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https://www.readbyqxmd.com/read/29035280/adipocyte-cannabinoid-receptor-cb1-regulates-energy-homeostasis-and-alternatively-activated-macrophages
#1
Inigo Ruiz de Azua, Giacomo Mancini, Raj Kamal Srivastava, Alejandro Aparisi Rey, Pierre Cardinal, Laura Tedesco, Cristina Maria Zingaretti, Antonia Sassmann, Carmelo Quarta, Claudia Schwitter, Andrea Conrad, Nina Wettschureck, V Kiran Vemuri, Alexandros Makriyannis, Jens Hartwig, Maria Mendez-Lago, Laura Bindila, Krisztina Monory, Antonio Giordano, Saverio Cinti, Giovanni Marsicano, Stefan Offermanns, Enzo Nisoli, Uberto Pagotto, Daniela Cota, Beat Lutz
Dysregulated adipocyte physiology leads to imbalanced energy storage, obesity, and associated diseases, imposing a costly burden on current health care. Cannabinoid receptor type-1 (CB1) plays a crucial role in controlling energy metabolism through central and peripheral mechanisms. In this work, adipocyte-specific inducible deletion of the CB1 gene (Ati-CB1-KO) was sufficient to protect adult mice from diet-induced obesity and associated metabolic alterations and to reverse the phenotype in already obese mice...
October 16, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29035279/cannabis-in-fat-high-hopes-to-treat-obesity
#2
Melody N Hawkins, Tamas L Horvath
Cannabinoid receptor type-1 (CB1s) is known to have a substantial impact on the regulation of energy metabolism via central and peripheral mechanisms. In this issue of the JCI, Ruiz de Azua and colleagues provide important insights into the regulation of adipocyte physiology by CB1. Mice with adipocyte-specific deletion of the CB1-encoding gene had an overall improved metabolic profile in addition to reduced body weight and total adiposity. These changes were associated with an increase in sympathetic tone of the adipose tissue and expansion of activated macrophages, both of which occurred prior to changes in body weight, lending support to a causal relationship between loss of CB1 in adipocytes and systemic metabolic changes...
October 16, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29033935/cannabinoid-receptor-1-participates-in-liver-inflammation-by-promoting-m1-macrophage-polarization-via-rhoa-nf-%C3%AE%C2%BAb-p65-and-erk1-2-pathways-respectively-in-mouse-liver-fibrogenesis
#3
Lei Tian, Weiyang Li, Le Yang, Na Chang, Xiaoting Fan, Xiaofang Ji, Jieshi Xie, Lin Yang, Liying Li
Macrophage M1/M2 polarization mediates tissue damage and inflammatory responses. Cannabinoid receptor (CB) 1 participated in liver fibrogenesis by affecting bone marrow (BM)-derived monocytes/macrophages (BMMs) activation. However, the knowledge of whether CB1 is involved in the polarization of BMMs remains limited. Here, we found M1 gene signatures (including CD86, MIP-1β, tumor necrosis factor, IL-6, and inducible nitric oxide synthase) and the amount of M1 macrophages (CD86(+) cells, gated by F4/80) were significantly elevated in carbon tetrachloride (CCl4)-induced mouse injured livers, while that of M2 type macrophages had little change by RT-qPCR and fluorescence-activated cell sorting (FACS)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033903/protective-effect-of-akkermansia-muciniphila-against-immune-mediated-liver-injury-in-a-mouse-model
#4
Wenrui Wu, Longxian Lv, Ding Shi, Jianzhong Ye, Daiqiong Fang, Feifei Guo, Yating Li, Xingkang He, Lanjuan Li
Accumulating evidence indicates that gut microbiota participates in the pathogenesis and progression of liver diseases. The severity of immune-mediated liver injury is associated with different microbial communities. Akkermansia muciniphila can regulate immunologic and metabolic functions. However, little is known about its effects on gut microbiota structure and function. This study investigated the effect of A. muciniphila on immune-mediated liver injury and potential underlying mechanisms. Twenty-two C57BL/6 mice were assigned to three groups (N = 7-8 per group) and continuously administrated A...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29032058/cross-state-dependency-of-learning-between-arachidonylcyclopropylamide-acpa-and-muscimol-in-the-mouse-dorsal-hippocampus
#5
Majid Jafari-Sabet, Amir-Mohammad Karimi
The aim of the present study was to examine cross state-dependent learning between ACPA (a selective cannabinoid CB1 receptor agonist) and muscimol (a selective GABAA receptor agonist) in the step-down inhibitory avoidance learning task. The dorsal hippocampal CA1 regions of adult male NMRI mice were bilaterally cannulated, and all drugs were microinjected into the intended sites of injection. Post-training and/or pre-test administration of ACPA (1 and 2ng/mouse) dose-dependently induced amnesia. Pre-test microinjection of the same doses of ACPA reversed the post-training ACPA-induced amnesia...
