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Anandamide

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https://www.readbyqxmd.com/read/28931663/targeting-fatty-acid-amide-hydrolase-as-a-therapeutic-strategy-for-antitussive-therapy
#1
Michael A Wortley, John J Adcock, Eric D Dubuis, Sarah A Maher, Sara J Bonvini, Isabelle Delescluse, Ross Kinloch, Gordon McMurray, Christelle Perros-Huguet, Marianthi Papakosta, Mark A Birrell, Maria G Belvisi
Cough is the most common reason to visit a primary care physician, yet it remains an unmet medical need. Fatty acid amide hydrolase (FAAH) is an enzyme that breaks down endocannabinoids, and inhibition of FAAH produces analgesic and anti-inflammatory effects. Cannabinoids inhibit vagal sensory nerve activation and the cough reflex, so it was hypothesised that FAAH inhibition would produce antitussive activity via elevation of endocannabinoids.Primary vagal ganglia neurons, tissue bioassay, in vivo electrophysiology and a conscious guinea pig cough model were utilised to investigate a role for fatty acid amides in modulating sensory nerve activation in vagal afferents...
September 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28912717/global-metabolomics-reveals-the-metabolic-dysfunction-in-ox-ldl-induced-macrophage-derived-foam-cells
#2
Wenjuan Xu, Ziyi Wei, Jiaojiao Dong, Feipeng Duan, Kuikui Chen, Chang Chen, Jie Liu, Xiaowei Yang, Lianming Chen, Hongbin Xiao, An Liu
Atherosclerosis (AS) is a chronic disorder of large arteries that is a major risk factors of high morbidity and mortality. Oxidative modification LDL is one of the important contributors to atherogenesis. Macrophages take up ox-LDL and convert into foam cells, which is the hallmark of AS. To advance the understanding of the metabolic perturbation involved in ox-LDL induced macrophage-derived foam cells and discover the potential biomarkers of early AS, a global metabolomics approach was applied based on UHPLC-QTOF/MS...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28910408/effects-of-tumour-necrosis-factor-%C3%AE-upon-the-metabolism-of-the-endocannabinoid-anandamide-in-prostate-cancer-cells
#3
Jessica Karlsson, Sandra Gouveia-Figueira, Mireille Alhouayek, Christopher J Fowler
Tumour necrosis factor α (TNFα) is involved in the pathogenesis of prostate cancer, a disease where disturbances in the endocannabinoid system are seen. In the present study we have investigated whether treatment of DU145 human prostate cancer cells affects anandamide (AEA) catabolic pathways. Additionally, we have investigated whether cyclooxygenase-2 (COX-2) can regulate the uptake of AEA into cells. Levels of AEA synthetic and catabolic enzymes were determined by qPCR. AEA uptake and hydrolysis in DU145 and RAW264...
2017: PloS One
https://www.readbyqxmd.com/read/28899508/pellitorine-an-extract-of-tetradium-daniellii-is-an-antagonist-of-the-ion-channel-trpv1
#4
Zoltán Oláh, Dóra Rédei, László Pecze, Csaba Vizler, Katalin Jósvay, Péter Forgó, Zoltán Winter, György Dombi, Gerda Szakonyi, Judit Hohmann
BACKGROUND: Transient Receptor Potential Vanilloid 1 (TRPV1) confers noxious heat and inflammatory pain signals in the peripheral nervous system. Clinical trial of resiniferatoxin from Euphorbia species is successfully aimed at TRPV1 in cancer pain management and heading toward new selective painkiller status that further validates this target for drug discovery efforts. Evodia species, used in traditional medicine for hundreds of years, are a recognised source of different TRPV1 agonists, but no antagonist has yet been reported...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28890367/enhanced-anandamide-signaling-reduces-flight-behavior-elicited-by-an-approaching-robo-beetle
#5
Daniel E Heinz, Andreas Genewsky, Carsten T Wotjak
Our current knowledge of the implications of endocannabinoids in fear and anxiety is largely based on fear conditioning paradigms and approach-avoidance conflicts. Here we establish the ethobehavioral beetle mania task (BMT), which confronts mice with an erratically moving robo-beetle. With the help of this task we demonstrate decreased tolerance yet increased avoidance responses to an approaching beetle in high-anxiety behavior (HAB) and BALBc mice compared to C57BL/6N, CD1 and normal-anxiety behavior (NAB) mice...
