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https://www.readbyqxmd.com/read/28404744/the-role-of-cb1-in-intestinal-permeability-and-inflammation
#1
Mustafa A Karwad, Daniel G Couch, Elena Theophilidou, Sarir Sarmad, David A Barrett, Michael Larvin, Karen L Wright, Jonathan N Lund, Saoirse E O'Sullivan
The endocannabinoid system has previously been shown to play a role in the permeability and inflammatory response of the human gut. The goal of our study was to determine the effects of endogenous anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) on the permeability and inflammatory response of intestinal epithelium under normal, inflammatory, and hypoxic conditions. Human intestinal mucosa was modeled using Caco-2 cells. Human tissue was collected from planned colorectal resections. Accumulation of AEA and 2-AG was achieved by inhibiting their metabolizing enzymes URB597 (a fatty acid amide hydrolase inhibitor) and JZL184 (a monoacylglycerol lipase inhibitor)...
April 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28404451/anandamide-and-2-ag-are-endogenously-present-within-the-laterodorsal-tegmental-nucleus-functional-implications-for-a-role-of-ecbs-in-arousal
#2
Neeraj Soni, Bala Krishna Prabhala, Ved Mehta, Osman Mirza, Kristi Anne Kohlmeier
Previously, we presented electrophysiological evidence for presence in mice brain slices of functional cannabinoid type I receptors (CB1Rs) within the laterodorsal tegmentum (LDT), a brain stem nucleus critical in control of arousal and rapid eye movement (REM) sleep. Further, using pharmacological agents, we provided data suggestive of the endogenous presence of cannabinoids (CBs) acting at LDT CB1Rs. However, in those studies, we were unable to identify the type(s) of CB ligands endogenously present in the LDT, and this information has not been provided elsewhere...
April 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28389107/ceramide-binding-to-anandamide-increases-its-half-life-and-potentiates-its-cytotoxicity-in-human-neuroblastoma-cells
#3
Coralie Di Scala, Morgane Mazzarino, Nouara Yahi, Karine Varini, Nicolas Garmy, Jacques Fantini, Henri Chahinian
Anandamide (AEA) is a ubiquitous lipid that exerts neurotransmitter functions but also controls important biological functions such as proliferation, survival, or programmed cell death. The latter effects are also regulated by ceramide, a lipid enzymatically generated from sphingomyelin hydrolysis by sphingomyelinase. Ceramide has been shown to increase the cellular toxicity of AEA, but the mechanisms controlling this potentiating effect remained unclear. Here we have used a panel of in silico, physicochemical, biochemical and cellular approaches to study the crosstalk between AEA and ceramide apoptotic pathways...
April 4, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28356298/activation-of-cb1-receptors-by-2-arachidonoylglycerol-attenuates-vasoconstriction-induced-by-u46619-and-angiotensin-ii-in-human-and-rat-pulmonary-arteries
#4
Olga Karpińska, Marta Baranowska-Kuczko, Monika Kloza, Ewa Ambrożewicz, Tomasz Kozłowski, Irena Kasacka, Barbara Malinowska, Hanna Kozłowska
Recent evidence suggests that endocannabinoids acting via cannabinoid CB1 receptors may modulate vascular responses of various vasoconstrictors in the rodent systemic vasculature. The aim of the study was to investigate whether endocannabinoids modulate the contractile responses evoked by a thromboxane A2 analog (U46619), angiotensin II (Ang II), serotonin (5-HT) and phenylephrine which stimulate distinct Gq/11-protein coupled receptors (TP, AT1, 5-HT2 and α1-adrenergic) in isolated endothelium-intact human (hPAs) and rat pulmonary arteries (rPAs)...
March 29, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28346523/a-moderate-diet-restriction-during-pregnancy-alters-the-levels-of-endocannabinoids-and-endocannabinoid-related-lipids-in-the-hypothalamus-hippocampus-and-olfactory-bulb-of-rat-offspring-in-a-sex-specific-manner
#5
María Teresa Ramírez-López, Mariam Vázquez, Ermelinda Lomazzo, Clementine Hofmann, Rosario Noemi Blanco, Francisco Alén, María Antón, Juan Decara, Rocío Arco, Laura Orio, Juan Suárez, Beat Lutz, Raquel Gómez de Heras, Laura Bindila, Fernando Rodríguez de Fonseca
Undernutrition during pregnancy has been associated to increased vulnerability to develop metabolic and behavior alterations later in life. The endocannabinoid system might play an important role in these processes. Therefore, we investigated the effects of a moderate maternal calorie-restricted diet on the levels of the endocannabinoid 2-arachidonoyl glycerol (2-AG), arachidonic acid (AA) and the N-acylethanolamines (NAEs) anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) in the brain of newborn rat offspring...
