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https://www.readbyqxmd.com/read/29331500/peripheral-modulation-of-the-endocannabinoid-system-in-metabolic-disease
#1
REVIEW
Nirajan Shrestha, James S M Cuffe, Dana S Hutchinson, John P Headrick, Anthony V Perkins, Andrew J McAinch, Deanne H Hryciw
Dysfunction of the endocannabinoid system (ECS) has been identified in metabolic disease. Cannabinoid receptor 1 (CB1) is abundantly expressed in the brain but also expressed in the periphery. Cannabinoid receptor 2 (CB2) is more abundant in the periphery, including the immune cells. In obesity, global antagonism of overexpressed CB1 reduces bodyweight but leads to centrally mediated adverse psychological outcomes. Emerging research in isolated cultured cells or tissues has demonstrated that targeting the endocannabinoid system in the periphery alleviates the pathologies associated with metabolic disease...
January 10, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29330286/agonist-induced-cxcr4-and-cb2-heterodimerization-inhibits-g%C3%AE-13-rhoa-mediated-migration
#2
Kisha A Scarlett, ElShaddai Z White, Christopher J Coke, Jada R Carter, Latoya K Bryant, Cimona V Hinton
G-protein coupled receptor (GPCR) heterodimerization has emerged as a means by which alternative signaling entities can be created; yet, how receptor heterodimers affect receptor pharmacology remains unknown. Previous observations suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically non-functional heterodimer on the membrane of cancer cells, inhibiting their metastatic potential in vitro. However, the reduced signaling entities responsible for the observed functional outputs remain elusive...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29329391/oxidative-burst-and-dectin-1-triggered-phagocytosis-affected-by-norepinephrine-and-endocannabinoids-implications-for-fungal-clearance-under-stress
#3
Judith-Irina Buchheim, Spencer Hoskyns, Dominique Moser, Bing Han, Elisabeth Deindl, Marion Hörl, Katharina Biere, Matthias Feuerecker, Gustav Schelling, Alexander Chouker
A prolonged stress burden is known to hamper the efficiency of both the innate and adaptive immune systems and to attenuate the stress responses by the catecholaminergic and endocannabinoid (EC) systems. Key mechanisms of innate immunity are the eradication of pathogens through phagocytosis and the respiratory burst. We tested the concentration-dependent, spontaneous and stimulated (via TNFα and fMLP) release of reactive oxygen species (ROS) by human PMNs in vitro in response to norepinephrine (NE) and AM1241, a pharmacological ligand for the endocannabinoid receptor CB2...
January 10, 2018: International Immunology
https://www.readbyqxmd.com/read/29325278/-effect-of-cannabinoid-receptor-2-agonist-am1241-on-platelet-derived-growth-factor-expression-in-the-liver-tissue-of-mice-with-hepatic-fibrosis
#4
P He, Y F Wu, H Y Yang, M L Cheng, Y D Liang, Y P Wang
Objective: To investigate the effect of cannabinoid receptor-2 (CB2) agonist AM1241 on the mRNA and protein expression of platelet-derived growth factor (PDGF) and collagen-III (Col-III) in the liver tissue of mice with experimental liver fibrosis induced by carbon tetrachloride (CCl(4)). Methods: Totally 38 8-week-old male C57BL/6J mice were randomly divided into control group, model group, 3 mg/kg CB2 receptor agonist (AM1241) group, and 9 mg/kg AM1241 group. All mice, except for the control group, were treated with 30% CCl(4) (three times a week, 5 ml/kg body weight, 16 weeks) to establish a liver fibrosis model...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29314831/a-fluorescent-probe-to-unravel-functional-features-of-cannabinoid-receptor-cb1-in-human-blood-and-tonsil-immune-system-cells
#5
Mar Martín-Fontecha, Alba Angelina, Beate Rückert, Ainoa Rueda-Zubiaurre, Leticia Martin-Cruz, Willem van de Veen, Mübeccel Akdis, Silvia Ortega-Gutierrez, María L López-Rodrí Guez, Cezmi Akdis, Oscar Palomares
The human endogenous cannabinoid system (ECS) regulates key physiological processes and alterations in its signalling pathways and endocannabinoid levels are associated to diseases such as neurological and neuropsychiatric conditions, cancer, pain and inflammation, obesity, metabolic and different immune related disorders. Immune system cells express the G-protein coupled cannabinoid receptor 1 (CB1) but its functional role has not been fully understood, likely due to the lack of appropriate tools. The availability of novel tools to investigate the role of CB1 in immune regulation might contribute to identify CB1 as a potential novel therapeutic target or biomarker for many diseases...
