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Endocannabinoid system

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https://www.readbyqxmd.com/read/28822686/the-role-of-human-monoacylglycerol-lipase-hmagl-binding-pocket-in-breakup-of-unsaturated-phospholipid-membranes
#1
Ioannis Karageorgos, Vitalii I Silin, Nikolai Zvonok, John Marino, David R Janero, Alexandros Makriyannis
Human monoacylglycerol lipase (hMAGL) plays a key role in homeostatic tuning of the endocannabinoid signaling system and supports aggressive tumorogenesis, making this enzyme a promising therapeutic target. hMAGL features a membrane-associated lid domain that regulates entry of endocannabinoid lipid substrates into the hydrophobic channel accessing the active site, likely from the membrane bilayer. The present work applied simultaneous surface plasmon resonance and electrochemical impedance spectroscopy measurements to show that, in absence of the substrate, hMAGL can remove phospholipid molecules from the membrane and, thereby, disintegrate pre-formed, intact, tethered phospholipid bilayer membrane mimetics (tBLMs) composed of unsaturated phosphatidylcholines...
August 16, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28818702/the-effects-of-cannabinoid-receptors-activation-and-glucocorticoid-receptors-deactivation-in-the-amygdala-and-hippocampus-on-the-consolidation-of-a-traumatic-event
#2
Noa Shoshan, Irit Akirav
Ample evidence demonstrates that fear learning contributes significantly to many anxiety pathologies including post-traumatic stress disorder (PTSD). The endocannabinoid (eCB) system may offer therapeutic benefits for PTSD and it is a modulator of the hypothalamic pituitary adrenal (HPA) axis. Here we compared the separated and combined effects of blocking glucocorticoid receptors (GRs) using the GR antagonist RU486 and enhancing CB1r signaling using the CB1/2 receptor agonist WIN55,212-2 in the CA1 and basolateral amygdala (BLA) on the consolidation of traumatic memory...
August 14, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28818631/topical-medical-cannabis-tmc-a-new-treatment-for-wound-pain-three-cases-of-pyoderma-gangrenosum
#3
Vincent Maida, Jason Corban
Pain associated with integumentary wounds is highly prevalent yet it remains an area of significant unmet need within healthcare. Currently, systemically administered opioids are the mainstay of treatment. However, recent publications are casting opioids in a negative light given their high side effect profile, inhibition of wound healing, and association with accidental overdose, incidents that are frequently fatal. Thus, novel analgesic strategies for wound-related pain need to be investigated. The ideal methods of pain relief for wound patients are modalities that are topical, lack systemic side effects, non-invasive, self-administered, and display rapid onset of analgesia...
August 14, 2017: Journal of Pain and Symptom Management
https://www.readbyqxmd.com/read/28816506/inhibition-of-monoacylglycerol-lipase-another-signalling-pathway-for-potential-therapeutic-targets-in-migraine
#4
Rosaria Greco, Chiara Demartini, Anna Maria Zanaboni, Laura Berliocchi, Daniele Piomelli, Cristina Tassorelli
Background Drugs that modulate endocannabinoid signalling are effective in reducing nociception in animal models of pain and may be of value in the treatment of migraine. Methods We investigated the anti-nociceptive effects of inhibition of monoacylglycerol lipase (MGL), a key enzyme in the hydrolysis of the 2-arachidonoylglycerol, in a rat model of migraine based on nitroglycerin (NTG) administration. We evaluated c-fos expression in specific brain areas and nociceptive behavior in trigeminal and extra-trigeminal body areas...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/28816239/hippocampal-protein-kinase-c-signaling-mediates-the-short-term-memory-impairment-induced-by-delta9-tetrahydrocannabinol
#5
Arnau Busquets-Garcia, Maria Gomis-González, Victòria Salgado-Mendialdúa, Lorena Galera-López, Emma Puighermanal, Elena Martín-García, Rafael Maldonado, Andrés Ozaita
Cannabis affects cognitive performance through the activation of the endocannabinoid system, and the molecular mechanisms involved in this process are poorly understood. Using the novel object-recognition memory test in mice, we found that the main psychoactive component of cannabis, delta9-tetrahydrocannabinol (THC), alters short-term object-recognition memory specifically involving protein kinase C (PKC)-dependent signaling. Indeed, the systemic or intra-hippocampal pre-treatment with the PKC inhibitors, prevented the short-term, but not the long-term, memory impairment induced by THC...