2017: PloS One
https://www.readbyqxmd.com/read/28337718/sex-dependent-effects-of-neonatal-maternal-deprivation-on-endocannabinoid-levels-in-the-adipose-tissue-influence-of-diet
#6
Virginia Mela, Fabiana Piscitelli, Alvaro Llorente Berzal, Julie Chowen, Cristoforo Silvestri, Maria Paz Viveros, Vincenzo Di Marzo
Maternal deprivation (MD) during neonatal life has diverse long-term effects, including modification of metabolism. We have previously reported that MD modifies the metabolic response to high-fat diet (HFD) intake, with this response being different between males and females, while previous studies indicate that in mice with HFD-induced obesity, endocannabinoid (EC) levels are markedly altered in various brown and white adipose tissue depots. Here, we analyzed the effects of MD (24 h at postnatal day 9), alone or in combination with a HFD from weaning until the end of the experiment in Wistar rats of both sexes...
March 23, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28337517/a-column-switching-ultrahigh-performance-liquid-chromatography-tandem-mass-spectrometry-method-to-determine-anandamide-and-2-arachidonoylglycerol-in-plasma-samples
#7
Camila Marchioni, Israel Donizeti de Souza, Caroline Fernandes Grecco, José Alexandre Crippa, Vitor Tumas, Maria Eugênia Costa Queiroz
This study reports a fast, sensitive, and selective column switching ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine the endocannabinoids (eCBs), anandamide (AEA), and 2-arachidonoylglycerol (2-AG) in plasma samples. This bidimensional system used a restricted access media column (RP-8 ADS, 25 mm × 4 mm × 25 μM) in the first dimension and a core-shell Kinetex C18 (100 mm × 2, 1.7 mm × 1 μM) column in the second dimension, followed by detection in a mass spectrometer triple quadrupole (multiple reactions monitoring mode) operating in the positive mode...
March 23, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28334325/endocannabinoid-dependent-long-term-potentiation-of-synaptic-transmission-at-rat-barrel-cortex
#8
Laura Eva Maglio, José Antonio Noriega-Prieto, Maria Jesús Maraver, David Fernández de Sevilla
Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition...
March 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28327344/direct-activation-of-ca-2-and-voltage-gated-potassium-channels-of-large-conductance-by-anandamide-in-endothelial-cells-does-not-support-the-presence-of-endothelial-atypical-cannabinoid-receptor
#9
Alexander I Bondarenko, Olga Panasiuk, Iryna Okhai, Fabrizio Montecucco, Karim J Brandt, Francois Mach
Endocannabinoid anandamide induces endothelium-dependent relaxation commonly attributed to stimulation of the G-protein coupled endothelial anandamide receptor. The study addressed the receptor-independent effect of anandamide on large conductance Ca(2+)-dependent K(+) channels expressed in endothelial cell line EA.hy926. Under resting conditions, 10µM anandamide did not significantly influence the resting membrane potential. In a Ca(2+)-free solution the cells were depolarized by ~10mV. Further administration of 10µM anandamide hyperpolarized the cells by ~8mV...
March 19, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28325733/overactivation-of-the-endocannabinoid-system-alters-the-anti-lipolytic-action-of-insulin-in-mouse-adipose-tissue
#10
Tania Muller, Laurent Demizieux, Stéphanie Troy-Fioramonti, Joseph Gresti, Jean-Paul Pais de Barros, Hélène Berger, Bruno Vergès, Pascal Degrace
Evidence has accumulated that obesity-related metabolic dysregulation is associated with overactivation of the endocannabinoid system (ECS), which involves cannabinoid receptor 1 (CB1R), in peripheral tissues, including adipose tissue (AT). The functional consequences of CB1R activation on AT metabolism remain unclear. Since excess fat mobilization is considered an important primary event contributing to the onset of insulin resistance, we combined in vivo and in vitro experiments to investigate whether activation of ECS could alter the lipolytic rate...
