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Cannabinoid receptors

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https://www.readbyqxmd.com/read/28648984/whole-body-biodistribution-of-the-cannabinoid-type-1-receptor-ligand-18-f-mk-9470-in-the-rat
#1
H G Buchholz, K Uebbing, S Maus, S Pektor, N Afahaene, V Weyer-Elberich, B Lutz, M Schreckenberger, I Miederer
The endocannabinoid system participates in many processes in the body, including memory, reward, pain, motor activity, food intake, energy metabolism, and gastrointestinal functions. [(18)F]MK-9470 is a positron emission tomography (PET) ligand that binds with high affinity and selectivity to the cannabinoid type 1 receptor. In order to fully characterize ligand behavior, tracer uptake measured using in vivo microPET was compared with results from ex vivo tissue dissection. Twelve male Sprague-Dawley rats were divided into three subgroups and scanned over time periods of 10min, 30min and 90min using PET...
June 15, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/28642081/tetrahydrocannabinol-thc-impairs-encoding-but-not-retrieval-of-verbal-information
#2
Mohini Ranganathan, Rajiv Radhakrishnan, Peter H Addy, Ashley Schnakenberg, Ashley Williams, Michelle Carbuto, Jacqueline Elander, Brian Pittman, R Andrew Sewell, Patrick D Skosnik, Deepak Cyril D'Souza
INTRODUCTION: Cannabis and agonists of the brain cannabinoid receptor (CB1R) produce acute memory impairments in humans. However, the extent to which cannabinoids impair encoding and retrieval in humans has not been established. The objective of this analysis was to determine whether the administration of Δ(9)-Tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis, impairs encoding and/or retrieval of verbal information. MATERIALS AND METHODS: Healthy subjects were recruited from the community...
June 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28641517/the-case-for-cannabinoid-cb1-receptors-as-a-target-for-bronchodilator-therapy-for-%C3%AE-agonist-resistant-asthma
#3
John Ashton, Robert J Hancox
Although b2-receceptor agonists are powerful bronchodilators and are at the forefront of asthma symptom relief, patients who use them frequently develop partial resistance to them. This can be a particularly serious problem during severe attacks, where high dose b2-agonist treatment is the front line therapy. Alternative bronchodilators are urgently needed. In this article we review the evidence for the bronchodilator effects of the cannabinoid CB1 receptor tetrahydrocannabinol (THC) and suggest that the mechanism of action for these effects are sufficiently independent of the mechanisms of standard bronchodilators to warrant clinical investigation...
June 15, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28641496/guanfacine-attenuates-adverse-effects-of-dronabinol-thc-on-working-memory-in-adolescent-onset-heavy-cannabis-users-a-pilot-study
#4
David S Mathai, Manuela Holst, Christopher Rodgman, Colin N Haile, Jake Keller, Mariyah Z Hussain, Thomas R Kosten, Thomas F Newton, Christopher D Verrico
The cannabinoid-1 receptor (CB1R) agonist Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, adversely effects working memory performance in humans. The α2A-adrenoceptor (AR) agonist guanfacine improves working memory performance in humans. The authors aimed to determine the effects of short-term (6 days) treatment with guanfacine on adverse cognitive effects produced by THC. Employing a double-blind, placebo-controlled crossover design, the cognitive, subjective, and cardiovascular effects produced by oral THC (20 mg) administration were determined twice in the same cannabis users: once after treatment with placebo and once after treatment with guanfacine (3 mg/day)...
