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https://www.readbyqxmd.com/read/28107590/endocannabinoid-activation-of-cb1-receptors-contributes-to-long-lasting-reversal-of-neuropathic-pain-by-repetitive-spinal-cord-stimulation
#1
L Sun, L Tai, Q Qiu, R Mitchell, S Fleetwood-Walker, E A Joosten, C W Cheung
BACKGROUND: Spinal cord stimulation (SCS) has been shown to be effective in the management of certain neuropathic pain conditions, however, the underlying mechanisms are incompletely understood. In this study, we investigated repetitive SCS in a rodent neuropathic pain model, revealing long-lasting and incremental attenuation of hyperalgesia and a mechanism of action involving endocannabinoids. METHOD: Animals were implanted with monopolar electrodes at the time of partial sciatic nerve injury...
January 20, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28106377/chemical-proteomics-maps-brain-region-specific-activity-of-endocannabinoid-hydrolases
#2
Marc P Baggelaar, Annelot van Esbroeck, Eva van Rooden, Bogdan I Florea, Herman S Overkleeft, Giovanni Marsicano, Francis Chaouloff, Mario van der Stelt
The biosynthetic and catabolic enzymes of the endocannabinoids tightly regulate endocannabinoid-mediated activation of the cannabinoid CB1 receptor. Monitoring the activities of these endocannabinoid hydrolases in different brain regions is, therefore, key to gain insight in spatiotemporal control of CB1 receptor-mediated physiology. We have employed a comparative chemical proteomics approach to quantitatively map the activity profile of endocannabinoid hydrolases in various mouse brain regions at the same time...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28104530/long-lasting-alterations-of-hippocampal-gabaergic-neurotransmission-in-adult-rats-following-perinatal-%C3%AE-9-thc-exposure
#3
Sarah Beggiato, Andrea Celeste Borelli, Maria Cristina Tomasini, Lucia Morgano, Tiziana Antonelli, Sergio Tanganelli, Vincenzo Cuomo, Luca Ferraro
The long-lasting effects of gestational cannabinoids exposure on the adult brain of the offspring are still controversial. It has already been shown that pre- or perinatal cannabinoids exposure induces learning and memory disruption in rat adult offspring, associated with permanent alterations of cortical glutamatergic neurotransmission and cognitive deficits. In the present study, the risk of long-term consequences induced by perinatal exposure to cannabinoids on rat hippocampal GABAergic system of the offspring, has been explored...
January 16, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28103941/involvement-of-the-endocannabinoid-system-in-the-physiological-response-to-transient-common-carotid-artery-occlusion-and-reperfusion
#4
Marina Quartu, Laura Poddighe, Tiziana Melis, Maria Pina Serra, Marianna Boi, Sara Lisai, Gianfranca Carta, Elisabetta Murru, Laura Muredda, Maria Collu, Sebastiano Banni
BACKGROUND: The transient global cerebral hypoperfusion/reperfusion achieved by induction of Bilateral Common Carotid Artery Occlusion followed by Reperfusion (BCCAO/R) may trigger a physiological response in an attempt to preserve tissue and function integrity. There are several candidate molecules among which the endocannabinoid system (ECS) and/or peroxisome-proliferator activated receptor-alpha (PPAR-alpha) may play a role in modulating oxidative stress and inflammation. The aims of the present study are to evaluate whether the ECS, the enzyme cyclooxygenase-2 (COX-2) and PPAR-alpha are involved during BCCAO/R in rat brain, and to identify possible markers of the ongoing BCCAO/R-induced challenge in plasma...
January 19, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28102227/singular-location-and-signaling-profile-of-adenosine-a2a-cannabinoid-cb1-receptor-heteromers-in-the-dorsal-striatum
#5
Estefanía Moreno, Anna Chiarlone, Mireia Medrano, Mar Puigdellívol, Lucka Bibic, Lesley A Howell, Eva Resel, Nagore Puente, María J Casarejos, Juan Perucho, Joaquín Botta, Nuria Suelves, Francisco Ciruela, Silvia Ginés, Ismael Galve-Roperh, Vicent Casadó, Pedro Grandes, Beat Lutz, Krisztina Monory, Enric I Canela, Carmen Lluís, Peter J McCormick, Manuel Guzmán
The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A2AR and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A2AR-CB1R heteromeric complexes...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28100841/cannabinoids-a-new-weapon-against-cancer
#6
Małgorzata Pokrywka, Joanna Góralska, Bogdan Solnica
Cannabis has been cultivated by man since Neolithic times. It was used, among others for fiber and rope production, recreational purposes and as an excellent therapeutic agent. The isolation and characterization of the structure of one of the main active ingredients of cannabis - Δ9 - tetrahydrocannabinol as well the discovery of its cannabinoid binding receptors CB1 and CB2, has been a milestone in the study of the possibilities of the uses of Cannabis sativa and related products in modern medicine. Many scientific studies indicate the potential use of cannabinoids in the fight against cancer...