March 21, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28301582/task-1-potassium-channel-is-not-critically-involved-in-mediating-hypoxic-pulmonary-vasoconstriction-of-murine-intra-pulmonary-arteries
#11
Ghulam Murtaza, Petra Mermer, Anna Goldenberg, Uwe Pfeil, Renate Paddenberg, Nobert Weissmann, Guenter Lochnit, Wolfgang Kummer
The two-pore domain potassium channel KCNK3 (TASK-1) is expressed in rat and human pulmonary artery smooth muscle cells. There, it is associated with hypoxia-induced signalling, and its dysfunction is linked to pathogenesis of human pulmonary hypertension. We here aimed to determine its role in hypoxic pulmonary vasoconstriction (HPV) in the mouse, and hence the suitability of this model for further mechanistic investigations, using appropriate inhibitors and TASK-1 knockout (KO) mice. RT-PCR revealed expression of TASK-1 mRNA in murine lungs and pre-acinar pulmonary arteries...
2017: PloS One
https://www.readbyqxmd.com/read/28293191/an-exploration-of-charge-compensating-ion-channels-across-the-phagocytic-vacuole-of-neutrophils
#12
Juliet R Foote, Philippe Behe, Mathew Frampton, Adam P Levine, Anthony W Segal
Neutrophils phagocytosing bacteria and fungi exhibit a burst of non-mitochondrial respiration that is required to kill and digest the engulfed microbes. This respiration is accomplished by the movement of electrons across the wall of the phagocytic vacuole by the neutrophil NADPH oxidase, NOX2. In this study, we have attempted to identify the non-proton ion channels or transporters involved in charge compensation by examining the effect of inhibitors on vacuolar pH and cross-sectional area, and on oxygen consumption...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28291580/restored-plasma-anandamide-and-endometrial-expression-of-fatty-acid-amide-hydrolase-in-women-with-polycystic-ovary-syndrome-by-the-combination-use-of-diane-35-and-metformin
#13
Na Cui, Xiaoye Feng, Zhiming Zhao, Jie Zhang, Yueming Xu, Luning Wang, Guimin Hao
PURPOSE: Polycystic ovary syndrome (PCOS) is a metabolic and endocrinal disorder affecting a number of women of reproductive age. We aimed to reveal the correlation between the endocannabinoid system and PCOS, which may provide a new therapeutic target for PCOS treatment. METHODS: Serum levels of anandamide and 2-arachidonoylglycerol andexpression of cannabinoid receptors and fatty acid amide hydrolase (FAAH) in the endometrium were compared between women with PCOS and infertile women without PCOS, as well as women with PCOS before and after treatment with Diane-35 and metformin...
March 10, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28284861/biological-evaluation-of-pyridone-alkaloids-on-the-endocannabinoid-system
#14
Andrea Chicca, Regina Berg, Henning J Jessen, Nicolas Marck, Fabian Schmid, Patrick Burch, Jürg Gertsch, Karl Gademann
Naturally occurring pyridone alkaloids as well as synthetic derivatives were previously shown to induce neurite outgrowth. However, the molecular basis for this biological effect remains poorly understood. In this work, we have prepared new pyridones, and tested the effect of thirteen 4-hydroxy-2-pyridone derivatives on the components of the endocannabinoid system. Investigation of binding affinities towards CB1 and CB2 receptors led to the identification of a compound binding selectively to CB1 (12). Compound 12 and a closely related derivative (11) also inhibited anandamide (AEA) hydrolysis by fatty acid amide hydrolase...
February 17, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28283967/exercise-training-and-high-fat-diet-elicit-endocannabinoid-system-modifications-in-the-rat-hypothalamus-and-hippocampus
#15
François-Xavier Gamelin, Julien Aucouturier, Fabio Arturo Iannotti, Fabiana Piscitelli, Enrico Mazzarella, Teresa Aveta, Melissa Leriche, Erwan Dupont, Caroline Cieniewski-Bernard, Erwan Leclair, Bruno Bastide, Vincenzo Di Marzo, Elsa Heyman
The purpose of the present study was to examine the effect of chronic exercise on the hypothalamus and hippocampus levels of the endocannabinoids (eCBs) anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and of two AEA congeners and on the expression of genes coding for CB1, CB2 receptors (Cnr1 and Cnr2, respectively), and the enzymes responsible for eCB biosynthesis and degradation, in rats fed with a standard or high-fat diet. Male Wistar rats (n = 28) were placed on a 12-week high-fat (HFD) or standard diet period, followed by 12 weeks of exercise training for half of each group...
