Read by QxMD icon Read

Sigma receptor

Francesco Spinelli, Ahmed Haider, Annamaria Toscano, Maria Laura Pati, Claudia Keller, Francesco Berardi, Nicola Antonio Colabufo, Carmen Abate, Simon M Ametamey
The Sigma-1 receptor (Sig-1R) has been described as a pluripotent modulator of distinct physiological functions and its involvement in various central and peripheral pathological disorders has been demonstrated. However, further investigations are required to understand the complex role of the Sig-1R as a molecular chaperon. A specific PET radioligand would provide a powerful tool in Sig-1R related studies. As part of our efforts to develop a Sig-1R PET radioligand that shows antagonistic properties, we investigated the suitability of 1-(4-(6-methoxynaphthalen-1-yl)butyl)-4-methylpiperidine (designated PB212) for imaging Sig-1R...
2018: American Journal of Nuclear Medicine and Molecular Imaging
Sílvia Castany, Georgia Gris, José Miguel Vela, Enrique Verdú, Pere Boadas-Vaello
Sigma-1 receptor (σ1 R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice after spinal cord contusion injury (SCI) - a model of central neuropathic pain. The modulatory effect of σ1 R KO on extracellular mediators and signalling pathways in the spinal cord was also investigated. In particular, changes in the expression of inflammatory cytokines (tumour necrosis factor TNF-α, interleukin IL-1β) and both the expression and activation (phosphorylation) of the N-methyl-D-aspartate receptor subunit 2B (NR2B-NMDA) and extracellular signal-regulated kinases (ERK1/2) were analysed...
March 1, 2018: Scientific Reports
Fiona Henderson, Philippa J Hart, Jesus M Pradillo, Michael Kassiou, Lidan Christie, Kaye J Williams, Herve Boutin, Adam McMahon
RATIONALE: Stroke is a leading cause of disability worldwide. Understanding the recovery process post-stroke is essential; however, longer-term recovery studies are lacking. In-vivo Positron emission tomography (PET) can image biological recovery processes, but is limited by spatial resolution and its targeted nature. Untargeted mass spectrometry imaging offers high spatial resolution, providing an ideal ex-vivo tool for brain recovery imaging. METHODS: Magnetic resonance imaging (MRI) was used to image a rat brain 48 hours after ischaemic stroke to locate the infarcted regions of the brain...
February 27, 2018: Rapid Communications in Mass Spectrometry: RCM
David Aguinaga, Mireia Medrano, Ignacio Vega-Quiroga, Katia Gysling, Enric I Canela, Gemma Navarro, Rafael Franco
Sigma σ1 and σ2 receptors are targets of cocaine. Despite sharing a similar name, the two receptors are structurally unrelated and their physiological role is unknown. Cocaine increases the level of dopamine, a key neurotransmitter in CNS motor control and reward areas. While the drug also affects dopaminergic signaling by allosteric modulations exerted by σ1 R interacting with dopamine D1 and D2 receptors, the potential regulation of dopaminergic transmission by σ2 R is also unknown. We here demonstrate that σ2 R may form heteroreceptor complexes with D1 but not with D2 receptors...
2018: Frontiers in Molecular Neuroscience
Qi-Jun Gao, Bo Yang, Jing Chen, Shao-Bo Shi, Hong-Jie Yang, Xin Liu
Background: The sigma receptors are a relatively novel receptor group with respect to knowledge of their effect on health. Although the sigma-1 receptor agonist PRE-084 exhibits a cardioprotective effect in some studies, the benefits in cases of myocardial ischemia/reperfusion (I/R) are not clear. The aim of this study was to explore the mechanism of action and assess the effect of PRE-084 on myocardial I/R injury in rats. Methods: In this study, rats were assigned randomly to three groups with computer (n = 14 for each group): a sham group, an I/R group, and a PRE-084 group...
March 5, 2018: Chinese Medical Journal
Caroline M Gorvin, Angela Rogers, Michelle Stewart, Anju Paudyal, Tertius A Hough, Lydia Teboul, Sara Wells, Steve Dm Brown, Roger D Cox, Rajesh V Thakker
The adaptor protein-2 sigma subunit (AP2σ), encoded by AP2S1 , forms a heterotetrameric complex, with AP2α, AP2β, and AP2μ subunits, that is pivotal for clathrin-mediated endocytosis, and AP2σ loss-of-function mutations impair internalization of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor, and cause familial hypocalciuric hypercalcemia type-3 (FHH3). Mice with AP2σ mutations that would facilitate investigations of the in vivo role of AP2σ, are not available, and we therefore embarked on establishing such mice...
May 2, 2017: JBMR Plus
Miguel Á Tejada, Ángeles Montilla-García, Rafael González-Cano, Inmaculada Bravo-Caparrós, M Carmen Ruiz-Cantero, Francisco R Nieto, Enrique J Cobos
Immune cells have a known role in pronociception, since they release a myriad of inflammatory algogens which interact with neurons to facilitate pain signaling. However, these cells also produce endogenous opioid peptides with analgesic potential. The sigma-1 receptor is a ligand-operated chaperone that modulates neurotransmission by interacting with multiple protein partners, including the μ-opioid receptor. We recently found that sigma-1 antagonists are able to induce opioid analgesia by enhancing the action of endogenous opioid peptides of immune origin during inflammation...
