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https://www.readbyqxmd.com/read/29781960/a-peripherally-restricted-cannabinoid-1-receptor-agonist-as-a-novel-analgesic-in-cancer-induced-bone-pain
#1
Hong Zhang, Dominique M Lund, Haley A Ciccone, William D Staatz, Mohab M Ibrahim, Tally M Largent-Milnes, Herbert H Seltzman, Igor Spigelman, Todd W Vanderah
Many malignant cancers, including breast cancer, have a propensity to invade bones, leading to excruciating bone pain. Opioids are the primary analgesics used to alleviate this cancer-induced bone pain (CIBP) but are associated with numerous severe side effects, including enhanced bone degradation, which significantly impairs patients' quality of life. In contrast, agonists activating only peripheral CB1 receptors (CB1Rs) have been shown to effectively alleviate multiple chronic pain conditions with limited side effects, yet no studies have evaluated their role(s) in CIBP...
May 16, 2018: Pain
https://www.readbyqxmd.com/read/29779943/astroglial-cb-1-receptors-determine-synaptic-d-serine-availability-to-enable-recognition-memory
#2
Laurie M Robin, José F Oliveira da Cruz, Valentin C Langlais, Mario Martin-Fernandez, Mathilde Metna-Laurent, Arnau Busquets-Garcia, Luigi Bellocchio, Edgar Soria-Gomez, Thomas Papouin, Marjorie Varilh, Mark W Sherwood, Ilaria Belluomo, Georgina Balcells, Isabelle Matias, Barbara Bosier, Filippo Drago, Ann Van Eeckhaut, Ilse Smolders, Francois Georges, Alfonso Araque, Aude Panatier, Stéphane H R Oliet, Giovanni Marsicano
Bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. D-serine is a necessary co-agonist of synaptic N-methyl-D-aspartate receptors (NMDARs), but the physiological factors regulating its impact on memory processes are scantly known. We show that astroglial CB1 receptors are key determinants of object recognition memory by determining the availability of D-serine at hippocampal synapses. Mutant mice lacking CB1 receptors from astroglial cells (GFAP-CB1 -KO) displayed impaired object recognition memory and decreased in vivo and in vitro long-term potentiation (LTP) at CA3-CA1 hippocampal synapses...
May 15, 2018: Neuron
https://www.readbyqxmd.com/read/29778010/exposure-to-cannabinoid-agonist-win-55-212-2-during-early-adolescence-increases-alcohol-preference-and-anxiety-in-cd1-mice
#3
Jimena Laura Frontera, Victoria María Gonzalez Pini, Fernando Luis Messore, Alicia Brusco
The endocannabinoid (eCB) system is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the central nervous system is the CB1 receptor (CB1R), which is predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area, the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development, and reaches maximum levels during early adolescence...
May 16, 2018: Neuropharmacology
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/29751000/2-arachidonoylglycerol-a-signaling-lipid-with-manifold-actions-in-the-brain
#9
REVIEW
Marc P Baggelaar, Mauro Maccarrone, Mario van der Stelt
2-Arachidonoylglycerol (2-AG) is a signaling lipid in the central nervous system that is a key regulator of neurotransmitter release. 2-AG is an endocannabinoid that activates the cannabinoid CB1 receptor. It is involved in a wide array of (patho)physiological functions, such as emotion, cognition, energy balance, pain sensation and neuroinflammation. In this review, we describe the biosynthetic and metabolic pathways of 2-AG and how chemical and genetic perturbation of these pathways has led to insight in the biological role of this signaling lipid...