January 9, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29306933/mechanisms-and-treatment-of-painful-neuromas
#6
Changfeng Lu, Xun Sun, Chong Wang, Yu Wang, Jiang Peng
A painful neuroma is a common complication of a peripheral nerve injury or amputation, and it can cause tremendous pain that is resistant to most analgesics. Furthermore, painful neuromas have a high postoperative recurrence rate. Painful neuromas are often accompanied by functional disorders, drastically reducing the patient's quality of life. Several pathophysiological mechanisms have been proposed to explain this type of neuropathic pain, including peripheral and central sensitisation and the involvement of nerve growth factor, α-smooth muscle actin, the cannabinoid CB2 receptor and structural changes in neuroma fibres...
January 8, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29305938/ca2-dependent-potassium-channels-and-cannabinoid-signaling-in-the-endothelium-of-apolipoprotein-e-knockout-mice-before-plaque-formation
#7
Alexander I Bondarenko, Olga Panasiuk, Iryna Okhai, Fabrizio Montecucco, Karim J Brandt, François Mach
Endothelial Ca2+-dependent K+ channels (KCa) regulate endothelial function. We also know that stimulation of type 2 cannabinoid (CB2) receptors ameliorates atherosclerosis. However, whether atherosclerosis is accompanied by altered endothelial KCa- and CB2 receptor-dependent signaling is unknown. By utilizing an in situ patch-clamp approach, we directly evaluated the KCa channel function and the CB2 receptor-dependent electrical responses in the endothelium of aortic strips from young ApoE-/- and C57Bl/6 mice...
January 3, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29288767/surprising-outcomes-in-cannabinoid-cb1-cb2-receptor-double-knockout-mice-in-two-models-of-ischemia
#8
Sara Jane Ward, Francesca Castelli, Zachary W Reichenbach, Ronald F Tuma
AIMS: We tested the hypothesis that CB1/CB2 receptor double knockout would produce significant increases in infarct size and volume and significant worsening in clinical score, using two mouse models, one of permanent ischemia and one of ischemia/reperfusion. MAIN METHODS: Focal cerebral infarcts were created using either photo induced permanent injury or transient middle cerebral artery occlusion. Infarct volume and motor function were evaluated in cannabinoid receptor 1/cannabinoid receptor 2 double knockout mice...
December 27, 2017: Life Sciences
https://www.readbyqxmd.com/read/29285308/decisive-role-of-p42-44-mitogen-activated-protein-kinase-in-%C3%AE-9-tetrahydrocannabinol-induced-migration-of-human-mesenchymal-stem-cells
#9
Ellen Lüder, Robert Ramer, Kirsten Peters, Burkhard Hinz
In past years, medical interest in Δ9-tetrahydrocannabinol (THC), the major psychoactive ingredient of the Cannabis plant, has been renewed due to the elucidation of the endocannabinoid system and diverse other receptor targets involved in biological cannabinoid effects. The present study therefore investigates the impact of THC on the migration of mesenchymal stem cells (MSCs) which are known to be involved in various regenerative processes such as bone healing. Using Boyden chamber assays, THC was found to increase the migration of adipose-derived MSCs...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284441/expression-of-cannabinoid-1-and-2-receptors-and-the-effects-of-cannabinoid-1-and-2-receptor-agonists-on-detrusor-overactivity-associated-with-bladder-outlet-obstruction-in-rats
#10
Sung Dae Kim, Kang Jun Cho, Joon Chul Kim
BACKGROUND: This study investigated changes in the expression of cannabinoid (CB) receptors and the effects of CB1 and CB2 agonists on detrusor overactivity (DO) associated with bladder outlet obstruction (BOO) in rats. METHODS: Male Sprague Dawley rats were randomly assigned to four groups (n = 10) in each group. The control group comprised sham-operated rats. A animals in the BOO, CB1 agonist and CB2 agonist groups all underwent BOO surgery. Three weeks postoperatively, cystometrography (CMG) was performed on all rats...