December 29, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100744/compensatory-activation-of-cannabinoid-cb2-receptor-inhibition-of-gaba-release-in-the-rostral-ventromedial-medulla-in-inflammatory-pain
#7
Ming-Hua Li, Katherine L Suchland, Susan L Ingram
: The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain. Endocannabinoids inhibit GABA release in the RVM, but it is not known whether this effect persists in chronic pain states. In the present studies, persistent inflammation induced by complete Freund's adjuvant (CFA) increased GABAergic miniature IPSCs (mIPSCs). Endocannabinoid activation of cannabinoid (CB1) receptors known to inhibit presynaptic GABA release was significantly reduced in the RVM of CFA-treated rats compared with naive rats...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28099629/the-role-of-the-cnr1-gene-in-schizophrenia-a-systematic-review-including-unpublished-data
#8
Eduardo S Gouvêa, Airton F Santos, Vanessa K Ota, Vinicius Mrad, Ary Gadelha, Rodrigo A Bressan, Quirino Cordeiro, Sintia I Belangero
Objective: Schizophrenia is a multifactorial disorder. It is known that a combination of extensive multiple common alleles may be involved in its etiology, each contributing with a small to moderate effect, and, possibly, some rare alleles with a much larger effect size. We aimed to perform a systematic review of association studies between schizophrenia (and its subphenotypes) and polymorphisms in the CNR1 gene, which encodes cannabinoid receptors classically implicated in schizophrenia pathophysiology, as well as to present unpublished results of an association study in a Brazilian population...
January 12, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/28097916/exploring-the-first-rimonabant-analog-opioid-peptide-hybrid-compound-as-bivalent-ligand-for-cb1-and-opioid-receptors
#9
Adriano Mollica, Sveva Pelliccia, Valeria Famiglini, Azzurra Stefanucci, Giorgia Macedonio, Annalisa Chiavaroli, Giustino Orlando, Luigi Brunetti, Claudio Ferrante, Stefano Pieretti, Ettore Novellino, Sandor Benyhe, Ferenc Zador, Anna Erdei, Edina Szucs, Reza Samavati, Szalbolch Dvrorasko, Csaba Tomboly, Rino Ragno, Alexandros Patsilinakos, Romano Silvestri
Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of µ-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects, also at sub-effective doses. In this work, we selected from a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH2...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28087785/thermolytic-degradation-of-synthetic-cannabinoids-chemical-exposures-and-pharmacological-consequences
#10
Brian F Thomas, Timothy W Lefever, Ricardo A Cortes, Alexander L Kovach, Anderson O Cox, Purvi R Patel, Gerald T Pollard, Julie A Marusich, Richard A Kevin, Thomas F Gamage, Jenny L Wiley
Synthetic cannabinoids are manufactured clandestinely with little quality control and are distributed as herbal "Spice" for smoking or as bulk compound for mixing with a solvent and inhalation via electronic vaporizers. Intoxication with synthetic cannabinoids has been associated with seizure, excited delirium, coma, kidney damage, and other disorders. The chemical alterations produced by heating these structurally novel compounds for consumption are largely unknown. Here we show that heating synthetic cannabinoids containing tetramethylcyclopropyl-ring substituents produced thermal degradants with pharmacological activity that varied considerably from their parent compounds...
January 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28087250/pharmacology-of-cannabinoids-in-the-treatment-of-epilepsy
#11
REVIEW
Tyler E Gaston, Daniel Friedman
The use of cannabis products in the treatment of epilepsy has long been of interest to researchers and clinicians alike; however, until recently very little published data were available to support its use. This article summarizes the available scientific data of pharmacology from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including ∆9-tetrahydrocannabinol (∆9-THC), cannabidiol (CBD), ∆9-tetrahydrocannabivarin (∆9-THCV), cannabidivarin (CBDV), and ∆9-tetrahydrocannabinolic acid (Δ9-THCA)...
