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https://www.readbyqxmd.com/read/28916358/the-functional-characterization-and-comparison-of-two-single-crd-containing-c-type-lectins-with-novel-and-typical-key-motifs-from-portunus-trituberculatus
#1
Mengmeng Huang, Changkao Mu, Yuehong Wu, Fei Ye, Dan Wang, Cong Sun, Zhengbing Lv, Bingnan Han, Chunlin Wang, Xue-Wei Xu
C-type lectins are a superfamily of Ca(2+)-dependent carbohydrate-recognition proteins, which play crucial roles in innate immunity including nonself-recognition and pathogen elimination. In the present study, two single-CRD containing C-type lectins were identified from swimming crab Portunus trituberculatus (designated as PtCTL-2 and PtCTL-3). The open reading frame (ORF) of PtCTL-2 encoded polypeptides of 485 amino acids with a signal peptide and a single carbohydrate-recognition domain (CRD), while PtCTL-3's ORF encoded polypeptides of 241 amino acids with a coiled-coil region and a single-CRD...
September 12, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28912176/anexelekto-mer-tyrosine-kinase-inhibitor-ono-7475-growth-arrests-and-kills-fms-like-tyrosine-kinase-3-internal-tandem-duplication-mutant-acute-myeloid-leukemia-cells-by-diverse-mechanisms
#2
Peter P Ruvolo, Huaxian Ma, Vivian R Ruvolo, Xiaorui Zhang, Hong Mu, Wendy Schober, Ivonne Hernandez, Miguel Gallardo, Joseph Khoury, Jorge Cortes, Michael Andreeff, Sean M Post
Nearly one-third of patients with acute myeloid leukemia have FMS-Like Tyrosine Kinase 3 mutations and thus have poor survival prospects. Receptor tyrosine kinase Anexelekto is critical for FMS-Like Tyrosine Kinase 3 signaling and participates in FMS-Like Tyrosine Kinase 3 inhibitor resistance mechanisms. Thus, strategies targeting Anexelekto could prove useful for acute myeloid leukemia therapy. ONO-7475 is an inhibitor with high specificity for Anexelekto and MER Tyrosine Kinase. Here we report that ONO-7475 potently arrested growth and induced apoptosis in acute myeloid leukemia with internal tandem duplication mutation of FMS-Like Tyrosine Kinase 3...
September 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28902684/estrogens-synthesized-and-acting-within-a-spinal-oligomer-suppress-spinal-endomorphin-2-antinociception-ebb-and-flow-over-the-rat-reproductive-cycle
#3
Nai-Jiang Liu, Vijaya Murugaiyan, Emiliya M Storman, Stephen A Schnell, Martin W Wessendorf, Alan R Gintzler
The magnitude of antinociception elicited by intrathecal endomorphin 2 (EM2), an endogenous mu-opioid receptor (MOR) ligand, varies across the rat estrous cycle. We now report that phasic changes in analgesic responsiveness to spinal EM2 result from plastic interactions within a novel membrane-bound oligomer containing estrogen receptors (mERs), aromatase (aka estrogen synthase), metabotropic glutamate receptor 1 (mGluR1), and MOR. During diestrus, spinal mERs, activated by locally synthesized estrogens, act with mGluR1 to suppress spinal EM2/MOR antinociception...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28901488/the-role-of-fructose%C3%A2-1-6%C3%A2-bisphosphatase-1-in-abnormal-development-of-ovarian-follicles-caused-by-high-testosterone-concentration
#4
Tao Liu, Han Zhao, Jianfeng Wang, Xin Shu, Yuan Gao, Xiaoli Mu, Fei Gao, Hongbin Liu
The present study aimed to identify the molecular mechanisms underlying the effects of the fructose‑1,6‑bisphosphatase 1 (FBP1) signaling pathway within normal follicle development and in hyperandrogenism‑induced abnormal follicle growth. To achieve this, murine primary follicles, granulosa cells (GCs) and theca‑interstitial cells (TICs) were isolated, cultured in vitro and treated with a high concentration of androgens. A concentration of 1x10‑5 mol/l testosterone was considerable to induce hyperandrogenism by MTT assay...