February 15, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Yu-Tong Sun, Gui-Fei Wang, Yi-Qiu Yang, Fujun Jin, Yifei Wang, Xiao-Yang Xie, Robert H Mach, Yun-Sheng Huang
Increasing evidences have implicated that sigma-2 receptor is a biomarker and significantly over-expressed in many proliferative cancer cells with no or low expression in normal cells. Sigma-2 receptor selective ligands have been successfully used as valuable tools to study its pharmacological functions, tumor imaging, and cancer therapeutics or adjuvants. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolinylalkyl benzamides are among a few categories of structures that have demonstrated high affinities and selectivities for sigma-2 receptor and been used extensively as study tools in various tumor imaging and therapy...
November 9, 2017: European Journal of Medicinal Chemistry
Sudip Mondal, Evan Hegarty, James J Sahn, Luisa L Scott, Sertan K Gökçe, Christopher Martin, Navid Ghorashian, Praveen Navoda Satarasinghe, Sangeetha Iyer, Wisath Sae-Lee, Timothy Hodges, Jonathan T Pierce, Stephen F Martin, Adela Ben-Yakar
The nematode Caenorhabditis elegans, with tractable genetics and a well-defined nervous system, provides a unique whole-animal model system to identify novel drug targets and therapies for neurodegenerative diseases. Large-scale drug or target screens in models that recapitulate the subtle age- and cell-specific aspects of neurodegenerative diseases are limited by a technological requirement for high-throughput analysis of neuronal morphology. Recently we developed a model of amyloid precursor protein-induced neurodegeneration that exhibits progressive degeneration of select cholinergic neurons...
February 9, 2018: ACS Chemical Neuroscience
Jiahong Qin, Peng Wang, Yi Li, Lan Yao, Yuanshan Liu, Tao Yu, Jiali Lin, Xiangshao Fang, Zitong Huang
BACKGROUND: Global cerebral ischemic/reperfusion (I/R) injury after cardiac arrest (CA) is a major cause of mortality and morbidity in survivors of resuscitation. We utilized a rat model of asphyxia CA to explore the functional effects and mechanisms of Sigma-1 receptor (Sig-1R) activation in cerebral protection using the Sig-1R agonist cutamesine (SA-4503). METHODS: After resuscitation, the surviving rats were randomly divided into three groups (n = 18 each): (1) the CPR group (0...
February 8, 2018: Shock
Xiaolei Wang, Chang Feng, Yong Qiao, Xin Zhao
No study has been conducted to examine the interactions of sigma-1 receptor (Sigma-1R) and high mobility group box 1 protein (HMGB1) in the development of diabetic peripheral neuropathy. Thus, we examined the effects of streptozotocin (STZ) treatment on expression of HMGB1 in subcellular levels in the dorsal root ganglion (DRG) in both wild-type and Sigma-1R-/- mice and evaluated the effects of repeated intrathecal administrations of selective Sigma-1R antagonists BD1047, agonist PRE-084, or HMGB1 inhibitor glycyrrhizin on peripheral neuropathy in wild-type mice...
February 5, 2018: Neuroscience Letters
Kouki Tadai, Tatsumasa Shioiri, Jun Tsuchimoto, Naoko Nagai, Hideto Watanabe, Nobuo Sugiura
Receptor type of protein tyrosine phosphatase sigma (RPTPσ) functions as a glycosaminoglycan (GAG) receptor of neuronal cells in both the central and peripheral nervous systems. Both chondroitin sulfate (CS) and heparan sulfate (HS) are important constituents of GAG ligands for RPTPσ, although they have opposite effects on neuronal cells. CS inhibits neurite outgrowth and neural regeneration through RPTPσ, whereas HS enhances them. We prepared recombinant RPTPσ N-terminal fragment containing the GAG binding site and various types of biotin-conjugated GAG (CS and HS) with chemical modification and chemo-enzymatic synthesis...
February 6, 2018: Journal of Biochemistry
Hideaki Yano, Alessandro Bonifazi, Min Xu, Daryl A Guthrie, Stephanie N Schneck, Ara M Abramyan, Andrew D Fant, W Conrad Hong, Amy H Newman, Lei Shi
The sigma 1 receptor (σ1R) is a structurally unique transmembrane protein that functions as a molecular chaperone in the endoplasmic reticulum (ER), and has been implicated in cancer, neuropathic pain, and psychostimulant abuse. Despite physiological and pharmacological significance, mechanistic underpinnings of structure-function relationships of σ1R are poorly understood, and molecular interactions of selective ligands with σ1R have not been elucidated. The recent crystallographic determination of σ1R as a homo-trimer provides the foundation for mechanistic elucidation at the molecular level...