January 10, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28069688/up-regulation-of-cb2-receptors-in-reactive-astrocytes-in-canine-degenerative-myelopathy-a-disease-model-of-amyotrophic-lateral-sclerosis
#12
María Fernández-Trapero, Francisco Espejo-Porras, Carmen Rodríguez-Cueto, Joan R Coates, Carmen Pérez-Díaz, Eva de Lago, Javier Fernández-Ruiz
Targeting the CB2 receptor afforded neuroprotection in SOD1(G93A) mutant mice, a model of amyotrophic lateral sclerosis (ALS). The neuroprotective effects of CB2 receptors were facilitated by their up-regulation in the spinal cord in SOD1(G93A) mutant mice. Herein, we have investigated whether a similar CB2 receptor up-regulation, as well as parallel changes in other endocannabinoid elements, are evident in the spinal cord of dogs with degenerative myelopathy (DM), caused from mutations in the superoxide dismutase 1 gene (SOD1)...
January 9, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28065722/peripheral-endocannabinoid-signaling-controls-hyperphagia-in-western-diet-induced-obesity
#13
Donovan A Argueta, Nicholas V DiPatrizio
The endocannabinoid system in the brain and periphery plays a major role in controlling food intake and energy balance. We reported that tasting dietary fats was met with increased levels of the endocannabinoids, 2-arachidonoyl-sn-glycerol (2-AG) and anandamide, in the rat upper small intestine, and pharmacological inhibition of this local signaling event dose-dependently blocked sham feeding of fats. We now investigated the contribution of peripheral endocannabinoid signaling in hyperphagia associated with chronic consumption of a western-style diet in mice ([WD] i...
January 5, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28059509/pyrimidinyl-biphenylureas-identification-of-new-lead-compounds-as-allosteric-modulators-of-the-cannabinoid-receptor-cb1
#14
Leepakshi Khurana, Bo-Qiao Fu, Anantha L Duddupudi, Yu-Hsien Liao, Sri Sujana Immadi, Debra A Kendall, Dai Lu
The allosteric modulator 1-(4-chlorophenyl)-3-(3-(6-(pyrrolidin-1-yl)pyridin-2-yl)phenyl)urea (PSNCBAM-1, 2) bound the cannabinoid receptor 1 (CB1) and antagonized G protein coupling. This compound demonstrated potent anorectic effects similar to the CB1 antagonist rimonabant that once was marketed for the treatment of obesity, suggesting a new chemical entity for the discovery of antiobesity drugs. To increase structural diversity of this class of CB1 ligands, we designed and synthesized two classes of novel analogues, in which the pyridine ring of 2 was replaced by a pyrimidine ring...
January 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28025900/phytochemical-and-biological-evaluation-of-salvia-apiana
#15
Radhakrishnan Srivedavyasasri, Taylor Hayes, Samir A Ross
Salvia apiana (white sage, Lamiaceae family) plant is native to southern California and parts of Mexico. Some Native American tribes local to this region consider S. apiana to be sacred and burn the leaves as incense for purification ceremonies. The plant has been used to treat sore throats, coughs, chest colds, upper respiratory infections and poison oak rashes. The aqueous ethanolic extract of S. apiana showed moderate CB1 activity (58.3% displacement). Chromatographic purification of the ethanolic extract on silica gel column led to isolation of nine compounds: rosmadial (I), carnosol (II), 16-hydroxycarnosol (III), sageone (IV), cirsimaritin (V), salvigenin (VI), oleanolic acid (VII), 3β,28-dihydroxy-urs-12-ene (VIII), and ursolic acid (IX)...