October 12, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29031837/impaired-contrast-sensitivity-at-low-spatial-frequency-in-cannabis-users-with-early-onset
#6
Laurence Lalanne, Eglantine Ferrand-Devouge, Sebastien Kirchherr, Lucie Rauch, Estelle Koning, Claude Speeg, Vincent Laprevote, Anne Giersch
The regular use of cannabis generates pronounced cognitive disorders, especially in users who begin before the age of 15-16. However, less is known about the impact of regular cannabis on visual function, especially in the case of early onset. Cannabinoid receptors (CB1) are expressed in areas of the visual system, like the thalamus and primary cortex, which might originate sensory disorders. Hence, we measured contrast sensitivity (CS) in three groups, i.e. cannabis users with late onset of cannabis use (after 16 years old), cannabis users with early onset"...
October 11, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29031713/peripheral-cannabinoid-1-receptor-blockade-restores-hypothalamic-leptin-signaling
#7
Joseph Tam, Gergő Szanda, Adi Drori, Ziyi Liu, Resat Cinar, Yoshihiro Kashiwaya, Marc L Reitman, George Kunos
OBJECTIVE: In visceral obesity, an overactive endocannabinoid/CB1 receptor (CB1R) system promotes increased caloric intake and decreases energy expenditure, which are mitigated by global or peripheral CB1R blockade. In mice with diet-induced obesity (DIO), inhibition of food intake by the peripherally restricted CB1R antagonist JD5037 could be attributed to endogenous leptin due to the rapid reversal of hyperleptinemia that maintains leptin resistance, but the signaling pathway engaged by leptin has remained to be determined...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29031708/the-brain-strikes-back-hypothalamic-targets-for-peripheral-cb1-receptor-inverse-agonism
#8
Daniela Cota
No abstract text is available yet for this article.
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29030083/human-bone-marrow-mesenchymal-stem-cells-secrete-endocannabinoids-that-stimulate-in-vitro-hematopoietic-stem-cell-migration-effectively-comparable-to-beta-adrenergic-stimulation
#9
Sevil Köse, Fatima Aerts-Kaya, Ağla Zübeyde Köprü, Emirhan Nemutlu, Barış Kuşkonmaz, Beren Karaosmanoğlu, Zihni Ekim Taşkıran, Belgin Altun, Duygu Uçkan Çetinkaya, Petek Korkusuz
Granulocyte Colony-Stimulating Factor (G-CSF) is a well-known hematopoietic stem cell (HSC) mobilizing agent used in both allogeneic and autologous transplantation. However, a proportion of patients or healthy donors fail to mobilize sufficient number of cells. New mobilization agents are therefore needed. Endocannabinoids (eCBs) are endogenous lipid mediators generated in the brain and peripheral tissues and activate the cannabinoid receptors (CB1, CB2). We suggest that eCBs may act as mobilizers of hematopoietic stem cells (HSC) from the BM under stress conditions as beta adrenergic receptors (Adrβ)...
October 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29017758/in-vitro-and-in-vivo-pharmacological-characterization-of-asp8477-a-novel-highly-selective-fatty-acid-amide-hydrolase-inhibitor
#10
Tomonari Watabiki, Noriko Tsuji, Tetsuo Kiso, Tohru Ozawa, Fumie Narazaki, Shuichiro Kakimoto
Although exogenous agonists for cannabinoid (CB) receptors are clinically effective for treating chronic pain, global activation of brain CB receptors causes frequent central nervous system (CNS) side-effects. Fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme for anandamide (AEA), an endogenous CB. Recently, we discovered a novel FAAH inhibitor, 3-pyridyl 4-(phenylcarbamoyl)piperidine-1-carboxylate (ASP8477). In vitro studies demonstrated that ASP8477 inhibited human FAAH-1, FAAH-1 (P129T) and FAAH-2 activity with IC50 values of 3...