January 30, 2018: Neuropharmacology
Qingxia Xu, Liang Li, Cuihong Han, Li Wei, Lingling Kong, Fanzhong Lin
Sigma-1 receptor (σ1R), an important transmembrane structural protein, has been demonstrated to be overexpressed in various types of human cancer, and has been confirmed to be involved in many biological behaviors during tumorigenesis and tumor progression. The aim of the present study was to explore the essential role of σ1R in hepatic malignant tumors (HMTs), which, to the best of our knowledge, has not been reported to date. We assessed σ1R expression in hepatocellular carcinoma (HCC) tissues and found that σ1R was significantly decreased in HCC when compared with that in benign liver tissues (P<0...
January 22, 2018: Oncology Reports
Miguel Ortíz-Rentería, Rebeca Juárez-Contreras, Ricardo González-Ramírez, León D Islas, Félix Sierra-Ramírez, Itzel Llorente, Sidney A Simon, Marcia Hiriart, Tamara Rosenbaum, Sara L Morales-Lázaro
The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in nociceptors where, when activated by chemical or thermal stimuli, it functions as an important transducer of painful and itch-related stimuli. Although the interaction of TRPV1 with proteins that regulate its function has been previously explored, their modulation by chaperones has not been elucidated, as is the case for other mammalian TRP channels. Here we show that TRPV1 physically interacts with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an antagonist of Sig-1R and an important neurosteroid associated to the modulation of pain...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Danielle O Sambo, Joseph J Lebowitz, Habibeh Khoshbouei
Methamphetamine (METH) abuse is a major public health issue around the world, yet there are currently no effective pharmacotherapies for the treatment of METH addiction. METH is a potent psychostimulant that increases extracellular dopamine levels by targeting the dopamine transporter (DAT) and alters neuronal activity in the reward centers of the brain. One promising therapeutic target for the treatment of METH addiction is the sigma-1 receptor (σ1R). The σ1R is an endoplasmic reticulum-localized chaperone protein that is activated by cellular stress, and, unique to this chaperone, its function can also be induced or inhibited by different ligands...
January 22, 2018: Pharmacology & Therapeutics
Caroline M Gorvin, Raghu Metpally, Victoria J Stokes, Fadil M Hannan, Sarath B Krishnamurthy, John D Overton, Jeffrey G Reid, Gerda E Breitwieser, Rajesh V Thakker
Mutations of the sigma subunit of the heterotetrameric adaptor-related protein complex 2 (AP2σ) impair signalling of the calcium-sensing receptor (CaSR), and cause familial hypocalciuric hypercalcaemia type 3 (FHH3). To date, FHH3-associated AP2σ mutations have only been identified at one residue, Arg15. We hypothesized that additional rare AP2σ variants may also be associated with altered CaSR function and hypercalcaemia, and sought for these by analysing >111,995 exomes (>60,706 from ExAc and dbSNP, and 51,289 from the Geisinger Health System-Regeneron DiscovEHR dataset which also contains clinical data)...
January 9, 2018: Human Molecular Genetics
Jingying Zhu, Songsong Zang, Xufeng Chen, Lei Jiang, Aihua Gu, Jie Cheng, Li Zhang, Jun Wang, Hang Xiao
Methamphetamine (Meth) is an illicit psychostimulant with high abuse potential and severe neurotoxicity. Recent studies have shown that dysfunctions in learning and memory induced by Meth may partially reveal the mechanisms of neuronal channelopathies. Kv2.1, the primary delayed rectifying potassium channel in neurons, is responsible for mediating apoptotic current surge. However, whether Kv2.1 is involved in Meth-mediated neural injury remains unknown. In the present study, the treatment of primary cultured hippocampal neurons with Meth indicated that Meth induced a time- and dose-dependent augmentation of Kv2...
January 3, 2018: Journal of Applied Toxicology: JAT
Hélène Hall, M Florencia Iulita, Palma Gubert, Lisi Flores Aguilar, Adriana Ducatenzeiler, Abraham Fisher, A Claudio Cuello
INTRODUCTION: AF710B (aka ANAVEX 3-71) is a novel selective allosteric M1 muscarinic and sigma-1 receptor agonist. In 3×Tg-AD mice, AF710B attenuates cognitive deficits and decreases Alzheimer-like hallmarks. We now report on the long-lasting disease-modifying properties of AF710B in McGill-R-Thy1-APP transgenic (Tg) rats. METHODS: Chronic treatment with AF710B (10 μg/kg) was initiated in postplaque 13-month-old Tg rats. Drug or vehicle was administered orally daily for 4...
December 29, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
Hoon-Seong Choi, Mi-Ji Lee, Sheu-Ran Choi, Branden A Smeester, Alvin J Beitz, Jang-Hern Lee
Aromatase is a key enzyme responsible for the biosynthesis of estrogen from testosterone. Although recent evidence indicates that spinal cord aromatase participates in nociceptive processing, the mechanisms underlying its regulation and its involvement in nociception remain unclear. The present study focuses on the potential role of astrocyte aromatase in formalin-induced acute pain and begins to uncover one mechanism by which spinal aromatase activation is controlled. Following intraplantar formalin injection, nociceptive responses were quantified and immunohistochemistry/co-immunoprecipitation assays were used to investigate the changes in spinal Fos expression and the phospho-serine levels of spinal aromatase...
December 28, 2017: Neuroscience
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"