August 17, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28811049/marijuana-and-cannabinoids-in-esrd-and-earlier-stages-of-ckd
#6
Joshua L Rein, Christina M Wyatt
Marijuana is the most commonly used recreational drug in the United States, and legal recreational and medicinal use has gained public acceptance during the last decade. Twenty-nine US states have established medical marijuana programs, 8 of which have also legalized recreational marijuana, and Canada is expected to legalize recreational marijuana in 2018. Advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) are chronic conditions with significant associated morbidity and mortality. Patients experience substantial symptom burden that is frequently undertreated due to adverse medication side effects...
August 12, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28799775/a-review-of-the-therapeutic-antitumor-potential-of-cannabinoids
#7
Višnja Bogdanović, Jasminka Mrdjanović, Ivana Borišev
OBJECTIVES: The aim of this review is to discuss cannabinoids from a preclinical and clinical oncological perspective and provide the audience with a concise, retrospective overview of the most significant findings concerning the potential use of cannabinoids in cancer treatment. METHODS: A literature survey of medical and scientific databases was conducted with a focus on the biological and medical potential of cannabinoids in cancer treatment. RESULTS: Cannabis sativa is a plant rich in more than 100 types of cannabinoids...
August 11, 2017: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
https://www.readbyqxmd.com/read/28799288/neuroprotective-activity-of-cannabinoid-receptor-2-against-oxidative-stress-and-apoptosis-in-rat-pups-having-experimentally-induced-congenital-hypothyroidism
#8
Mehmet Eray Alcigir, Halef Okan Dogan, Sevil Atalay Vural, Fatma Meriç Yilmaz
In this study, it was aimed to show the cannabinoid receptor-2 (CB2) role, which is a part of neuroprotective endocannabinoidal system, against increasing nitric oxide synthetase (iNOS, eNOS) levels and the apoptotic activity (caspase-3, caspase-9 and DNA in situ fragmentation) within the postnatal critical period in pups of pregnant rats with artificially induced maternal thyroid hormone (TH) deficiency. Each of the 3 groups established comprised 1 male and 2 female rats, and they were coupled. Their pups were used...
August 11, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28790443/endocannabinoid-tone-is-higher-in-healthy-lean-south-asian-than-white-caucasian-men
#9
Vasudev Kantae, Kimberly J Nahon, Maaike E Straat, Leontine E H Bakker, Amy C Harms, Mario van der Stelt, Thomas Hankemeier, Ingrid M Jazet, Mariëtte R Boon, Patrick C N Rensen
South Asians have a higher risk to develop obesity and related disorders compared to white Caucasians. This is likely in part due to their lower resting energy expenditure (REE) as related with less energy-combusting brown adipose tissue (BAT). Since overactivation of the endocannabinoid system is associated with obesity and low BAT activity, we hypothesized that South Asians have a higher endocannabinoid tone. Healthy lean white Caucasian (n = 10) and South Asian (n = 10) men were cold-exposed to activate BAT...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768662/stimulation-of-diuresis-and-natriuresis-by-renomedullary-infusion-of-a-dual-inhibitor-of-fatty-acid-amide-hydrolase-and-monoacylglycerol-lipase
#10
Ashfaq Ahmad, Zdravka Daneva, Guangbi Li, Sara K Dempsey, Ningjun Li, Justin Poklis, Aron Lichtman, Pin-Lan Li, Joseph Kraft Ritter
The renal medulla, considered critical for the regulation of salt and water balance and long-term blood pressure control, is enriched in anandamide and two of its major metabolizing enzymes, cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH). Infusion of anandamide (15, 30 and 60 nmol/min/kg) into the renal medulla of C57BL/6J mice stimulated diuresis and salt excretion in a COX-2- but not COX-1-dependent manner. To determine if endogenous endocannabinoids in the renal medulla can elicit similar effects, the effects of intramedullary isopropyl dodecyl fluorophosphate (IDFP), which inhibits the two major endocannabinoid hydrolases, were studied...