October 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29016748/the-second-generation-cryoballoon-has-improved-durable-isolation-of-left-but-not-right-pulmonary-veins-new-insights-from-a-multicentre-study
#11
Raphaël P Martins, Vincent Galand, Olivier Cesari, Antoine Milhem, Nathalie Behar, Vincent Auffret, Jean-Claude Daubert, Philippe Mabo, Dominique Pavin
Aims: Pulmonary vein isolation (PVI) using second-generation cryoballoon (CB2) is associated with improved outcomes compared with first generation (CB1). We aimed at investigating the characteristics of left and right PV reconnections after CB1 and CB2 ablations in patients with clinical recurrences requiring redo ablation. Methods and results: From 2010 to 2016, 776 patients underwent 28-mm cryoballoon PVI for symptomatic paroxysmal atrial fibrillation (AF) in 3 centres, 279 with CB1 and 497 with CB2...
July 12, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28980210/photobiomodulation-therapy-improves-acute-inflammatory-response-in-mice-the-role-of-cannabinoid-receptors-atp-sensitive-k-channel-p38-mapk-signalling-pathway
#12
Laís M S Neves, Elaine C D Gonçalves, Juliana Cavalli, Graziela Vieira, Larissa R Laurindo, Róli R Simões, Igor S Coelho, Adair R S Santos, Alexandre M Marcolino, Maíra Cola, Rafael C Dutra
Although photobiomodulation therapy (PBM) has been applied clinically for the treatment of pain and inflammation, wound healing, sports and soft tissue injuries, as well as to repair injured spinal cords and peripheral nerves, it remains unclear which molecular substrates (receptor) are implicated in the cellular mechanisms of PBM. Here, we reported that PBM (660 nm, 30 mW, 0.06 cm(2), 50 J/cm(2), plantar irradiation) significantly inhibited carrageenan-induced paw oedema, but not noxious thermal response, through positive modulation to both CB1 and CB2 cannabinoid receptors...
October 4, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28979317/the-role-of-bk-channels-in-antiseizure-action-of-the-cb1-receptor-agonist-acea-in-maximal-electroshock-and-pentylenetetrazole-models-of-seizure-in-mice
#13
Sina Asaadi, Mohammad Jahanbakhshi, Mahmoud Lotfinia, Nima Naderi
The anticonvulsant effect of cannabinoid compound has been shown in various models of seizure. On the other hand, there are controversial findings about the role of large conductance calcium-activated potassium (BK) channels in the pathogenesis of epilepsy. Also, there is no data regarding the effect of co-administration of cannabinoid type 1 (CB1) receptor agonists and BK channels antagonists in the acute models of seizure in mice. In this study, the effect of arachidonyl-2'-chloroethylamide (ACEA), a CB1 receptor agonist, and a BK channel antagonist, paxilline, either alone or in combination was investigated...
2017: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/28975684/salvinorin-a-reduces-neuropathic-nociception-in-the-insular-cortex-of-the-rat
#14
U Coffeen, A Canseco-Alba, K Simón-Arceo, A Almanza, F Mercado, M León-Olea, F Pellicer
BACKGROUND: Neuropathic pain is one of the most important challenges in public health. The search for novel treatments is important for an adequate relief without adverse effects. In this sense salvinorin A (SA), the main diterpene of the medicinal plant Salvia divinorum is an important antinociceptive compound, which acts as a potent agonist of kappa opioid receptor (KOR) and cannabinoid CB1 receptors. METHODS: We evaluated nociceptive responses in a neuropathic pain model induced by the sciatic nerve ligature (SNL) in the right hind paw, after the microinjection of SA, Salvinorin B (SB), KOR and CB1 antagonists directly in the insular cortex (IC) in male wistar rats...
October 4, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28972119/loss-of-fatty-acid-binding-protein-1-alters-the-hepatic-endocannabinoid-system-response-to-a-high-fat-diet
#15
Gregory G Martin, Danilo Landrock, Sarah Chung, Lawrence J Dangott, Avery L McIntosh, John T Mackie, Ann B Kier, Friedhelm Schroeder
Upregulation of hepatic endocannabinoid receptor (CB1) and arachidonoylethanolamide (AEA) is associated with non-alcoholic fatty liver disease (NAFLD). Male mice fed high fat diet (HFD) ad libitum also exhibit NAFLD, increased hepatic AEA, and obesity. But, preference for HFD complicates interpretation and almost nothing is known about these effects in females. These issues were addressed by pair-feeding HFD. Similarly to ad libitum fed HFD, pair-fed HFD also increased WT male and female mouse fat tissue mass (FTM), but preferentially at the expense of lean tissue mass (LTM)...
