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https://www.readbyqxmd.com/read/29792186/involvement-of-the-cb-2-cannabinoid-receptor-in-cell-growth-inhibition-and-g0-g1-cell-cycle-arrest-via-the-cannabinoid-agonist-win-55-212-2-in-renal-cell-carcinoma
#1
Mohammed I Khan, Anna A Sobocińska, Klaudia K Brodaczewska, Katarzyna Zielniok, Malgorzata Gajewska, Claudine Kieda, Anna M Czarnecka, Cezary Szczylik
BACKGROUND: The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB1 and CB2 ), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB 1 and CB 2 receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB1 and CB2 receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists [such as JWH-133 and WIN 55,212-2 (WIN-55)] in RCC cell lines...
May 23, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29791076/effects-of-endurance-training-on-hippocampus-dj-1-cb-2-and-blood-glucose-concentration-in-diabetic-rats
#2
Mohammad Kurd, Vahid Valipour Dehnou, Seyed Asadollah Tavakoli, Daniel E Gahreman
AIMS: To investigate the effect of endurance training on Hippocampus DJ-1 and CB2 protein and blood glucose concentration in diabetic rats. MATERIALS AND METHODS: Thirty-two rats were randomly divided into Diabetic (D), Diabetic and Exercise (DE), Exercise (E), and Control (C) groups. The endurance training was performed five times per week for six weeks. The hippocampus DJ-1 and CB2 were measured using an ELISA method. RESULTS: The level of DJ-1 in D group was significantly higher than other groups (p ≤ 0...
May 23, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29786105/cannabinoid-win-55-212-2-mesylate-inhibits-tumor-necrosis-factor-%C3%AE-induced-expression-of-nitric-oxide-synthase-in-dorsal-root-ganglion-neurons
#3
Rong Tan, Lijun Cao
Tumor necrosis factor-α (TNF-α) is an established pain modulator in the peripheral nervous system. Elevated levels of TNF-α in dorsal root ganglion (DRG) neurons reportedly is critical for neuropathic pain processing. It has been shown that the production of nitric oxide, a key player in the development and maintenance of nociception, depends on the expression of nitric oxide synthases (NOSs) and their activities. Accumulating evidence also supports an important role of cannabinoids in modulating neuropathic pain...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29773016/is-cannabidiol-a-promising-substance-for-new-drug-development-a-review-of-its-potential-therapeutic-applications
#4
Nida Noreen, Faqir Muhammad, Bushra Akhtar, Farooq Azam, Muhammad Irfan Anwar
The pharmacological importance of cannabidiol (CBD) has been in study for several years. CBD is the major nonpsychoactive constituent of plant Cannabis sativa and its administration is associated with reduced side effects. Currently, CBD is undergoing a lot of research which suggests that it has no addictive effects, good safety profile and has exhibited powerful therapeutic potential in several vital areas. It has wide spectrum of action because it acts through endocannabinoid receptors; CB1 and CB2 and it also acts on other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2...
2018: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/29770478/the-endocannabinoid-alcohol-crosstalk-recent-advances-on-a-bi-faceted-target
#5
REVIEW
Gianluca Lavanco, Valentina Castelli, Anna Brancato, Giuseppe Tringali, Fulvio Plescia, Carla Cannizzaro
Increasing evidence focuses on the endocannabinoid system as a relevant player in the induction of aberrant synaptic plasticity and related addictive phenotype following chronic excessive alcohol drinking. Besides, the endocannabinoid system is implicated in the pathogenesis of alcoholic liver disease. Interestingly, whereas the involvement of CB1 cannabinoid receptors in alcohol rewarding properties is established, the central and peripheral action of CB2 cannabinoid signalling is still to be elucidated. This review aims at giving the input to deepen knowledge on the role of the endocannabinoid system, highlighting the advancing evidence that suggests that CB1 and CB2 receptors may play opposite roles in the regulation of both the reinforcing properties of alcohol in the brain and the mechanisms responsible for cell injury and inflammation in the hepatic tissue...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29765535/effects-of-cb2-and-trpv1-receptors-stimulation-in-pediatric-acute-t-lymphoblastic-leukemia
