal core structure (7-amino acid residues) with NMU and activates recombinant NMUR1 and NMUR2 expressed in Chinese hamster ovary cells with almost the same affinity as NMU, NMS is not a splice variant of NMU because the NMS and NMU genes have been mapped to discrete chromosomes . In addition, although NMU mRNA has been detected in peripheral and central organs (Howard et al 2000, Yu et al 2003, Ivanov et al 2004, the distribution of NMS is limited to the testis, spleen, and SCN .…”

Section: Introductionmentioning

confidence: 99%

Comparison of feeding suppression by the anorexigenic hormones neuromedin U and neuromedin S in rats

Nakahara

Katayama

Maruyama³

et al. 2010

Journal of Endocrinology

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We compared the central mechanisms of feeding suppression by the anorexigenic hormones neuromedin U (NMU) and neuromedin S (NMS) in rats. I.c.v. injection of either NMU or NMS dose dependently decreased 3-h food intake during the first quarter of a dark period. Pretreatment involving i.c.v. injection of a specific anti-NMS IgG blocked the suppression of food intake induced by i.c.v.-and i.p.-injected leptin, but anti-NMU IgG elicited no blockade. Quantitative PCR analysis revealed that i.c.v. injection of NMU or NMS caused a dose-dependent increase in CRH and proopiomelanocortin mRNA expression in the paraventricular nucleus (PVN) and arcuate nucleus (Arc) respectively. In tissue cultures of the Arc, secretion of a-melanocyte-stimulating hormone was stimulated by NMU and NMS, with more potent stimulation by NMS. The time-course curves of the increase in neuronal firing rate in Arc slices in response to NMU and NMS showed almost the same pattern, with a peak 10-15 min after treatment, whereas the time-course curves for the PVN slices differed between NMU and NMS. These results suggest that NMS and NMU may share anorexigenic effects, depending on physiological conditions.

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Pro-nociceptive effects of neuromedin u in rat

Cited by 53 publications

References 22 publications

Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia

Neuromedin U is regulated by the metastasis suppressor RhoGDI2 and is a novel promoter of tumor formation, lung metastasis and cancer cachexia

Neuromedin Elicits Cytokine Release in Murine Th2-Type T Cell Clone D10.G4.1

Comparison of feeding suppression by the anorexigenic hormones neuromedin U and neuromedin S in rats

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