October 2, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28967368/is-cannabis-an-effective-treatment-for-joint-pain
#16
REVIEW
Richard J Miller, Rachel E Miller
Cannabis has been used to treat pain for thousands of years. However, since the early part of the 20th century, laws restricting cannabis use have limited its evaluation using modern scientific criteria. Over the last decade, the situation has started to change because of the increased availability of cannabis in the United States for either medical or recreational purposes, making it important to provide the public with accurate information as to the effectiveness of the drug for joint pain among other indications...
September 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28966975/nongenomic-glucocorticoid-suppression-of-a-postsynaptic-potassium-current-via-emergent-autocrine-endocannabinoid-signaling-in-hypothalamic-neuroendocrine-cells-following-chronic-dehydration
#17
Ning Wu, Jeffrey G Tasker
Glucocorticoids rapidly stimulate endocannabinoid synthesis and modulation of synaptic transmission in hypothalamic neuroendocrine cells via a nongenomic signaling mechanism. The endocannabinoid actions are synapse-constrained by astrocyte restriction of extracellular spatial domains. Exogenous cannabinoids have been shown to modulate postsynaptic potassium currents, including the A-type potassium current (IA), in different cell types. The activity of magnocellular neuroendocrine cells is shaped by a prominent IA...
September 2017: ENeuro
https://www.readbyqxmd.com/read/28963716/the-monoacylglycerol-lipase-inhibitor-kml29-with-gabapentin-synergistically-produces-analgesia-in-mice
#18
Molly S Crowe, Catheryn D Wilson, Emma Leishman, Paul L Prather, Heather B Bradshaw, Matthew L Banks, Steven G Kinsey
BACKGROUND AND PURPOSE: Gabapentin (GBP) is commonly prescribed for nerve pain but may also cause dizziness, sedation, and gait disturbances. Similarly, inhibition of the endogenous cannabinoid enzyme monoacylglycerol lipase (MAGL) has antinociceptive and anti-inflammatory properties, but also induces sedation in mice at high doses. To limit these side effects, the present study investigated the analgesic effects of coadministering a MAGL inhibitor with GBP. EXPERIMENTAL APPROACH: Mice subjected to the chronic constriction injury (CCI) model of neuropathic pain were administered the MAGL inhibitor KML29 (1-40 mg kg(-1) , i...
September 29, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28955964/effect-of-n-arachidonoyl-l-serine-on-human-cerebromicrovascular-endothelium
#19
Tomoyuki Kino, Toshiki Tomori, Rania Abutarboush, Paola Castri, Ye Chen, Frederick A Lenz, Richard M McCarron, Maria Spatz
N-arachidonoyl-l-serine (ARA-S) is an endogenous lipid, chemically related to the endocannabinoid, N-arachidonoyl ethanolamine (i.e., anandamide) and with similar physiologic and pathophysiologic functions. Reports indicate that ARA-S possesses vasoactive and neuroprotective properties resembling those of cannabinoids. However, in contrast to cannabinoids, ARA-S binds weakly to its known classical receptors, CB1 and CB2, and is therefore considered to be a 'cannabinoid-like' substance. The originally described ARA-S induced-endothelial-dependent vasorelaxation was not abrogated by CB1, CB2 receptor antagonists or TRPV1 competitive inhibitor...
December 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28954820/cannabidiol-and-palmitoylethanolamide-are-anti-inflammatory-in-the-acutely-inflamed-human-colon
#20
Daniel G Couch, Chris Tasker, Elena Theophilidou, Jonathan N Lund, Saoirse E O'Sullivan
Objective: We sought to quantify the anti-inflammatory effects of two cannabinoid drugs: cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue.  These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants. Design: Caco-2 cells and human colonic explants collected from elective bowel cancer, inflammatory bowel disease (IBD) or acute appendicitis resections, and were treated with the following drug treatments: vehicle, an inflammatory protocol of IFNγ and TNFα (10 ng/ml), inflammation and PEA (10µM), inflammation and CBD (10µM), & PEA or CBD alone...
September 27, 2017: Clinical Science (1979-)
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