#6
Francesca Punzo, Iolanda Manzo, Chiara Tortora, Elvira Pota, Velia D' Angelo, Giulia Bellini, Alessandra Di Paola, Federica Verace, Fiorina Casale, Francesca Rossi
T-Acute Lymphoblastic Leukemia (T-ALL) is less frequent than B-ALL, but it has poorer outcome. For this reason new therapeutic approaches are needed to treat this malignancy. The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G-Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells, therefore we chose to selectively stimulate CB2 and TRPV1...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29759062/inhibition-of-2-ag-hydrolysis-differentially-regulates-blood-brain-barrier-permeability-after-injury
#7
Justin R Piro, Georgette L Suidan, Jie Quan, YeQing Pi, Sharon M O'Neill, Marissa Ilardi, Nikolay Pozdnyakov, Thomas A Lanz, Hualin Xi, Robert D Bell, Tarek A Samad
BACKGROUND: Acute neurological insults caused by infection, systemic inflammation, ischemia, or traumatic injury are often associated with breakdown of the blood-brain barrier (BBB) followed by infiltration of peripheral immune cells, cytotoxic proteins, and water. BBB breakdown and extravasation of these peripheral components into the brain parenchyma result in inflammation, oxidative stress, edema, excitotoxicity, and neurodegeneration. These downstream consequences of BBB dysfunction can drive pathophysiological processes and play a substantial role in the morbidity and mortality of acute and chronic neurological insults, and contribute to long-term sequelae...
May 14, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29754307/effects-of-cocaine-self-administration-and-its-extinction-on-the-rat-brain-cannabinoid-cb1-and-cb2-receptors
#8
Beata Bystrowska, Małgorzata Frankowska, Irena Smaga, Lucyna Pomierny-Chamioło, Małgorzata Filip
The aim of this study was to evaluate changes in the expression of cannabinoid type 1 (CB1) and 2 (CB2) receptor proteins in several brain regions in rats undergoing cocaine self-administration and extinction training. We used a triad-yoked procedure to distinguish between the motivational and pharmacological effects of cocaine. Using immunohistochemistry, we observed a significant decrease in CB1 receptor expression in the prefrontal cortex, dorsal striatum, and the basolateral and basomedial amygdala following cocaine (0...
May 12, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29740328/emerging-role-of-endo-cannabinoids-in-migraine
#9
REVIEW
Pinja Leimuranta, Leonard Khiroug, Rashid Giniatullin
In this mini-review, we summarize recent discoveries and present new hypotheses on the role of cannabinoids in controlling trigeminal nociceptive system underlying migraine pain. Individual sections of this review cover key aspects of this topic, such as: (i) the current knowledge on the endocannabinoid system (ECS) with emphasis on expression of its components in migraine related structures; (ii) distinguishing peripheral from central site of action of cannabinoids, (iii) proposed mechanisms of migraine pain and control of nociceptive traffic by cannabinoids at the level of meninges and in brainstem, (iv) therapeutic targeting in migraine of monoacylglycerol lipase and fatty acid amide hydrolase, enzymes which control the level of endocannabinoids; (v) dual (possibly opposing) actions of cannabinoids via anti-nociceptive CB1 and CB2 and pro-nociceptive TRPV1 receptors...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29736745/activation-of-the-cannabinoid-type-2-receptor-by-a-novel-indazole-derivative-normalizes-the-survival-pattern-of-lymphoblasts-from-patients-with-late-onset-alzheimer-s-disease
#10
Patricia Del Cerro, Carolina Alquézar, Fernando Bartolomé, Pedro González-Naranjo, Concepción Pérez, Eva Carro, Juan A Páez, Nuria E Campillo, Ángeles Martín-Requero
BACKGROUND: Alzheimer's disease is a multifactorial disorder for which there is no disease-modifying treatment yet. CB2 receptors have emerged as a promising therapeutic target for Alzheimer's disease because they are expressed in neuronal and glial cells and their activation has no psychoactive effects. OBJECTIVE: The aim of this study was to investigate whether activation of the CB2 receptor would restore the aberrant enhanced proliferative activity characteristic of immortalized lymphocytes from patients with late-onset Alzheimer's disease...