June 23, 2017: Journal of Neuropsychiatry and Clinical Neurosciences
https://www.readbyqxmd.com/read/28638091/the-cannabinoid-ligand-lh-21-reduces-anxiety-and-improves-glucose-handling-in-diet-induced-obese-pre-diabetic-mice
#5
Silvana Y Romero-Zerbo, Inmaculada Ruz-Maldonado, Vanesa Espinosa-Jiménez, Alex Rafacho, Ana I Gómez-Conde, Lourdes Sánchez-Salido, Nadia Cobo-Vuilleumier, Benoit R Gauthier, Francisco J Tinahones, Shanta J Persaud, Francisco J Bermúdez-Silva
LH-21 is a triazol derivative that has been described as a low-permeant neutral CB1 antagonist, though its pharmacology is still unclear. It has been associated with anti-obesity actions in obese rats. However, its role in preventing type 2 diabetes (T2D) onset have not been studied yet. Given CB1 receptors remain as potential pharmacological targets to fight against obesity and T2D, we wanted to explore the metabolic impact of this compound in an animal model of obesity and pre-diabetes as well as the lack of relevant actions in related central processes such as anxiety...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28635664/adolescent-exposure-to-the-synthetic-cannabinoid-win-55212-2-modifies-cocaine-withdrawal-symptoms-in-adult-mice
#6
María A Aguilar, Juan Carlos Ledesma, Marta Rodríguez-Arias, Carles Penalva, Carmen Manzanedo, José Miñarro, M Carmen Arenas
Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from it can cause psychiatric symptoms, such as psychosis, cognitive impairment, anxiety, and depression. The aim of the present research was to study the consequences of adolescent exposure to cannabis on the psychiatric-like effects promoted by cocaine withdrawal in adult mice...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28629846/hippocampal-gr-and-cb1-mediated-mglur5-differentially-produces-susceptibility-and-resilience-to-acute-and-chronic-mild-stress-in-rats
#7
Hongli Sun, Rujuan Su, Xiaoxiao Zhang, Jun Wen, Dan Yao, Xinru Gao, Zhongliang Zhu, Hui Li
The molecular mechanism of individual response of susceptibility and resilience under psychological stress remains controversial and unclear. The present study aimed to explore the relationship of metabotropic glutamate receptor 5 (mGluR5) with glucocorticoid receptor (GR) or cannabinoid receptor (CB1) and further indicate the molecular mechanism of susceptibility and resilience to acute stress (AS) and chronic mild stress (CMS). Sucrose preference test and open field test were used to evaluate the response of susceptibility and resilience under stress in rats...
June 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28629227/chemical-and-biological-studies-on-cichorium-intybus-l
#8
Dinara Satmbekova, Radhakrishnan Srivedavyasasri, Yerkebulan Orazbekov, Roza Omarova, Ubaidilla Datkhayev, Samir A Ross
Cichorium intybus L. (Asteraceae family) is a world-wide grown plant known as chicory. In traditional medicine, this plant is used as diuretic, anti-inflammatory, digestive, cardiotonic and liver tonic. Chromatographic purification of the supercritical fluid extract of aerial parts of C. intybus on silica gel column led to isolation of three compounds: new compound, 28β-hydroxytaraxasterol (I), and two known compounds usnic acid (II) and β-sitosterol (III). Purification of the ethanolic extract of aerial parts of this plant on silica gel column chromatography yielded four compounds: 1,3-dioleylglycerate (IV), sitoindoside II (V), 11β-13-dihydrolactucin (VI) and β-sitosterol-3-O-glucoside (VII)...
June 19, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28626532/development-of-quinazoline-pyrimidine-2-4-1h-3h-diones-as-agonists-of-cannabinoid-receptor-type-2
#9
Hai-Yan Qian, Zhi-Long Wang, You-Lu Pan, Li-Li Chen, Xin Xie, Jian-Zhong Chen
Starting from a prototypical structure 1, we describe our efforts to design and obtain novel quinazoline/pyrimidine-2,4(1H,3H)-diones with high CB2 agonist potency and selectivity as well as improved physicochemical characteristics, mainly hydrophilicity. The most potent and selective CB2 agonists, 8 and 36, in this series were also endowed with lower logP values than that of GW842166X and lead compound 1. These derivatives appear to be promising lead compounds for the development of future CB2 agonists.