May 8, 2018: Progress in Lipid Research
https://www.readbyqxmd.com/read/29740328/emerging-role-of-endo-cannabinoids-in-migraine
#10
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/29731737/lh-21-a-peripheral-cannabinoid-receptor-1-antagonist-exerts-favorable-metabolic-modulation-including-antihypertensive-effect-in-kkay-mice-by-regulating-inflammatory-cytokines-and-adipokines-on-adipose-tissue
#11
Ziqi Dong, Hui Gong, Yadan Chen, Hong Wu, Jun Wu, Yinghong Deng, Xinmao Song
Patients with obesity are susceptible to hypertension and diabetes. Over-activation of cannabinoid receptor 1 (CB1 R) in adipose tissue is proposed in the pathophysiology of metabolic disorders, which led to the metabolic dysfunction of adipose tissue and deregulated production and secretion of adipokines. In the current study, we determined the impact of LH-21, a representative peripheral CB1 R antagonist, on the obesity-accompanied hypertension and explored the modulatory action of LH-21 on the adipose tissue in genetically obese and diabetic KKAy mice...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29730318/a-real-time-screening-assay-for-cannabinoid-cb1-receptor-mediated-signaling
#12
Haley K Andersen, Kenneth B Walsh
The cannabinoid CB1 receptor is expressed throughout the central nervous system where it functions to regulate neurotransmitter release and synaptic plasticity. While the CB1 receptor has been identified as a target for both natural and synthetic cannabinoids, the specific downstream signaling pathways activated by these various ligands have not been fully described. In this study, we developed a real-time membrane potential fluorescent assay for cannabinoids using pituitary AtT20 cells that endogenously express G protein-gated inward rectifier K+ (GIRK) channels and were stably transfected with the CB1 receptor using a recombinant lentivirus...
May 3, 2018: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/29699000/spermidine-prevents-high-glucose-induced-senescence-in-ht-22-cells-by-upregulation-of-cb1-receptor
#13
Wei-Wen Zhu, Fan Xiao, Yi-Yun Tang, Wei Zou, Xiang Li, Ping Zhang, Ai-Ping Wang, Xiao-Qing Tang
Hyperglycemia-induced neurotoxicity involves in the pathogenesis of diabetic encephalopathy and neuronal senescence is one of the worst effects of hyperglycemic neurotoxicity. Cannabinoid receptor type 1 (CB1) has neuroprotective function in a series of neuropathy. Spermidine (Spd) has anti-aging function in many tissues. However, the role of Spd in hyperglycemia-induced neuronal senescence remains unexplored. Therefore, we used high glucose (HG)-treated HT-22 cell as vitro model to investigate whether Spd protects neurons against hyperglycemia-induced senescence and the mediatory role of CB1 receptor...
April 26, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29694340/possible-role-of-hippocampal-gpr55-in-spatial-learning-and-memory-in-rats
#14
Bruno A Marichal-Cancino, Alfonso Fajardo-Valdez, Alejandra E Ruiz-Contreras, Mónica Méndez-Díaz, Oscar Prospéro-García
Endocannabinoids (eCBs) are involved in the hippocampal mechanisms of spatial learning and memory in rats. Although eCBs exert many of their actions on spatial learning and memory via CB1 receptors, the putative cannabinoid receptor GPR55 (expressed in the hippocampus, cortex, forebrain, cerebellum and striatum) seems to be also involved. To investigate the potential role of GPR55 in spatial learning and memory, Wistar rats received bilateral infusions of lysophosphatidylinositol (LPI, GPR55‑agonist) into the hippocampus 5‑minutes before training‑phase in the Barnes‑maze (BM)...
2018: Acta Neurobiologiae Experimentalis
https://www.readbyqxmd.com/read/29688015/a-peripherally-restricted-purine-antagonist-of-type-1-cannabinoid-cb1-receptor-blocks-alcoholic-steatosis-in-mice
#15
George Amato, Amruta Manke, Danni L Harris, Robert W Wiethe, Vineetha Vasukuttan, Rodney W Snyder, Timothy W Lefever, Ricardo Cortes, Yanan Zhang, Shaobin Wang, Scott P Runyon, Rangan Maitra
Type 1 cannabinoid receptor (CB1) antagonists have demonstrated promise for the treatment of obesity, liver disease, metabolic syndrome and dyslipidemias. However, inhibition of CB1 receptors in the central nervous system can produce adverse effects including depression, anxiety and suicidal ideation. Efforts are now underway to produce peripherally restricted CB1 antagonists to circumvent CNS-associated undesirable effects. In this study, a series of analogs were explored in which the 4-aminopiperidine group of 2 was replaced with aryl and heteroaryl substituted piperazine groups both with and without a spacer...