September 7, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28889355/tingenone-a-pentacyclic-triterpene-induces-peripheral-antinociception-due-to-cannabinoid-receptors-activation-in-mice
#6
C C Veloso, R C M Ferreira, V G Rodrigues, L P Duarte, A Klein, I D Duarte, T R L Romero, A C Perez
Several works have shown that triterpenes induce peripheral antinociception by activation of cannabinoid receptors and endocannabinoids; besides, several research groups have reported activation of cannabinoid receptors in peripheral antinociception. The aim of this study was to assess the involvement of the cannabinoid system in the antinociceptive effect induced by tingenone against hyperalgesia evoked by prostaglandin E2 (PGE2) at peripheral level. The paw pressure test was used and the hyperalgesia was induced by intraplantar injection of PGE2 (2 μg/paw)...
September 9, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28875399/interplay-between-n-3-and-n-6-long-chain-polyunsaturated-fatty-acids-and-the-endocannabinoid-system-in-brain-protection-and-repair
#7
REVIEW
Simon C Dyall
The brain is enriched in arachidonic acid (ARA) and docosahexaenoic acid (DHA), long-chain polyunsaturated fatty acids (LCPUFAs) of the n-6 and n-3 series, respectively. Both are essential for optimal brain development and function. Dietary enrichment with DHA and other long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA), has shown beneficial effects on learning and memory, neuroinflammatory processes, and synaptic plasticity and neurogenesis. ARA, DHA and EPA are precursors to a diverse repertoire of bioactive lipid mediators, including endocannabinoids...
September 5, 2017: Lipids
https://www.readbyqxmd.com/read/28869110/anandamide-exerts-a-suppressive-effect-on-sperm-binding-to-oviduct-explants-through-cb1-receptors-in-the-water-buffalo-bubalus-bubalis
#8
Vimlesh Kumar, Arumugam Kumaresan, Puneeth Kumar D S, Sreela Lathika, Samiksha Nayak, Kaustubh Kishor Saraf, Pradeep Nag B S, Shivani Chhillar, Tirtha Kumar Datta, Tushar Kumar Mohanty
An endocannabinoid system comprising of Anandamide (AEA) and its receptor has been shown to play a role in sperm acquisition of fertilizing potential and sperm-oviduct interaction. In the present study, we assessed the effect of sperm pre-treatment with AEA or co-incubation of sperm-oviduct explants with AEA in the presence or absence of CB1 receptor antagonist (SR141716A) on sperm-oviduct binding in the water buffalo. Cryopreserved spermatozoa from 3 Murrah buffalo bulls (3 ejaculates from each bull) were utilized for the study...
October 2017: Animal Reproduction Science
https://www.readbyqxmd.com/read/28843504/mammalian-enzymes-responsible-for-the-biosynthesis-of-n-acylethanolamines
#9
REVIEW
Zahir Hussain, Toru Uyama, Kazuhito Tsuboi, Natsuo Ueda
Bioactive N-acylethanolamines (NAEs) are ethanolamides of long-chain fatty acids, including palmitoylethanolamide, oleoylethanolamide and anandamide. In animal tissues, NAEs are biosynthesized from membrane phospholipids. The classical "transacylation-phosphodiesterase" pathway proceeds via N-acyl-phosphatidylethanolamine (NAPE), which involves the actions of two enzymes, NAPE-generating Ca(2+)-dependent N-acyltransferase (Ca-NAT) and NAPE-hydrolyzing phospholipase D (NAPE-PLD). Recent identification of Ca-NAT as Ɛ isoform of cytosolic phospholipase A2 enabled the further molecular biological approaches toward this enzyme...