September 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900035/prion-protein-is-required-for-tumor-necrosis-factor-alpha-tnf%C3%AE-triggered-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-signaling-and-cytokine-production
#5
Gui-Ru Wu, Tian-Chen Mu, Zhen-Xing Gao, Jun Wang, Man-Sun Sy, Chao-yang Li
The expression of normal cellular prion protein (PrP) is required for the pathogenesis of prion diseases. However, the physiological functions of PrP remain ambiguous. Here, we identified PrP as being critical for tumor necrosis factor (TNF)α-triggered signaling in a human melanoma cell line, M2, and a pancreatic ductal cell adenocarcinoma cell line, BxPC-3. In M2 cells, TNFα upregulates the expression of p-I-kappa-B-kinase α/β (p-IKKα/β), p-p65, and p-JNK, but downregulates the IκBα protein, all of which are downstream signaling intermediates in the TNF receptor signaling cascade...
September 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28891868/a-bivalent-ligand-that-activates-mu-opioid-receptor-and-antagonizes-mglur5-receptor-reduces-neuropathic-pain-in-mice
#6
Cristina D Peterson, Kelley F Kitto, Eyup Akgün, Mary M Lunzer, Maureen S Riedl, Lucy Vulchanova, George L Wilcox, Philip S Portoghese, Carolyn A Fairbanks
The mu opioid receptor (MOR) and metabotropic glutamate receptor 5 (mGluR5) are well-established pharmacological targets in the management of chronic pain. Both receptors are expressed in spinal cord. MMG22, a bivalent ligand containing two pharmacophores separated by 22 atoms that simultaneously activates MOR and antagonizes mGluR5 has been shown to produce potent reversal of tactile hypersensitivity in rodent models of LPS- and bone-cancer-induced chronic pain. The present study assessed whether intrathecal MMG22 also is effective in reducing pain of neuropathic origin...
September 1, 2017: Pain
https://www.readbyqxmd.com/read/28884835/non-invasive-electromyographic-estimation-of-motor-unit-number-in-the-external-anal-sphincter-of-the-rat
#7
Chuan Zhang, Alvaro Munoz, H Henry Lai, Timothy Boone, Yingchun Zhang
AIMS: The external anal sphincter (EAS) is essential for maintaining fecal continence. Neurological disorders or traumatic injuries to muscle and nervous systems could lead to EAS denervation. Currently, there are no techniques available to document global innervation changes in the EAS in vivo. The aim of this study was to develop a novel approach to non-invasively estimate the number of functioning motor units (MUs) in the EAS and validate with immunofluorescent techniques in rats. METHODS: Intra-rectal surface electromyography (EMG) signals of the EAS, induced by a series of intra-vaginally delivered pudendal nerve stimulations with different intensities, were recorded...
September 8, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28880247/the-actin-cytoskeleton-is-involved-in-glial-cell-line-derived-neurotrophic-factor-gdnf-induced-ret-translocation-into-lipid-rafts-in-dopaminergic-neuronal-cells
#8
Li Li, Haijing Song, Peipei Mu, Ming Xu, Chaoxia Liu, Ying Wang, Yingsong Qin, Shen Sun, Jin Gao, Ting Wang, Dianshuai Gao
Glial cell line-derived neurotrophic factor (GDNF), a potential therapeutic factor for Parkinson's disease (PD), exerts its biological effects through the Ret receptor tyrosine kinase. The redistribution of Ret into lipid rafts substantially influences Ret signaling, but the mechanisms underlying Ret translocation remain unclear. The purpose of our study was to further explore the signaling mechanisms of GDNF and to determine whether the actin cytoskeleton is involved in the GDNF-induced Ret translocation into lipid rafts...