March 10, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28261100/endocannabinoids-a-promising-impact-for-traumatic-brain-injury
#16
REVIEW
Lesley D Schurman, Aron H Lichtman
The endogenous cannabinoid (endocannabinoid) system regulates a diverse array of physiological processes and unsurprisingly possesses considerable potential targets for the potential treatment of numerous disease states, including two receptors (i.e., CB1 and CB2 receptors) and enzymes regulating their endogenous ligands N-arachidonoylethanolamine (anandamide) and 2-arachidonyl glycerol (2-AG). Increases in brain levels of endocannabinoids to pathogenic events suggest this system plays a role in compensatory repair mechanisms...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28247204/changes-in-the-brain-endocannabinoid-system-in-rat-models-of-depression
#17
Irena Smaga, Joanna Jastrzębska, Magdalena Zaniewska, Beata Bystrowska, Dawid Gawliński, Agata Faron-Górecka, Żaneta Broniowska, Joanna Miszkiel, Małgorzata Filip
A growing body of evidence implicates the endocannabinoid (eCB) system in the pathophysiology of depression. The aim of this study was to investigate the influence of changes in the eCB system, such as levels of neuromodulators, eCB synthesizing and degrading enzymes, and cannabinoid (CB) receptors, in different brain structures in animal models of depression using behavioral and biochemical analyses. Both models used, i.e., bulbectomized (OBX) and Wistar Kyoto (WKY) rats, were characterized at the behavioral level by increased immobility time...
April 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28240187/the-endocannabinoid-system-modulating-levels-of-consciousness-emotions-and-likely-dream-contents
#18
Eric Murillo-Rodriguez, José Carlos Pastrana-Trejo, Mireille Salas-Crisóstomo, Miriel de-la-Cruz
Cannabinoids are derivatives that are either compounds occurring naturally in the plant, Cannabis sativa or synthetic analogs of these molecules. The first and most widely investigated of the cannabinoids is ∆9-tetrahydrocannabinol (Δ9-THC), which is the main psychotropic constituent of cannabis and undergoes significant binding to cannabinoid receptors. These cannabinoid receptors are seven-transmembrane receptors that received their name from the fact that they respond to cannabinoid compounds, including Δ9-THC...
February 23, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28237711/pharmacological-inhibition-of-faah-modulates-tlr-induced-neuroinflammation-but-not-sickness-behaviour-an-effect-partially-mediated-by-central-trpv1
#19
Rebecca J Henry, Daniel M Kerr, Lisa E Flannery, Marykate Killilea, Edel M Hughes, Louise Corcoran, David P Finn, Michelle Roche
Aberrant activation of toll-like receptors (TLRs), key components of the innate immune system, has been proposed to underlie and exacerbate a range of central nervous system disorders. Increasing evidence supports a role for the endocannabinoid system in modulating inflammatory responses including those mediated by TLRs, and thus this system may provide an important treatment target for neuroinflammatory disorders. However, the effect of modulating endocannabinoid tone on TLR-induced neuroinflammation in vivo and associated behavioural changes is largely unknown...
February 22, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28220271/anandamide-oxidative-metabolism-induced-endoplasmic-reticulum-stress-and-apoptosis
#20
M Almada, B M Fonseca, C Amaral, M Diniz-da-Costa, G Correia-da-Silva, N Teixeira
The Endocannabinoid System (ECS) has been recognized as a crucial player in human reproduction. Changes in the levels of anandamide (AEA), the main endocannabinoid (eCB), negatively affect reproductive events, such as implantation, decidualization and placentation. Cyclooxygenase-2 (COX-2) is a major enzyme expressed in the endometrium and its involvement in female reproductive system has evolved over the last few years. Currently, COX-2 oxidative metabolism is emerging as a key mediator of AEA-induced actions...
February 20, 2017: Apoptosis: An International Journal on Programmed Cell Death
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