August 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28826718/contrasting-effects-of-selective-magl-and-faah-inhibition-on-dopamine-depletion-and-gdnf-expression-in-a-chronic-mptp-mouse-model-of-parkinson-s-disease
#10
Noemi Pasquarelli, Christoph Porazik, Hanna Bayer, Eva Buck, Stefan Schildknecht, Patrick Weydt, Anke Witting, Boris Ferger
The modulation of the brain endocannabinoid system has been identified as an option to treat neurodegenerative diseases including Parkinson's disease (PD). Especially the elevation of endocannabinoid levels by inhibition of hydrolytic degradation represents a valuable approach. To evaluate whether monoacylglycerol lipase (MAGL) or fatty acid amide hydrolase (FAAH) inhibition could be beneficial for PD, we examined in parallel the therapeutic potential of the highly selective MAGL inhibitor KML29 elevating 2-arachidonoylglyerol (2-AG) levels and the highly selective FAAH inhibitor PF-3845 elevating anandamide (AEA) levels in a chronic methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/probenecid) mouse model of PD...
August 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28826539/endocannabinoid-turnover
#11
Christopher J Fowler, Patrick Doherty, Stephen P H Alexander
In this review, we consider the biosynthetic, hydrolytic, and oxidative metabolism of the endocannabinoids anandamide and 2-arachidonoylglycerol. We describe the enzymes associated with these events and their characterization. We identify the inhibitor profile for these enzymes and the status of therapeutic exploitation, which to date has been limited to clinical trials for fatty acid amide hydrolase inhibitors. To bring the review to a close, we consider whether point block of a single enzyme is likely to be the most successful approach for therapeutic exploitation of the endocannabinoid system...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28826537/actions-and-regulation-of-ionotropic-cannabinoid-receptors
#12
Luciano De Petrocellis, Massimo Nabissi, Giorgio Santoni, Alessia Ligresti
Almost three decades have passed since the identification of the two specific metabotropic receptors mediating cannabinoid pharmacology. Thereafter, many cannabinoid effects, both at central and peripheral levels, have been well documented and characterized. However, numerous evidences demonstrated that these pharmacological actions could not be attributable solely to the activation of CB1 and CB2 receptors since several important cannabimimetic actions have been found in biological systems lacking CB1 or CB2 gene such as in specific cell lines or transgenic mice...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28826535/functional-selectivity-at-cannabinoid-receptors
#13
Richard Priestley, Michelle Glass, David Kendall
It is now clear that, in contrast to traditional descriptions of G protein-coupled receptor signaling, agonists can activate or inhibit characteristic patterns of downstream effector pathways depending on their structures and the conformational changes induced in the receptor. This is referred to as functional selectivity (also known as agonist-directed trafficking, ligand-induced differential signaling, or biased agonism). It is important because even small structural differences can result in significant variations in overall agonist effects (wanted and unwanted) depending on which postreceptor signaling systems are engaged by each agonist/receptor pairing...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28826534/cb1-and-cb2-receptor-pharmacology
#14
Allyn C Howlett, Mary E Abood
The CB1 and CB2 cannabinoid receptors (CB1R, CB2R) are members of the G protein-coupled receptor (GPCR) family that were identified over 20 years ago. CB1Rs and CB2Rs mediate the effects of Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the principal psychoactive constituent of marijuana, and subsequently identified endogenous cannabinoids (endocannabinoids) anandamide and 2-arachidonoyl glycerol. CB1Rs and CB2Rs have both similarities and differences in their pharmacology. Both receptors recognize multiple classes of agonist and antagonist compounds and produce an array of distinct downstream effects...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28826532/endocannabinoid-analytical-methodologies-techniques-that-drive-discoveries-that-drive-techniques
#15
Fabiana Piscitelli, Heather B Bradshaw
Identification of the two major endogenous cannabinoid ligands, known as endocannabinoids, N-arachidonoyl-ethanolamine (anandamide, AEA) and 2-arachidonoyl-glycerol (2-AG), opened the way for the identification and isolation of other lipid congeners, all derivatives of fatty acids and related to the Endocannabinoid System. The nomenclature of this anandamide-type class of lipids is evolving as new species are discovered all the time. However, they each fall under the larger umbrella of lipids that are a conjugation of a fatty acid with an amine through and amide bond, which we will refer to as lipoamines...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28820005/inhibition-of-endocannabinoid-metabolizing-enzymes-in-peripheral-tissues-following-developmental-chlorpyrifos-exposure-in-rats