August 2, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28767505/age-dependent-plasticity-in-endocannabinoid-modulation-of-pain-processing-through-postnatal-development
#11
Charlie H-T Kwok, Ian M Devonshire, Amer Imraish, Charles M Greenspon, Stevie Lockwood, Catherine Fielden, Andrew Cooper, Stephen Woodhams, Sarir Sarmad, Catherine A Ortori, David A Barrett, David Kendall, Andrew J Bennett, Victoria Chapman, Gareth J Hathway
Significant age and experience-dependent remodelling of spinal and supraspinal neural networks occur resulting in altered pain responses in early life. In adults endogenous opioid peptide and endocannabinoid (ECs) pain control systems exist which modify pain responses but the role they play in acute responses to pain and postnatal neurodevelopment is unknown. Here we have studied the changing role of the ECs in brainstem nuclei essential for the control of nociception from birth to adulthood in both rat and human...
August 1, 2017: Pain
https://www.readbyqxmd.com/read/28764155/role-of-endocannabinoids-on-neuroinflammation-in-autism-spectrum-disorder-prevention
#12
REVIEW
Syed Shahid Habib, Khalid Al-Regaiey, Shahid Bashir, Muhammad Iqbal
Autism Spectrum Disorder (ASD) disease has become a mounting socio-economical alarm around the world. Neuroinflammtion had been shown in postmortem brain specimens from ASD patients. The Endocannabinoids System (ES) consists of a family of locally produced, short-lived, endogenous, phospholipid-derived agonists (endocannabinoids) that control energy balance and body composition. The growing number of medical benefits of ES, such as their ability to regulate processes like neuroinflammation, neurogenesis and memory, raise the question of their potential role as a preventive treatment of ASD...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28759733/protective-effect-of-rimonabant-a-canabinoid-receptor-1-antagonist-on-nonalcoholic-fatty-liver-disease-in-a-rat-model-by-modulating-the-hepatic-expression-of-activin-a-and-follistatin
#13
Noha Ibrahim Hussien, Hanan I El-Kerdasy, Mohamed El-Tantawy Ibrahim
Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver morbidity and mortality with no proven effective therapy yet. Endocannabinoid system plays an important role in various liver diseases. Activin A is a member of the transforming growth factor beta (TGF-β) superfamily and inhibits hepatocyte growth. Follistatin antagonizes the biological actions of activin A. The present study was designed to investigate the effect of rimonabant (a potent cannabinoid receptor1 (CB1) antagonist) on NAFLD induced by choline deficient (CD) diet in rats, as well as to detect whether it can modulate the hepatic expression of activin A and follistatin or not...
July 31, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28758944/interactions-between-the-kynurenine-and-the-endocannabinoid-system-with-special-emphasis-on-migraine
#14
REVIEW
Gábor Nagy-Grócz, Ferenc Zádor, Szabolcs Dvorácskó, Zsuzsanna Bohár, Sándor Benyhe, Csaba Tömböly, Árpád Párdutz, László Vécsei
Both the kynurenine and the endocannabinoid systems are involved in several neurological disorders, such as migraine and there are increasing number of reports demonstrating that there are interactions of two systems. Although their cooperation has not yet been implicated in migraine, there are reports suggesting this possibility. Additionally, the individual role of the endocannabinoid and kynurenine system in migraine is reviewed here first, focusing on endocannabinoids, kynurenine metabolites, in particular kynurenic acid...
July 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28756656/targeting-fatty-acid-amide-hydrolase-with-prodrugs-for-cns-selective-therapy
#15
J Matthew Meinig, Skylar J Ferrara, Tania Banerji, Tapasree Banerji, Hannah S Sanford-Crane, Dennis Bourdette, Thomas S Scanlan
The blood-brain barrier (BBB) can be a substantial impediment to achieving therapeutic levels of drugs in the CNS. Certain chemical functionality such as the carboxylic acid is a general liability for BBB permeability preventing significant CNS distribution of a drug from a systemic dose. Here, we report a novel strategy for CNS-selective distribution of the carboxylic acid containing thyromimetic sobetirome using prodrugs targeted to fatty-acid amide hydrolase (FAAH), which is expressed in the brain. Two amide prodrugs of sobetirome were shown to be efficient substrates of FAAH with Vmax/KM values comparable to the natural endocannabinoid FAAH substrate anandamide...