April 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29687594/stereospecific-nucleophilic-substitution-with-arylboronic-acids-as-nucleophiles-a-crucial-conh-effect
#16
Wenjun Tang, Duanshuai Tian, Chengxi Li, Guoxian Gu, Xumu Zhang, Henian Peng
Stereospecific nucleophilic substitution is achieved for the first time with arylboronic acids as pure nuclephiles. The transition metal-free coupling between chiral α-aryl-α-mesylated acetamides and arylboronic acids have provided the initial syntheses of a series of chiral α,α-diaryl acetamides in excellent ees and moderate to good yields. The CONH functionality proved to be crucial in bridging both reactants and promoting the reaction. Efficient syntheses of a cannabinoid CB1-receptor, antidepressant (S)-diclofensine, and a key chiral building block of implitapide are successfully accomplished by using this method...
April 24, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29681797/electroacupuncture-potentiates-cannabinoid-receptor-mediated-descending-inhibitory-control-in-a-mouse-model-of-knee-osteoarthritis
#17
Xiao-Cui Yuan, Bing Zhu, Xiang-Hong Jing, Li-Ze Xiong, Cai-Hua Wu, Fang Gao, Hong-Ping Li, Hong-Chun Xiang, He Zhu, Bin Zhou, Wei He, Chuan-You Lin, Hui-Lin Pan, Qiang Wang, Man Li
Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, which can lead to chronic pain. Although electroacupuncture (EA) is effective in relieving chronic pain in the clinic, the involved mechanisms remain unclear. Reduced diffuse noxius inhibitory controls (DNIC) function is associated with chronic pain and may be related to the action of endocannabinoids. In the present study, we determined whether EA may potentiate cannabinoid receptor-mediated descending inhibitory control and inhibit chronic pain in a mouse model of KOA...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29678290/orexin-a-and-endocannabinoid-signaling-regulate-glucose-responsive-arcuate-nucleus-neurons-and-feeding-behavior-in-obese-rats
#18
Dandan Yang, Luo Xu, Feifei Guo, Xiangrong Sun, Di Zhang, Mi Wang
Obesity is a global public health problem. Orexin and endocannabinoid signaling in the hypothalamus have been shown to regulate feeding and are promising molecular targets for obesity treatment. In this study, we attempted to analyze effects of orexin-A and endocannabinoid signaling modulation in the arcuate nucleus (Arc) on feeding and glucose-responsive (GR) neurons physiology in a diet-induced obesity (DIO) and diet-induced obesity resistant (DR) rat model. Administration of orexin-A or cannabinoid receptor type-1 (CB1 R) antagonist AM251 altered the firing of GR neurons in the Arc...
April 6, 2018: Neuropeptides
https://www.readbyqxmd.com/read/29678287/novel-mechanisms-of-g-protein-coupled-receptors-functions-at-1-angiotensin-receptor-acts-as-a-signaling-hub-and-focal-point-of-receptor-cross-talk
#19
REVIEW
András D Tóth, Gábor Turu, László Hunyady, András Balla
AT1 angiotensin receptor (AT1 R), a prototypical G protein-coupled receptor (GPCR), is the main receptor, which mediates the effects of the renin-angiotensin system (RAS). AT1 R plays a crucial role in the regulation of blood pressure and salt-water homeostasis, and in the development of pathological conditions, such as hypertension, heart failure, cardiovascular remodeling, renal fibrosis, inflammation, and metabolic disorders. Stimulation of AT1 R leads to pleiotropic signal transduction pathways generating arrays of complex cellular responses...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29676731/oxytocin-functions-as-a-spatiotemporal-filter-for-excitatory-synaptic-inputs-to-vta-dopamine-neurons
#20
Lei Xiao, Michael F Priest, Yevgenia Kozorovitskiy
The experience of rewarding or aversive stimuli is encoded by distinct afferents to dopamine (DA) neurons of the ventral tegmental area (VTA). Several neuromodulatory systems including oxytocin regulate DA neuron excitability and synaptic transmission that process socially meaningful stimuli. We and others have recently characterized oxytocinergic modulation of activity in mouse VTA DA neurons, but the mechanisms underlying oxytocinergic modulation of synaptic transmission in DA neurons remain poorly understood...
April 20, 2018: ELife
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