September 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28880013/osimertinib-azd9291-decreases-programmed-death-ligand-1-in-egfr-mutated-non-small-cell-lung-cancer-cells
#9
Xiao-Ming Jiang, Yu-Lian Xu, Mu-Yang Huang, Le-Le Zhang, Min-Xia Su, Xiuping Chen, Jin-Jian Lu
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1). Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro. Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28879802/anti-nociceptive-interactions-between-opioids-and-a-cannabinoid-receptor-2-agonist-in-inflammatory-pain
#10
Matthew B Yuill, David E Hale, Josée Guindon, Daniel J Morgan
The cannabinoid 1 receptor and cannabinoid 2 receptor can both be targeted in the treatment of pain; yet, they have some important differences. Cannabinoid 1 receptor is expressed at high levels in the central nervous system, whereas cannabinoid 2 receptor is found predominantly, although not exclusively, outside the central nervous system. The objective of this study was to investigate potential interactions between cannabinoid 2 receptor and the mu-opioid receptor in pathological pain. The low level of adverse side effects and lack of tolerance for cannabinoid 2 receptor agonists are attractive pharmacotherapeutic traits...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28874583/smad7-enables-stat3-activation-and-promotes-pluripotency-independent-of-tgf-%C3%AE-signaling
#11
Yi Yu, Shuchen Gu, Wenjian Li, Chuang Sun, Fenfang Chen, Mu Xiao, Lei Wang, Dewei Xu, Ye Li, Chen Ding, Zongping Xia, Yi Li, Sheng Ye, Pinglong Xu, Bin Zhao, Jun Qin, Ye-Guang Chen, Xia Lin, Xin-Hua Feng
Smad7 is a negative feedback product of TGF-β superfamily signaling and fine tunes a plethora of pleiotropic responses induced by TGF-β ligands. However, its noncanonical functions independent of TGF-β signaling remain to be elucidated. Here, we show that Smad7 activates signal transducers and activators of transcription 3 (STAT3) signaling in maintaining mouse embryonic stem cell pluripotency in a manner independent of the TGF-β receptors, yet dependent on the leukemia inhibitory factor (LIF) coreceptor glycoprotein 130 (gp130)...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28871491/robust-age-but-limited-sex-differences-in-mu-opioid-receptors-in-the-rat-brain-relevance-for-reward-and-drug-seeking-behaviors-in-juveniles
#12
Caroline J W Smith, Aarane M Ratnaseelan, Alexa H Veenema
In the brain, the µ-opioid receptor (MOR) is involved in reward-seeking behaviors and plays a pivotal role in the mediation of opioid use disorders. Furthermore, reward-seeking behaviors and susceptibility to opioid addiction are particularly evident during the juvenile period, with a higher incidence of opioid use in males and higher sensitivity to opioids in females. Despite these age and sex differences in MOR-mediated behaviors, little is known regarding potential age and sex differences in the expression of MORs in the brain...
September 4, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28871199/morphine-induced-hyperalgesia-involves-mu-opioid-receptors-and-the-metabolite-morphine-3-glucuronide
#13
Laurie-Anne Roeckel, Valérie Utard, David Reiss, Jinane Mouheiche, Hervé Maurin, Anne Robé, Emilie Audouard, John N Wood, Yannick Goumon, Frédéric Simonin, Claire Gaveriaux-Ruff
Opiates are potent analgesics but their clinical use is limited by side effects including analgesic tolerance and opioid-induced hyperalgesia (OIH). The Opiates produce analgesia and other adverse effects through activation of the mu opioid receptor (MOR) encoded by the Oprm1 gene. However, MOR and morphine metabolism involvement in OIH have been little explored. Hence, we examined MOR contribution to OIH by comparing morphine-induced hyperalgesia in wild type (WT) and MOR knockout (KO) mice. We found that repeated morphine administration led to analgesic tolerance and hyperalgesia in WT mice but not in MOR KO mice...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28864212/14-o-methylmorphine-a-novel-selective-mu-opioid-receptor-agonist-with-high-efficacy-and-affinity
#14
Ferenc Zádor, Mihály Balogh, András Váradi, Zoltán S Zádori, Kornél Király, Edina Szűcs, Bence Varga, Bernadette Lázár, Sándor Hosztafi, Pál Riba, Sándor Benyhe, Susanna Fürst, Mahmoud Al-Khrasani
14-O-methyl (14-O-Me) group in morphine-6-O-sulfate (M6SU) or oxymorphone has been reported to be essential for enhanced affinity, potency and antinociceptive effect of these opioids. Herein we report on the pharmacological properties (potency, affinity and efficacy) of the new compound, 14-O-methylmorphine (14-O-MeM) in in vitro. Additionally, we also investigated the antinociceptive effect of the novel compound, as well as its inhibitory action on gastrointestinal transit in in vivo. The potency and efficacy of test compound were measured by [(35)S]GTPγS binding, isolated mouse vas deferens (MVD) and rat vas deferens (RVD) assays...
August 30, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28864209/danshensu-accelerates-angiogenesis-after-myocardial-infarction-in-rats-and-promotes-the-functions-of-endothelial-progenitor-cells-through-sdf-1%C3%AE-cxcr4-axis
#15
Ying Yin, Jialin Duan, Chao Guo, Guo Wei, Yanhua Wang, Yue Guan, Fei Mu, Minna Yao, Miaomiao Xi, Aidong Wen
The present study was performed to investigate the potential role of Danshensu in therapeutic angiogenesis in ischemic myocardium and endothelial progenitor cells (EPCs) function. The rat model of myocardial infarction (MI) injury was induced by left anterior descending coronary artery ligation for 14 days. Danshensu significantly alleviated myocardial ischemia injury by ameliorating left ventricular function and reducing infarct size. Furthermore, Danshensu potentiated post-ischemia neovascularization as evidenced by increased microvessel density in infarction boundary zone, as well as the expression of marker proteins vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF)...