July 30, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28754373/cannabidiol-disrupts-the-consolidation-of-specific-and-generalized-fear-memories-via-dorsal-hippocampus-cb1-and-cb2-receptors
#16
Cristina A J Stern, Thiago R da Silva, Ana M Raymundi, Camila P de Souza, Vinicius A Hiroaki-Sato, Luiza Kato, Francisco S Guimarães, Roberto Andreatini, Reinaldo N Takahashi, Leandro J Bertoglio
Pharmacological interventions able to modulate a fear memory while it is consolidated could have therapeutic value in tempering those maladaptively overconsolidated. Animal and human studies have shown the intensity of unconditioned stimulus delivered during fear conditioning influences qualitative and quantitative aspects of the memory to be established. By varying the shock intensity used for contextual pairing in rats, here we induced specific and more generalized long-term fear memories to investigate whether, how and where in the brain the cannabidiol (CBD; 3...
July 25, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28752643/combined-deficiency-of-the-cnr1-and-cnr2-receptors-protects-against-age-related-bone-loss-by-osteoclast-inhibition
#17
Antonia Sophocleous, Silvia Marino, Dilruba Kabir, Stuart H Ralston, Aymen I Idris
The endocannabinoid system plays a role in regulating bone mass and bone cell activity and inactivation of the type 1 (Cnr1) or type 2 (Cnr2) cannabinoid receptors influences peak bone mass and age-related bone loss. As the Cnr1 and Cnr2 receptors have limited homology and are activated by different ligands, we have evaluated the effects of combined deficiency of Cnr1 and 2 receptors (Cnr1/2(-/-) ) on bone development from birth to old age and studied ovariectomy induced bone loss in female mice. The Cnr1/2(-/-) mice had accelerated bone accrual at birth when compared with wild type littermates, and by 3 months of age, they had higher trabecular bone mass...
July 28, 2017: Aging Cell
https://www.readbyqxmd.com/read/28750817/endocannabinoid-transport-proteins-discovery-of-tools-to-study-sterol-carrier-protein-2
#18
Cecilia J Hillard, Huan Huang, Caleb D Vogt, Beatriz E Rodrigues, Terrence S Neumann, Daniel S Sem, Friedhelm Schroeder, Christopher W Cunningham
The endocannabinoid (eCB) neurotransmitter system regulates diverse neurological functions including stress and anxiety, pain, mood, and reward. Understanding the mechanisms underlying eCB regulation is critical for developing targeted pharmacotherapies to treat these and other neurologic disorders. Cellular studies suggest that the arachidonate eCBs, N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), are substrates for intracellular binding and transport proteins, and several candidate proteins have been identified...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28750816/techniques-for-the-cellular-and-subcellular-localization-of-endocannabinoid-receptors-and-enzymes-in-the-mammalian-brain
#19
Luigia Cristino, Roberta Imperatore, Vincenzo Di Marzo
This chapter attempts to piece together knowledge about new advanced microscopy techniques to study the neuroanatomical distribution of endocannabinoid receptors and enzymes at the level of cellular and subcellular structures and organelles in the brain. Techniques ranging from light to electron microscopy up to the new advanced LBM, PALM, and STORM super-resolution microscopy will be discussed in the context of their contribution to define the spatial distribution and organization of receptors and enzymes of the endocannabinoid system (ECS), and to better understand ECS brain functions...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28750812/expression-and-nmr-structural-studies-of-isotopically-labeled-cannabinoid-receptor-type-ii
#20
Alexei Yeliseev, Klaus Gawrisch
Cannabinoid receptor type II (CB2) is an integral membrane protein with seven transmembrane helices that belongs to the large superfamily of rhodopsin-like G protein-coupled receptors. The CB2 is a part of the endocannabinoid system that plays a vital role in regulation of immune response, inflammation, pain, and other metabolic processes. Information about the structure and function of CB2 in cell membranes is essential for development of specific pharmaceuticals that target CB2 signaling. Methodology for recombinant expression, stable isotope labeling, purification, reconstitution into liposomes, and NMR characterization of functionally active CB2 is presented...
2017: Methods in Enzymology
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