December 29, 2017: BMC Urology
https://www.readbyqxmd.com/read/29274880/cb1-cannabinoid-receptor-agonist-mouse-vd-hemopressin-%C3%AE-produced-supraspinal-analgesic-activity-in-the-preclinical-models-of-pain
#11
Ting Zheng, Run Zhang, Ting Zhang, Meng-Na Zhang, Biao Xu, Jing-Jing Song, Ning Li, Hong-Hai Tang, Pei Wang, Rui Wang, Quan Fang
Mouse VD-hemopressin(α) (VD-Hpα) is an undecapeptide that selectively activates CB1 cannabinoid receptor in in vitro functional tests, and exerts CB1-mediated central antinociception in the mouse tail-flick assay. The aim of the present study was to further investigate the analgesic properties of supraspinal mouse VD-Hpα in a range of preclinical pain models. Our results indicated that the classical cannabinoid agonist WIN 55,212-2 produced supraspinal analgesia in preclinical pain models, which was selectively antagonized by the CB1 antagonist/inverse agonist AM251, but not by the CB2 antagonist AM630...
December 21, 2017: Brain Research
https://www.readbyqxmd.com/read/29259753/discovery-of-apd371-identification-of-a-highly-potent-and-selective-cb2-agonist-for-the-treatment-of-chronic-pain
#12
Sangdon Han, Lars Thoresen, Jae-Kyu Jung, Xiuwen Zhu, Jayant Thatte, Michelle Solomon, Ibragim Gaidarov, David J Unett, Woo Hyun Yoon, Jeremy Barden, Abu Sadeque, Amin Usmani, Chuan Chen, Graeme Semple, Andrew J Grottick, Hussein Al-Shamma, Ronald Christopher, Robert M Jones
The discovery of a novel, selective and fully efficacious CB2 agonist with satisfactory pharmacokinetic and pharmaceutical properties is described. Compound 6 was efficacious in a rat model of osteoarthritis pain following oral administration and, in contrast to morphine, maintained its analgesic effect throughout a 5-day subchronic treatment paradigm. These data were consistent with our hypothesis that full agonist efficacy is required for efficient internalization and recycling of the CB2 receptor to avoid tachyphylaxis...
December 14, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29247851/the-involvement-of-the-endocannabinoid-system-in-the-peripheral-antinociceptive-action-of-ketamine
#13
Renata C M Ferreira, Marina G M Castor, Fabiana Piscitelli, Vincenzo Di Marzo, Igor D G Duarte, Thiago R L Romero
Ketamine has been widely used as an analgesic and produces dissociative anesthetic effects. The antinociceptive effects of ketamine have been studied, but the involvement of endocannabinoids in these effects has not yet been investigated. In this study, we evaluated the involvement of the endocannabinoid system in the peripheral antinociceptive effects induced by ketamine. All drugs were administered via the intraplantar route. To induce hyperalgesia, rat paws were injected with prostaglandin E2 (PGE2, 2 µg/paw)...
December 13, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29238581/a-spicy-status-synthetic-cannabinoid-spice-use-and-new-onset-refractory-status-epilepticus-a-case-report-and-review-of-the-literature
#14
Marc-Alain Babi, Christopher P Robinson, Carolina B Maciel
Synthetic cannabinoids refer to a wide variety of chemicals engineered to bind cannabinoid receptors (CB1 and CB2) and mimic the effects of delta-9-tetrahydrocanabinol. The potential for severe toxicity and limited in vivo data make synthetic cannabinoid intake an important public health and safety concern. Neurologic toxidromes associated with their use include mental status changes, panic attacks, memory distortions, acute psychosis (e.g. paranoia, delusional thoughts), disorganized behavior, and suicidal and homicidal thoughts...
2017: SAGE Open Medical Case Reports
https://www.readbyqxmd.com/read/29234141/cannabinoid-type-2-receptors-in-dopamine-neurons-inhibits-psychomotor-behaviors-alters-anxiety-depression-and-alcohol-preference
#15
Qing-Rong Liu, Ana Canseco-Alba, Hai-Ying Zhang, Patricia Tagliaferro, Monika Chung, Eugene Dennis, Branden Sanabria, Norman Schanz, Joao Carlos Escosteguy-Neto, Hiroki Ishiguro, Zhicheng Lin, Susan Sgro, Claire M Leonard, Jair Guilherme Santos-Junior, Eliot L Gardner, Josephine M Egan, Jeung Woon Lee, Zheng-Xiong Xi, Emmanuel S Onaivi
Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29232588/bioactive-products-from-singlet-oxygen-photooxygenation-of-cannabinoids
#16
Ahmed Galal Osman, Khaled M Elokely, Vivek K Yadav, Paulo Carvalho, Mohamed Radwan, Desmond Slade, Waseem Gul, Shabana Khan, Olivia R Dale, Afeef S Husni, Michael L Klein, Stephen J Cutler, Samir A Ross, Mahmoud A ElSohly
Photooxygenation of Δ8 tetrahydrocannabinol (Δ8-THC), Δ9 tetrahydrocannabinol (Δ9-THC), Δ9 tetrahydrocannabinolic acid (Δ9-THCA) and some derivatives (acetate, tosylate and methyl ether) yielded 24 oxygenated derivatives, 18 of which were new and 6 were previously reported, including allyl alcohols, ethers, quinones, hydroperoxides, and epoxides. Testing these compounds for their modulatory effect on cannabinoid receptors CB1 and CB2 led to the identification of 7 and 21 as CB1 partial agonists with Ki values of 0...