December 27, 2016: Natural Product Research
https://www.readbyqxmd.com/read/28017790/the-cb1-receptor-is-required-for-the-establishment-of-the-hyperlocomotor-phenotype-in-developmentally-induced-hypothyroidism-in-mice
#16
Elena Giné, Victor Echeverry-Alzate, Jose Antonio Lopez-Moreno, Fernando Rodriguez de Fonseca, Ana Perez-Castillo, Angel Santos
Alterations in motor functions are well-characterized features observed in humans and experimental animals with thyroid hormone dysfunctions during development. We have previously suggested the implication of the endocannabinoid system in the hyperlocomotor phenotype observed in developmentally induced hypothyroidism in rats. In this work we have further analyzed the implication of endocannabinoids in the effect of hypothyroidism on locomotor activity. To this end, we evaluated the locomotor activity in adult mice lacking the cannabinoid receptor type 1 (CB1R(-/-)) and in their wild type littermates (CB1R(+/+)), whose hypothyroidism was induced in day 12 of gestation and maintained during the experimental period...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28012093/pharmacological-and-toxicological-effects-of-synthetic-cannabinoids-and-their-metabolites
#17
Sherrica Tai, William E Fantegrossi
Commercial preparations containing synthetic cannabinoids (SCBs) are rapidly emerging as drugs of abuse. Although often assumed to be "safe" and "legal" alternatives to cannabis, reports indicate that SCBs induce toxicity not often associated with the primary psychoactive component of marijuana, Δ9-tetrahydrocannabinol (Δ(9)-THC). This chapter will summarize the evidence that use of SCBs poses greater health risks relative to marijuana and suggest that distinct pharmacological properties and metabolism of SCBs relative to Δ(9)-THC may contribute to this increased toxicity...
December 24, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28010996/pharmacological-characterization-of-rat-vd-hemopressin-%C3%AE-an-%C3%AE-hemoglobin-derived-peptide-exhibiting-cannabinoid-agonist-like-effects-in-mice
#18
Ting Zheng, Ting Zhang, Run Zhang, Zi-Long Wang, Zheng-Lan Han, Ning Li, Xu-Hui Li, Meng-Na Zhang, Biao Xu, Xiong-Li Yang, Quan Fang, Rui Wang
Hemopressin and related peptides have shown to function as the endogenous ligands or the regulator of cannabinoid receptors. Moreover, hemopressin and its truncated peptides were also reported to produce a slight modulatory effect on opioid system. In the present work, based on the amino acid sequence analyses of hemoglobin subunit α, rat VD-hemopressin(α) [(r)VD-Hpα] was predicted as a cannabinoid peptide derived from rat α-hemoglobin. Furthermore, (r)VD-Hpα was synthesized and characterized in a series of in vitro and in vivo assays...
December 16, 2016: Neuropeptides
https://www.readbyqxmd.com/read/27999963/identification-of-an-endocannabinoid-system-in-the-rat-pars-tuberalis-a-possible-interface-in-the-hypothalamic-pituitary-adrenal-system
#19
Arsalan Jafarpour, Faramarz Dehghani, Horst-Werner Korf
Endocannabinoids (ECs) are ubiquitous endogenous lipid derivatives and play an important role in intercellular communication either in an autocrine/paracrine or in an endocrine fashion. Recently, an intrinsic EC system has been discovered in the hypophysial pars tuberalis (PT) of hamsters and humans. In hamsters, this EC system is under photoperiodic control and appears to influence the secretion of hormones such as prolactin from the adenohypophysis. We investigate the EC system in the PT of the rat, a frequently used species in endocrine research...
December 20, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27997038/inflammation-of-peripheral-tissues-and-injury-to-peripheral-nerves-induce-diferring-effects-in-the-expression-of-the-calcium-sensitive-anandamide-synthesising-enzyme-and-related-molecules-in-rat-primary-sensory-neurons
#20
João Sousa-Valente, Angelika Varga, Jose Vicente Torres Perez, Agnes Jenes, John Wahba, Ken Mackie, Benjamin Cravatt, Natsuo Ueda, Kazuhito Tsuboi, Peter Santha, Gabor Jancso, Hiren Tailor, António Avelino, Istvan Nagy
Elevation of intracellular Ca(2+) concentration induces the synthesis of N-arachydonoylethanolamine (anandamide) in a sub-population of primary sensory neurons. N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is the only known enzyme, which synthesises anandamide in a Ca(2+) -dependent manner. NAPE-PLD mRNA, as well as anandamide's main targets, the excitatory transient receptor potential vanilloid type 1 ion channel (TRPV1) and the inhibitory cannabinoid type 1 (CB1) receptor and the main anandamide-hydrolysing enzyme fatty acid amide hydrolase (FAAH) are all expressed by sub-populations of nociceptive primary sensory neurons...
December 20, 2016: Journal of Comparative Neurology
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