August 31, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28863321/the-role-of-necroptosis-in-status-epilepticus-induced-brain-injury-in-juvenile-rats
#16
Qianyun Cai, Jing Gan, Rong Luo, Yi Qu, Shiping Li, Chaomin Wan, Dezhi Mu
PURPOSE: To study the role of necroptosis in status epilepticus (SE)-induced injury in the developing brain and the possible associations of necroptosis with epileptogenesis and cognitive dysfunction. METHODS: The lithium-pilocarpine epilepsy model was reproduced in male rats at postnatal day 25. Propidium iodide (PI) staining was used to detect cell death after SE. Transmission electron microscopy (TEM) was performed to observe morphological changes in injured neurons...
August 29, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28860501/in-vivo-immune-interactions-of-multipotent-stromal-cells-underlie-their-long-lasting-pain-relieving-effect
#17
Wei Guo, Satoshi Imai, Jia-Le Yang, Shiping Zou, Mineo Watanabe, Yu-Xia Chu, Zaid Mohammad, Huakun Xu, Kamal D Moudgil, Feng Wei, Ronald Dubner, Ke Ren
Systemic infusion of bone marrow stromal cells (BMSCs), a major type of multipotent stromal cells, produces pain relief (antihyperalgesia) that lasts for months. However, studies have shown that the majority of BMSCs are trapped in the lungs immediately after intravenous infusion and their survival time in the host is inconsistent with their lengthy antihyperalgesia. Here we show that long-lasting antihyperalgesia produced by BMSCs required their chemotactic factors such as CCL4 and CCR2, the integrations with the monocytes/macrophages population, and BMSC-induced monocyte CXCL1...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28859285/bovine-lineage-specification-revealed-by-single-cell-gene-expression-analysis-from-zygote-to-blastocyst
#18
Qingqing Wei, Liang Zhong, Shaopeng Zhang, Haiyuan Mu, Jinzhu Xiang, Liang Yue, Yunping Dai, Jianyong Han
Preimplantation embryos undergo zygotic genome activation and lineage specification resulting in three distinct cell types in the late blastocyst. The molecular mechanisms underlying this progress are largely unknown in bovines. Here, we sought to analyze an extensive set of regulators at the single-cell level to define the events involved in the development of the bovine blastocyst. Using a quantitative microfluidics approach in single cells, we analyzed mRNA levels of 96 genes known to function in early embryonic development and maintenance of stem cell pluripotency in parallel in 384 individual cells from bovine preimplantation embryos...
July 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28858018/naloxegol-for-managing-opioid-induced-constipation
#19
Krystal N Shelton, Jennifer N Clements
Naloxegol is a peripherally acting mu-opioid receptor antagonist for opioid-induced constipation in adults with chronic noncancer pain. This drug's once-daily oral formulation can be used as monotherapy and helps to decrease the constipating effects of opioid therapy; however, it has been associated with abdominal pain.
September 2017: JAAPA: Official Journal of the American Academy of Physician Assistants
https://www.readbyqxmd.com/read/28855588/morphine-activation-of-mu-opioid-receptors-causes-disinhibition-of-neurons-in-the-ventral-tegmental-area-mediated-by-%C3%AE-arrestin2-and-c-src
#20
Fiona A Bull, Daniel T Baptista-Hon, Jeremy J Lambert, Wendy Walwyn, Tim G Hales
The tyrosine kinase, c-Src, participates in mu opioid receptor (MOP) mediated inhibition in sensory neurons in which β-arrestin2 (β-arr2) is implicated in its recruitment. Mice lacking β-arr2 exhibit increased sensitivity to morphine reinforcement; however, whether β-arr2 and/or c-Src participate in the actions of opioids in neurons within the reward pathway is unknown. It is also unclear whether morphine acts exclusively through MOPs, or involves delta opioid receptors (DOPs). We examined the involvement of MOPs, DOPs, β-arr2 and c-Src in the inhibition by morphine of GABAergic inhibitory postsynaptic currents (IPSCs) recorded from neurons in the mouse ventral tegmental area...
August 30, 2017: Scientific Reports
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