November 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29229226/novel-sulfenamides-and-sulfonamides-based-on-pyridazinone-and-pyridazine-scaffolds-as-cb1-receptor-ligand-antagonists
#17
Gabriele Murineddu, Francesco Deligia, Giulio Ragusa, Laura García-Toscano, María Gómez-Cañas, Battistina Asproni, Valentina Satta, Elena Cichero, Ruth Pazos, Paola Fossa, Giovanni Loriga, Javier Fernández-Ruiz, Gerard A Pinna
A series of sulfenamide and sulfonamide derivatives was synthesized and evaluated for the affinity at CB1 and CB2 receptors. The N-bornyl-S-(5,6-di-p-tolylpyridazin-3-yl)-sulfenamide, compound 11, displayed good affinity and high selectivity for CB1 receptors (Ki values of 44.6 nM for CB1 receptors and >40 μM for CB2 receptors, respectively). The N-isopinocampheyl-sulfenamide 12 and its sulfonamide analogue 22 showed similar selectivity for CB1 receptors with Ki values of 75.5 and 73.2 nM, respectively...
December 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29225001/dorsal-hippocampal-cannabinergic-and-gabaergic-systems-modulate-memory-consolidation-in-passive-avoidance-task
#18
Mohammad Nasehi, Parisa Gerami, Fatemeh Khakpai, Mohammad-Reza Zarrindast
In the present research, we examined the possible interaction between the hippocampal CB2 and GABAA receptors on modulation of memory consolidation. In this research, step-down passive avoidance task was used to evaluate memory consolidation in adult male NMRI mice. The results showed that post-training intra-CA1 administration of muscimol (0.05 and 0.1μg/mouse) impaired memory consolidation as evidenced by a decrease in step-down latency on the test day, which was suggestive of drug-produced amnesia. However co-administration of different doses of muscimol (0...
December 7, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29218862/the-presence-and-distribution-of-cannabinoid-type-1-and-2-receptors-in-the-mandibular-gland-the-influence-of-different-physical-forms-of-diets-on-their-expression-in-piglets
#19
C Pirino, M G Cappai, M Maranesi, D Tomassoni, A Giontella, W Pinna, C Boiti, J Kamphues, C Dall'Aglio
We explored the expression and cell type distribution of cannabinoid receptors type 1 (CB1) and cannabinoid receptors type 2 (CB2) in the mandibular glands of pigs in relation to different physical forms of the diet. Thirty-two crossbred growing pigs (ages 5-6 weeks) were randomly allotted to four experimental groups (eight pigs/group) and fed four different physical types of the same diet for 4 weeks: finely ground pellet (FP), coarsely ground meal (CM), coarsely ground pellet (CP) and coarsely ground extruded (CE) with dMEAN of 0...
December 7, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/29192123/the-slowly-signaling-g-protein-biased-cb2-cannabinoid-receptor-agonist-ly2828360-suppresses-neuropathic-pain-with-sustained-efficacy-and-attenuates-morphine-tolerance-and-dependence
#20
Xiaoyan Lin, Amey S Dhopeshwarkar, Megan Huibregtse, Ken Mackie, Andrea G Hohmann
The CB2 cannabinoid agonist LY2828360 lacked both toxicity and efficacy in a clinical trial for osteoarthritis. Whether LY2828360 suppresses neuropathic pain has not been reported and its signaling profile is unknown. In vitro, LY2828360 was a slowly acting but efficacious G protein-biased CB2 agonist, inhibiting cAMP accumulation and activating ERK1/2 signaling while failing to recruit arrestin, activate inositol phosphate signaling or internalize CB2 receptors. In wildtype (WT) mice, LY2828360 (3 mg/kg/day i...
November 30, 2017: Molecular Pharmacology
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