June 8, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28625718/synaptic-functions-of-endocannabinoid-signaling-in-health-and-disease
#10
REVIEW
Alfonso Araque, Pablo E Castillo, Olivier J Manzoni, Raffaella Tonini
Endocannabinoids (eCBs) are a family of lipid molecules that act as key regulators of synaptic transmission and plasticity. They are synthetized "on demand" following physiological and/or pathological stimuli. Once released from postsynaptic neurons, eCBs typically act as retrograde messengers to activate presynaptic type 1 cannabinoid receptors (CB1) and induce short- or long-term depression of neurotransmitter release. Besides this canonical mechanism of action, recent findings have revealed a number of less conventional mechanisms by which eCBs regulate neural activity and synaptic function, suggesting that eCB-mediated plasticity is mechanistically more diverse than anticipated...
June 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28624572/role-of-beta-catenin-and-endocannabinoids-in-the-nucleus-accumbens-in-extinction-in-rats-exposed-to-shock-and-reminders
#11
Nachshon Korem, Rachel Lange, Cecilia J Hillard, Irit Akirav
The response to a traumatic experience may be rapid recovery or development of psychopathology such as post-traumatic stress disorder (PTSD). Impaired extinction of fear memories is thought to contribute to the development of the persistent trauma memories and avoidance. The Wnt/β-catenin pathway and the endocannabinoid system appear to play significant roles in anxiety and depressive symptoms. Here we examined the involvement of β-catenin in the nucleus accumbens (NAc) in extinction in rats exposed to the shock and reminders model of PTSD...
June 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28624517/intra-accumbal-blockade-of-endocannabinoid-cb1-receptors-impairs-learning-but-not-retention-of-conditioned-relief
#12
Jorge R Bergado Acosta, Miriam Schneider, Markus Fendt
Humans and animals are able to associate an environmental cue with the feeling of relief from an aversive event, a phenomenon called relief learning. Relief from an aversive event is rewarding and a relief-associated cue later induces an attenuation of the startle magnitude or approach behavior. Previous studies demonstrated that the nucleus accumbens is essential for relief learning. Here, we asked whether accumbal cannabinoid type 1 (CB1) receptors are involved in relief learning. In rats, we injected the CB1 receptor antagonist/inverse agonist SR141716A (rimonabant) directly into the nucleus accumbens at different time points during a relief learning experiment...
June 15, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28624443/inhibitory-effect-of-trans-caryophyllene-tc-on-leukocyte-endothelial-attachment
#13
Zhen Zhang, Chunfeng Yang, Xinlun Dai, Yu Ao, Yumei Li
trans-Caryophyllene (TC) is a major component found in the essential oils of many spices and foods/medicinal plants. It is a natural sesquiterpene and has been the subject of numerous studies. However, the effects of TC on vascular inflammation remain unknown. In this study, we reported that TC treatment in human umbilical vein endothelial cells (HUVECs) prevented attachment of monocytic leukemia cell line THP-1 cells to endothelial cells. In addition, in vivo results indicate that TC inhibited macrophage infiltration to the aortic surface and reduced total serum levels of cholesterol and triglycerides...
June 14, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28619471/oral-haloperidol-or-olanzapine-intake-produces-distinct-and-region-specific-increase-in-cannabinoid-receptor-levels-that-is-prevented-by-high-fat-diet
#14
Foteini Delis, Lauren Rosko, Aditya Schroff, Kenneth E Leonard, Panayotis K Thanos
Clinical studies show higher levels of cannabinoid CB1 receptors (CB1R) in the brain of schizophrenic patients while preclinical studies report a significant functional interaction between dopamine D2 receptors and CB1Rs as well as an upregulation of CB1Rs after antipsychotic treatment. These findings prompted us to study the effects of chronic oral intake of a first and a second generation antipsychotic, haloperidol and olanzapine, on the levels and distribution of CB1Rs in the rat brain. Rats consumed either regular chow or high-fat food and drank water, haloperidol drinking solution (1...
June 12, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28618070/morin-suppresses-astrocyte-activation-and-regulates-cytokine-release-in-bone-cancer-pain-rat-models
#15
Wei Jiang, Ying Wang, Wei Sun, Mengyuan Zhang
As inflammatory and immune responses are involved in pathophysiology of debilitating neuropathic pain, reagents that can modulate these two responses may have therapeutic potential. Morin, derived from the moraceae family of plants, benefits inflammation-related diseases, but its antinociceptive effects on cancer pain remain elusive. In the present study, we investigated antinociceptive effects of morin on bone cancer pain using a rat model, where rats were subject to implantation of Walker 256 mammary gland carcinoma cells into the tibia...
