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Cannabinoid receptors

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https://www.readbyqxmd.com/read/28214870/the-inhibitory-effect-of-s-777469-a-cannabinoid-type-2-receptor-agonist-on-skin-inflammation-in-mice
#1
Takayo Haruna, Masahiko Soga, Yasuhide Morioka, Kinichi Imura, Yoko Furue, Mina Yamamoto, Jun Hayakawa, Masashi Deguchi, Akinori Arimura, Kiyoshi Yasui
We investigated the effects of S-777469 (1-[[6-Ethyl-1-[4-fluorobenzyl]-5-methyl-2-oxo-1, 2-dihydropyridine-3-carbonyl]amino]-cyclohexanecarboxylic acid), a novel cannabinoid type 2 receptor (CB2) agonist, on 1-fluoro-2,4-dinitrobenzene (DNFB)-induced ear inflammation and mite antigen-induced dermatitis in mice. The oral administration of S-777469 significantly suppressed DNFB-induced ear swelling in a dose-dependent manner. In addition, S-777469 significantly alleviated mite antigen-induced atopic dermatitis-like skin lesions in NC/Nga mice...
February 18, 2017: Pharmacology
https://www.readbyqxmd.com/read/28213089/monoglyceride-lipase-as-a-drug-target-at-the-crossroads-of-arachidonic-acid-metabolism-and-endocannabinoid-signaling
#2
REVIEW
Gernot F Grabner, Robert Zimmermann, Rudolf Schicho, Ulrike Taschler
Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoylglycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body...
February 14, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28210722/synthesis-radio-synthesis-and-in-vitro-evaluation-of-terminally-fluorinated-derivatives-of-hu-210-and-hu-211-as-novel-candidate-pet-tracers
#3
Chiara Zanato, Alessia Pelagalli, Katie F M Marwick, Monica Piras, Sergio Dall'Angelo, Andrea Spinaci, Roger G Pertwee, David J A Wyllie, Giles E Hardingham, Matteo Zanda
We report the synthesis of terminally fluorinated HU-210 and HU-211 analogues (HU-210F and HU-211F, respectively) and their biological evaluation as ligands of cannabinoid receptors (CB1 and CB2) and N-methyl d-aspartate receptor (NMDAR). [(18)F]-labelled HU-210F was radiosynthesised from the bromo-substituted precursor. In vitro assays showed that both HU-210F and HU-211F retain the potent pharmacological profile of HU-210 and HU-211, suggesting that [(18)F]-radiolabelled HU-210F and HU-211F could have potential as PET tracers for in vivo imaging...
February 17, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28210207/cannabinoid-receptor-2-signaling-in-neurodegenerative-disorders-from-pathogenesis-to-a-promising-therapeutic-target
#4
REVIEW
Tommaso Cassano, Silvio Calcagnini, Lorenzo Pace, Federico De Marco, Adele Romano, Silvana Gaetani
As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28209996/transient-cannabinoid-receptor-2-blockade-during-immunization-heightens-intensity-and-breadth-of-antigen-specific-antibody-responses-in-young-and-aged-mice
#5
Emmanuel Dotsey, Irina Ushach, Egest Pone, Rie Nakajima, Algis Jasinskas, Donovan A Argueta, Andrea Dillon, Nicholas DiPatrizio, Huw Davies, Albert Zlotnik, Peter D Crompton, Philip L Felgner
The hallmark of vaccines is their ability to prevent the spread of infectious pathogens and thereby serve as invaluable public health tool. Despite their medical relevance, there is a gap in our understanding of the physiological factors that mediate innate and adaptive immune response to vaccines. The endocannabinoid (eCB) system is a critical modulator of homeostasis in vertebrates. Our results indicate that macrophages and dendritic cells produce the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG) upon antigen activation...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209735/the-epac-phospholipase-c%C3%AE%C2%B5-pathway-regulates-endocannabinoid-signaling-and-cocaine-induced-disinhibition-of-vta-dopamine-neurons
#6
Jiaqing Tong, Xiaojie Liu, Casey Vickstrom, Yan Li, Laikang Yu, Youming Lu, Alan V Smrcka, Qing-Song Liu