May 7, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29729431/effects-of-cannabinoid-type-2-receptor-agonist-am1241-on-morphine-induced-antinociception-acute-and-chronic-tolerance-and-dependence-in-mice
#11
Mingyue Zhang, Linlin Dong, Huichao Zou, Junnan Li, Quanyi Li, Guonian Wang, Hulun Li
Morphine is a potent opioid analgesic used to alleviate moderate or severe pain but the development of drug tolerance and dependence limits its use in pain management. Previous studies showed that cannabinoid type 2 (CB2 ) receptor ligands may modulate opioid effects. However, there is no report of the effect of CB2 receptor agonist on acute morphine tolerance and physical dependence. We therefore investigated the effect of a CB2 receptor agonist (AM1241) on morphine-induced morphine tolerance and physical dependence in mice...
May 2, 2018: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29694791/genetic-variant-q63r-of-cannabinoid-receptor-2-cb2r-causes-differential-erk-phosphorylation-in-human-immune-cells
#12
Jingru Wang, Juehua Xu, Jie Liu, Huang Zhu, Yanyan Peng, Zhi-Ming Ding, Haiqing Hua
BACKGROUND: The cannabinoid receptor 2 (CB2R) is primarily expressed in immune tissues and implicated in immune regulation. In models of inflammatory diseases, modulation of CB2R alters function of immune cells and affects the progression of disease. We therefore believe that CB2R modulation could be a promising therapy for inflammatory diseases. In humans, the nonsynonymous mutation Q63R, the most common variant of the CB2 receptor, has been found to be associated with multiple diseases, including idiopathic arthritis, obesity, and celiac diseases...
April 25, 2018: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29669714/cannabidiol-inhibits-endocannabinoid-signaling-in-autaptic-hippocampal-neurons
#13
Alex Straiker, Michaela Dvorakova, Anaelle Zimmowitch, Ken P Mackie
Δ9-THC and cannabidiol (CBD) are two main cannabinoid constituents of marijuana and hashish. The pharmacology of Δ9-THC has been extensively studied, while our understanding of the pharmacology of CBD has remained limited, despite excitement in CBD's potential role in treating certain pediatric epilepsies and its reputation for attenuating some Δ9-THC-induced effects. It was established early on that CBD binds poorly to the orthosteric site of CB1 or CB2 cannabinoid receptors and its actions were commonly attributed to other non-cannabinoid receptor mechanisms...
April 18, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29662438/cannabinoid-receptor-type-1-expression-in-the-developing-avian-retina-morphological-and-functional-correlation-with-the-dopaminergic-system
#14
Luzia da Silva Sampaio, Regina C C Kubrusly, Yolanda P Colli, Priscila P Trindade, Victor T Ribeiro-Resende, Marcelo Einicker-Lamas, Roberto Paes-de-Carvalho, Patricia F Gardino, Fernando G de Mello, Ricardo A De Melo Reis
The avian retina has been used as a model to study signaling by different neuro- and gliotransmitters. It is unclear how dopaminergic and cannabinoid systems are related in the retina. Here we studied the expression of type 1 and 2 cannabinoid receptors (CB1 and CB2 ), as well as monoacylglycerol lipase (MAGL), the enzyme that degrades 2-arachidonoylglycerol (2-AG), during retina development. Our data show that CB1 receptor is highly expressed from embryonic day 5 (E5) until post hatched day 7 (PE7), decreasing its levels throughout development...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29624642/cannabidiol-regulates-behavioural-alterations-and-gene-expression-changes-induced-by-spontaneous-cannabinoid-withdrawal
#15
Francisco Navarrete, Auxiliadora Aracil-Fernández, Jorge Manzanares
BACKGROUND AND PURPOSE: Cannabidiol (CBD) represents a promising therapeutic tool for treating cannabis use disorder (CUD). This study aimed to evaluate the effects of CBD on the behavioural and gene expression alterations induced by spontaneous cannabinoid withdrawal. EXPERIMENTAL APPROACH: Spontaneous cannabinoid withdrawal was evaluated 12 h after cessation of CP-55,940 treatment (0.5 mg·kg-1 /12 h; intraperitoneally (i.p.); 7 days) in C57BL/6J mice. The effects of CBD (5, 10 and 20 mg·kg-1 ; i...