June 15, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28610718/echinacea-purpurea-derived-alkylamides-exhibit-potent-anti-inflammatory-effects-and-alleviate-clinical-symptoms-of-atopic-eczema
#16
Attila Oláh, Judit Szabó-Papp, Michael Soeberdt, Ulrich Knie, Stephan Dähnhardt-Pfeiffer, Christoph Abels, Tamás Bíró
BACKGROUND: Atopic eczema (AE) is a chronic inflammatory and pruritic skin disease. There is still an unmet need for topical anti-inflammatory and anti-pruritic substances exhibiting an excellent safety profile. The endocannabinoid system is known to regulate various aspects of cutaneous barrier and immune functions, thus targeting it may be a valid approach for alleviating the symptoms of AE. OBJECTIVE: To assess the putative efficacy of Echinacea purpurea-derived alkylamides (Ec...
May 27, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28608697/perspectives-of-cannabinoid-type-2-receptor-cb2r-ligands-in-neurodegenerative-disorders-structure-affinity-relationship-safir-and-structure-activity-relationship-sar-studies
#17
Francesco Spinelli, Elena Capparelli, Carmen Abate, Nicola A Colabufo, Marialessandra Contino
Up-regulation of CB2R on activated microglial cells, the first step in neurodegeneration, has been widely demonstrated, and this finding makes the receptor a promising target in the early diagnosis and treatment of several neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS). The development of CB2R PET ligands could help demonstrate the neurodegenerative pathogenesis, thus providing useful tools for characterizing the role of neuroinflammation in the progression of these disorders...
June 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28608560/endocannabinoid-system-in-neurodegenerative-disorders
#18
REVIEW
Balapal S Basavarajappa, Madhu Shivakumar, Vikram Joshi, Shivakumar Subbanna
Most neurodegenerative disorders (NDDs) are characterized by cognitive impairment and other neurological defects. The definite cause of and pathways underlying the progression of these NDDs are not well defined. Several mechanisms have been proposed to contribute to the development of NDDs. These mechanisms may proceed concurrently or successively, and they differ among cell types at different developmental stages in distinct brain regions. The endocannabinoid system, which involves cannabinoid receptors type 1 (CB1R) and type 2 (CB2R), endogenous cannabinoids and the enzymes that catabolize these compounds, has been shown to contribute to the development of NDDs in several animal models and human studies...
June 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28608535/discovery-and-characterization-of-two-novel-cb1-receptor-splice-variants-with-modified-n-termini-in-mouse
#19
Sabine Ruehle, James Wager-Miller, Alex Straiker, Jill Farnsworth, Michelle N Murphy, Sebastian Loch, Krisztina Monory, Ken Mackie, Beat Lutz
Numerous studies have been carried out in the mouse model, investigating the role of the CB1 cannabinoid receptor. However, mouse CB1 (mCB1) receptor differs from human CB1 (hCB1) receptor in 13 amino acid residues. Two splice variants, hCB1a and hCB1b, diverging in their amino-termini, have been reported to be unique for hCB1 and, via different signaling properties, contribute to CB1 receptor physiology and pathophysiology. We hypothesized that splice variants also exist for the mCB1 receptor and have different signaling properties...
June 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28607917/thrombotic-microangiopathy-associated-with-synthetic-cannabinoid-receptor-agonists
#20
Michael Karass, Savneek Chugh, Gabriela Andries, Aleksandra Mamorska-Dyga, John C Nelson, Praveen N Chander
Marijuana is one of the most commonly used recreational drugs in the United States. As marijuana is illegal in the majority of countries, the use of readily available and unregulated synthetic cannabinoids (SCBs) has increased. Little is known about the potential adverse effects of SCBs especially in regards to their nephrotoxicity. Case reports of acute kidney injury (AKI) from acute tubular injury secondary to their use have been reported. However, the exact pathology, mechanism, and extent of renal injury remain unknown...
2017: Stem Cell Investigation
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