Exchange protein directly activated by cAMP (Epac) is a direct effector for the ubiquitous second messenger cAMP. Epac activates the phospholipase Cε (PLCε) pathway. PLCβ has been linked to the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG). Here, we report that Epac facilitates endocannabinoid-mediated retrograde synaptic depression through activation of PLCε. Intracellular loading of a selective Epac agonist 8-CPT-2Me-cAMP into ventral tegmental area (VTA) dopamine neurons enabled previously ineffective stimuli to induce depolarization-induced suppression of inhibition (DSI) and long-term depression of IPSCs (I-LTD) in the VTA...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28209423/constitutive-increases-in-amygdalar-corticotropin-releasing-factor-and-fatty-acid-amide-hydrolase-drive-an-anxious-phenotype
#7
Luis A Natividad, Matthew W Buczynski, Melissa A Herman, Dean Kirson, Christopher S Oleata, Cristina Irimia, Ilham Polis, Roberto Ciccocioppo, Marisa Roberto, Loren H Parsons
BACKGROUND: Corticotropin-releasing factor (CRF) mediates anxiogenic responses by activating CRF type 1 (CRF1) receptors in limbic brain regions. Anxiety is further modulated by the endogenous cannabinoid (eCB) system that attenuates the synaptic effects of stress. In the amygdala, acute stress activates the enzymatic clearance of the eCB N-arachidonoylethanolamine via fatty acid amide hydrolase (FAAH), although it is unclear whether chronic dysregulation of CRF systems induces maladaptive changes in amygdalar eCB signaling...
January 13, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28203147/astrocyte-dependent-slow-inward-currents-sics-participate-in-neuromodulatory-mechanisms-in-the-pedunculopontine-nucleus-ppn
#8
Adrienn Kovács, Balázs Pál
Slow inward currents (SICs) are known as excitatory events of neurons caused by astrocytic glutamate release and consequential activation of neuronal extrasynaptic NMDA receptors. In the present article we investigate the role of these astrocyte-dependent excitatory events on a cholinergic nucleus of the reticular activating system (RAS), the pedunculopontine nucleus (PPN). It is well known about this and other elements of the RAS, that they do not only give rise to neuromodulatory innervation of several areas, but also targets neuromodulatory actions from other members of the RAS or factors providing the homeostatic drive for sleep...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28196832/gpr55-a-new-promising-target-for-metabolism
#9
Eva Tuduri, Monica Imbernon, Rene Bautista, Marta Tojo, Johan Fernø, Carlos Diéguez, Rubén Nogueiras
GPR55 is a G-protein coupled receptor (GPCR) that has been identified as a new cannabinoid receptor. Given the wide localization of GPR55 in brain and peripheral tissues, this receptor has emerged as a regulator of multiple biological actions. Lysophosphatidylinositol (LPI) is generally accepted as the endogenous ligand of GPR55. In this review, we will focus on the role of GPR55 in energy balance and glucose metabolism. We will summarize its actions on feeding, nutrient partitioning, gastrointestinal motility and insulin secretion in preclinical models and the scarce data available in humans...
February 14, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28194850/cannabidiol-reduces-ethanol-consumption-motivation-and-relapse-in-mice
#10
Adrián Viudez-Martínez, María S García-Gutiérrez, Carmen María Navarrón, María Isabel Morales-Calero, Francisco Navarrete, Ana Isabel Torres-Suárez, Jorge Manzanares
This study evaluated the effects of cannabidiol (CBD) on ethanol reinforcement, motivation and relapse in C57BL/6 J mice. The effects of CBD (60 mg/kg, i.p.) on blood ethanol concentration, hypothermia and handling-induced convulsions associated to acute ethanol administration were evaluated. The two-bottle choice paradigm was performed to assess the effects of CBD (30, 60 and 120 mg/kg/day, i.p.) on ethanol intake and preference. In addition, an oral ethanol self-administration experiment was carried out to evaluate the effects of CBD [a single s...