#16
Robert W Buntyn, Navatha Alugubelly, Rachel L Hybart, Afzaal N Mohammed, Carole A Nail, Greta C Parker, Matthew K Ross, Russell L Carr
Repeated developmental exposure to the organophosphate (OP) insecticide chlorpyrifos (CPF) inhibits brain fatty acid amide hydrolase (FAAH) activity at low levels, whereas at higher levels, it inhibits brain monoacylglycerol lipase (MAGL) activity. FAAH and MAGL hydrolyze the endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG), respectively. Peripherally, AEA and 2-AG have physiological roles in the regulation of lipid metabolism and immune function, and altering the normal levels of these lipid mediators can negatively affect these processes...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/28814985/activation-of-endocannabinoid-receptor-2-as-a-mechanism-of-propofol-pretreatment-induced-cardioprotection-against-ischemia-reperfusion-injury-in-rats
#17
Hai-Jing Sun, Yan Lu, Hao-Wei Wang, Hao Zhang, Shuang-Ran Wang, Wen-Yun Xu, Hai-Long Fu, Xue-Ya Yao, Feng Yang, Hong-Bin Yuan
Propofol pretreatment before reperfusion, or propofol conditioning, has been shown to be cardioprotective, while its mechanism is unclear. The current study investigated the roles of endocannabinoid signaling in propofol cardioprotection in an in vivo model of myocardial ischemia/reperfusion (I/R) injury and in in vitro primary cardiomyocyte hypoxia/reoxygenation (H/R) injury. The results showed that propofol conditioning increased both serum and cell culture media concentrations of endocannabinoids including anandamide (AEA) and 2-arachidonoylglycerol (2-AG) detected by LC-MS/MS...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28810692/resveratrol-protects-from-lipopolysaccharide-induced-inflammation-in-the-uterus-and-prevents-experimental-preterm-birth
#18
María Victoria Bariani, Fernando Correa, Emma Leishman, Ana Paula Domínguez Rubio, Andreína Arias, Aníbal Stern, Heather B Bradshaw, Ana María Franchi
STUDY QUESTION: Is resveratrol able to prevent the lipopolysaccharide (LPS)-induced preterm labor in 15-day pregnant BALB/c mice? SUMMARY ANSWER: Resveratrol prevented the LPS-induced onset of preterm labor in 64% of the cases and showed anti-inflammatory and tocolytic effects by downregulating COX-2 and iNOS expression and NOS activity, and by changing the uterine prostaglandin and endocannabinoid profiling. WHAT IS KNOWN ALREADY: Genital tract infections by Gram-negative bacteria are a common complication in human pregnancy and have been shown to increase risk of preterm delivery...
August 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28808587/oral-administration-of-the-endocannabinoid-anandamide-during-lactation-effects-on-hypothalamic-cannabinoid-type-1-receptor-and-food-intake-in-adult-mice
#19
Carolina Aguirre, Valeska Castillo, Miguel Llanos
We have previously shown that administration of the endocannabinoid anandamide (AEA) during lactation leads to overweight, increased body fat accumulation, and insulin resistance in adult mice. This study was designed to elucidate if these effects are due to increased food intake, stimulated by an augmented abundance and binding ability of the hypothalamic cannabinoid type 1 receptor (CB1R). With this aim, male mice pups were treated with a daily oral dose of AEA during lactation. Adult mice were also treated with a single oral dose of AEA, to evaluate acute food intake during 4 h...
2017: Journal of Nutrition and Metabolism
https://www.readbyqxmd.com/read/28805944/suppression-of-acute-and-anticipatory-nausea-by-peripherally-restricted-faah-inhibitor-in-animal-models-role-of-ppar%C3%AE-and-cb1-receptors
#20
Erin M Rock, Guillermo Moreno-Sanz, Cheryl L Limebeer, Gavin N Petrie, Roberto Angelini, Daniele Piomelli, Linda A Parker
To evaluate the ability of the peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor, URB937 (cyclohexylcarbamic acid 3'-carbamoyl-6-hydroxybiphenyl-3-yl ester) to suppress acute and anticipatory nausea in rats, and to examine the pharmacological mechanism of such an effect. EXPERIMENTAL APPROACH: We investigated the potential of URB937 to reduce the establishment of lithium chloride (LiCl)-induced conditioned gaping (a model of acute nausea) and to reduce the expression of contextually elicited conditioned gaping (a model of anticipatory nausea) in rats...
August 14, 2017: British Journal of Pharmacology
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