April 6, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29618679/low-risk-of-pulmonary-vein-stenosis-after-contemporary-atrial-fibrillation-ablation-lessons-from-repeat-procedures-after-radiofrequency-current-cryoballoon-and-laser-balloon
#16
Takahiko Nagase, Stefano Bordignon, Laura Perrotta, Fabrizio Bologna, Felix K Weise, Athanasios Konstantinou, Ritsushi Kato, Boris Schmidt, Julian K R Chun
BACKGROUND: The incidence of pulmonary vein stenosis (PVS) after AF ablation following contemporary procedures remains unclear. We compared the incidence of PVS/narrowing (PVS/N) after PV isolation (PVI) for (1) 3-D mapping-guided wide-area encircling irrigated radiofrequency current (RFC) ablation; (2) first-third-generation big cryoballoon (CB1-3) ablation; and (3) laser balloon (LB) ablation.Methods and Results:All patients undergoing a second procedure between January 2012 and November 2016 were subgrouped according to index ablation (PVI): RFC; CB; or LB...
April 5, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29601300/cannabinoids-in-health-and-disease-pharmacological-potential-in-metabolic-syndrome-and-neuroinflammation
#17
REVIEW
Andrea Mastinu, Marika Premoli, Giulia Ferrari-Toninelli, Simone Tambaro, Giuseppina Maccarinelli, Maurizio Memo, Sara Anna Bonini
The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena. In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving. Moreover, cannabinoid agonists are able to reduce inflammatory response...
March 30, 2018: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/29574689/targeting-glial-cb-2-receptors-to-delay-the-progression-of-the-pathological-phenotype-in-tdp-43-a315t-transgenic-mice-a-model-of-amyotrophic-lateral-sclerosis
#18
Francisco Espejo-Porras, Laura García-Toscano, Carmen Rodríguez-Cueto, Irene Santos-García, Eva de Lago, Javier Fernández-Ruiz
BACKGROUND AND PURPOSE: CB2 receptors up-regulate in reactive microglia in the spinal cord of TDP-43(A315T) transgenic mice, an experimental model of ALS. To determine whether such up-regulation may be pharmacologically exploited, we investigated different treatments modulating the CB2 receptor function. EXPERIMENTAL APPROACH: We treated TDP-43(A315T) transgenic mice with the non-selective agonist WIN55,212-2, alone or combined with selective CB1 or CB2 antagonists, as well as with the selective CB2 agonist HU-308, and evaluated their effects on the pathological phenotype...
March 25, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29574067/structure-kinetic-relationship-studies-of-cannabinoid-cb-2-receptor-agonists-reveal-substituent-specific-lipophilic-effects-on-residence-time
#19
Marjolein Soethoudt, Mark W H Hoorens, Ward Doelman, Andrea Martella, Mario van der Stelt, Laura H Heitman
A decade ago, the drug-target residence time model has been (re-)introduced, which describes the importance of binding kinetics of ligands on their protein targets. Since then, it has been applied successfully for multiple protein targets, including GPCRs, for the development of lead compounds with slow dissociation kinetics (i.e. long target residence time) to increase in vivo efficacy or with short residence time to prevent on-target associated side effects. To date, this model has not been applied in the design and pharmacological evaluation of novel selective ligands for the cannabinoid CB2 receptor (CB2 R), a GPCR with therapeutic potential in the treatment of tissue injury and inflammatory diseases...
March 21, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29560022/paeoniflorin-exerts-neuroprotective-effects-by-modulating-the-m1-m2-subset-polarization-of-microglia-macrophages-in-the-hippocampal-ca1-region-of-vascular-dementia-rats-via-cannabinoid-receptor-2
#20
Xian-Qin Luo, Ao Li, Xue Yang, Xiao Xiao, Rong Hu, Tian-Wen Wang, Xiao-Yun Dou, Da-Jian Yang, Zhi Dong
Background: Cerebral hypoperfusion is a pivotal risk factor for vascular dementia (VD), for which effective therapy remains inadequate. Persistent inflammatory responses and excessive chemotaxis of microglia/macrophages in the brain may accelerate the progression of VD. Endocannabinoids are involved in neuronal protection against inflammation-induced neuronal injury. Cannabinoids acting at cannabinoid receptor 2 (CB2 R) can decrease inflammation. Based on the identification of paeoniflorin (PF) as a CB2 R agonist, we investigated the neuroprotective and microglia/macrophages M1 to M2 polarization promoting effects of PF in a permanent four-vessel occlusion rat model...
2018: Chinese Medicine
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