February 13, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28194132/molecular-imaging-markers-to-track-huntington-s-disease-pathology
#11
REVIEW
Heather Wilson, Rosa De Micco, Flavia Niccolini, Marios Politis
Huntington's disease (HD) is a progressive, monogenic dominant neurodegenerative disorder caused by repeat expansion mutation in the huntingtin gene. The accumulation of mutant huntingtin protein, forming intranuclear inclusions, subsequently leads to degeneration of medium spiny neurons in the striatum and cortical areas. Genetic testing can identify HD gene carriers before individuals develop overt cognitive, psychiatric, and chorea symptoms. Thus, HD gene carriers can be studied in premanifest stages to understand and track the evolution of HD pathology...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28192788/metabolic-gatekeeper-function-of-b-lymphoid-transcription-factors
#12
Lai N Chan, Zhengshan Chen, Daniel Braas, Jae-Woong Lee, Gang Xiao, Huimin Geng, Kadriye Nehir Cosgun, Christian Hurtz, Seyedmehdi Shojaee, Valeria Cazzaniga, Hilde Schjerven, Thomas Ernst, Andreas Hochhaus, Steven M Kornblau, Marina Konopleva, Miles A Pufall, Giovanni Cazzaniga, Grace J Liu, Thomas A Milne, H Phillip Koeffler, Theodora S Ross, Isidro Sánchez-García, Arndt Borkhardt, Keith R Yamamoto, Ross A Dickins, Thomas G Graeber, Markus Müschen
B-lymphoid transcription factors, such as PAX5 and IKZF1, are critical for early B-cell development, yet lesions of the genes encoding these transcription factors occur in over 80% of cases of pre-B-cell acute lymphoblastic leukaemia (ALL). The importance of these lesions in ALL has, until now, remained unclear. Here, by combining studies using chromatin immunoprecipitation with sequencing and RNA sequencing, we identify a novel B-lymphoid program for transcriptional repression of glucose and energy supply...
February 13, 2017: Nature
https://www.readbyqxmd.com/read/28192193/differential-expression-of-endocannabinoid-system-related-genes-in-the-dorsal-hippocampus-following-expression-and-reinstatement-of-morphine-conditioned-place-preference-in-mice
#13
Wei Li, Cong-Li Zhang, Zheng-Guo Qiu
The endocannabinoid signaling plays a critical role in mediating rewarding effects to morphine. The relative stability for the expression and reinstatement of morphine conditioned place preference (CPP) suggests the involvement of differential neuroadaptations in learned associations between environmental cues and morphine. Changes in gene expression in hippocampus through the endogenous cannabinoid system (eCB) may accompany and mediate the development of such neuroadaptations to repeated morphine stimulation...
February 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28192082/endocannabinoid-dependent-protection-against-kainic-acid-induced-long-term-alteration-of-brain-oscillations-in-guinea-pigs
#14
Liubov Shubina, Rubin Aliev, Valentina Kitchigina
Changes in rhythmic activity can serve as early biomarkers of pathological alterations, but it remains unclear how different types of rhythmic activity are altered during neurodegenerative processes. Glutamatergic neurotoxicity, evoked by kainic acid (KA), causes hyperexcitation and acute seizures that result in delayed brain damage. We employed wide frequency range (0.1-300 Hz) local field potential recordings in guinea pigs to study the oscillatory activity of the hippocampus, entorhinal cortex, medial septum, and amygdala in healthy animals for three months after KA introduction...
February 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28191815/bladder-cancer-cell-growth-and-motility-implicate-cannabinoid-2-receptor-mediated-modifications-of-sphingolipids-metabolism
#15
Arianna Bettiga, Massimo Aureli, Giorgia Colciago, Valentina Murdica, Marco Moschini, Roberta Lucianò, Daniel Canals, Yusuf Hannun, Petter Hedlund, Giovanni Lavorgna, Renzo Colombo, Rosaria Bassi, Maura Samarani, Francesco Montorsi, Andrea Salonia, Fabio Benigni
The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC). CB expression on human normal and BC specimens was tested by immunohistochemistry. Human BC cells RT4 and RT112 were challenged with CB agonists and assessed for proliferation, apoptosis, and motility. Cellular sphingolipids (SL) constitution and metabolism were evaluated after metabolic labelling. CB1-2 were detected in BC specimens, but only CB2 was more expressed in the tumour...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191518/corticosteroids-the-oldest-agent-in-the-prevention-of-chemotherapy-induced-nausea-and-vomiting-what-about-the-guidelines
#16
Florence Van Ryckeghem
Chemotherapy-induced nausea and vomiting (CINV) remains one of the most disturbing side effects of cancer treatment. Research in antiemetic therapy has progressed gradually since the early eighties, and the development of antiemetic agents continues. This review focuses on the current management of CINV based on the most recent guidelines, and adherence to the latter is examined more carefully. Setrons (5HT3 receptor antagonists), corticosteroids, and NK-1 receptor antagonists are the cornerstones of antiemetic therapy...
April 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28190698/therapeutic-effects-of-cannabinoids-in-animal-models-of-seizures-epilepsy-epileptogenesis-and-epilepsy-related-neuroprotection
#17
REVIEW
Evan C Rosenberg, Pabitra H Patra, Benjamin J Whalley
The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection...
February 9, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28188777/enhanced-ability-of-trpv1-channels-in-regulating-glutamatergic-transmission-after-repeated-morphine-exposure-in-the-nucleus-accumbens-of-rat
#18
Haitao Zhang, Dong Jia, Yuan Wang, Liang Qu, Xuelian Wang, Jian Song, Lijun Heng, Guodong Gao
Glutamatergic projections to nucleus accumbens (NAc) drive drug-seeking behaviors during opioids withdrawal. Modulating glutamatergic neurotransmission provides a novel pharmacotherapeutic avenue for treatment of opioids dependence. Great deals of researches have verified that transient receptor potential vanilloid 1 (TRPV1) channels alters synaptic transmitter release and regulate neural plasticity. In the present study, whole-cell patch clamp recordings were adopted to examine the activity of TRPV1 Channels in regulating glutamate-mediated excitatory postsynaptic currents (EPSCs) in NAc of rat during morphine withdrawal for 3 days and 3 weeks...
February 7, 2017: Brain Research
https://www.readbyqxmd.com/read/28188220/cannabinoids-activate-monoaminergic-signaling-to-modulate-key-c-elegans-behaviors
#19
Mitchell Oakes, Wen Jing Law, Tobias Clark, Bruce Bamber, Richard Komuniecki
Cannabis or marijuana, a popular recreational drug, alters sensory perception and exerts a range of potential medicinal benefits. The present study demonstrates that the endogenous cannabinoid receptor agonists, 2-arachidonoylglycerol (2-AG) and anandamide (AEA) activate a canonical cannabinoid receptor in C. elegans and also modulate monoaminergic signaling at multiple levels. 2-AG or AEA inhibit nociception and feeding through a pathway requiring the cannabinoid-like receptor, NPR-19. 2-AG or AEA activate NPR-19 directly and cannabinoid-dependent inhibition can be rescued in npr-19 null animals by the expression of a human cannabinoid receptor, CB1, highlighting the orthology of the receptors...
February 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28179879/cannabinoid-receptors-modulate-neuronal-morphology-and-ankyring-density-at-the-axon-initial-segment
#20
Mónica Tapia, Ana Dominguez, Wei Zhang, Ana Del Puerto, María Ciorraga, María José Benitez, Carmen Guaza, Juan José Garrido
Neuronal polarization underlies the ability of neurons to integrate and transmit information. This process begins early in development with axon outgrowth, followed by dendritic growth and subsequent maturation. In between these two steps, the axon initial segment (AIS), a subcellular domain crucial for generating action potentials (APs) and maintaining the morphological and functional polarization, starts to develop. However, the cellular/molecular mechanisms and receptors involved in AIS initial development and maturation are mostly unknown...
2017: Frontiers in Cellular Neuroscience
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