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https://www.readbyqxmd.com/read/29158048/enantiomer-specific-positive-allosteric-modulation-of-cb1-signaling-in-autaptic-hippocampal-neurons
#1
Jose Mitjavila, Danielle Yin, Pushkar M Kulkarni, Chiara Zanato, Ganesh A Thakur, Ruth Ross, Iain Greig, Ken Mackie, Alex Straiker
The cannabinoid signaling system is found throughout the CNS and its involvement in several pathological processes makes it an attractive therapeutic target. Because orthosteric CB1 cannabinoid receptor ligands have undesirable adverse effects there has been great interest in the development of allosteric modulators - both negative (NAMs) and positive (PAMs) - of these receptors. NAMs of CB1 appeared first on the scene, followed more recently by PAMs. Because allosteric modulation can vary depending on the orthosteric ligand it is important to study their function in a system that employs endogenous cannabinoids...
November 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29143869/peripheral-endocannabinoid-concentrations-are-not-associated-with-verbal-memory-impairment-during-mdma-intoxication
#2
E Haijen, M Farre, R de la Torre, A Pastor, E Olesti, N Pizarro, J G Ramaekers, K P C Kuypers
BACKGROUND: Preclinical data have suggested involvement of the endocannabinoid (eCB) system in MDMA-induced memory impairment. Clinical research has shown that blockade of the 5-HT2 receptor nulls memory impairment during MDMA intoxication. Interestingly, studies have demonstrated that the eCB and the 5-HT system interact. It was hypothesized that MDMA would cause an increase in eCB concentrations together with a decrease in memory performance, and that combining MDMA with a 5-HT2 receptor blocker ketanserin would lead to a counteraction of the MDMA effects on eCB concentrations and memory...
November 16, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29138268/n-acyl-amino-acids-elmiric-acids-endogenous-signaling-molecules-with-therapeutic-potential
#3
Sumner Burstein
The subject of N-acyl amino acid conjugates has been rapidly growing in recent years, especially with regard to their analgesic and anti-inflammatory actions. The field is comprised of a large family of lipid signaling molecules whose importance is only now being fully realized. The most widely studied member is N-arachidonoyl glycine (NAGly), which differs structurally from the endocannabinoid anandamide (N-arachidonoyl ethanolamide) by a single oxygen atom and the two are metabolically related. Topics that are covered in this mini review are: biosynthetic pathways for N-acyl amino acids, receptors for N-acyl amino acids, physiological actions of N-acyl amino acids, pharmacological effects of N-acyl amino acids and molecular mechanisms believed to be responsible for their effects...
November 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29138223/effect-of-maternal-high-fat-diet-on-key-components-of-the-placental-and-hepatic-endocannabinoid-system
#4
Kushal Gandhi, Cun Li, Nadezhda German, Cezary Skobowiat, Maira Carrillo, Raja Reddy Kallem, Eneko Larumbe, Stacy Martinez, Marcel Chuecos, Gary Ventolini, Peter Nathanielsz, Natalia Schlabritz-Loutsevitch
INTRODUCTION: Involvement of endogenous cannabinoids (eCBs) in obesity is well-characterized. However, information regarding eCB physiology in obesity associated with pregnancy is sparse. METHODS: From at least 9 months before conception, non-pregnant baboons (Papio spp.) were fed a diet of either 45% fat (HFD; n=11) or 12% fat or a control diet (CTR; n=11), and dietary intervention continued through pregnancy. Maternal and fetal venous plasma samples were evaluated using liquid chromatography-mass spectrometry to quantify anandamide (AEA) and 2-arachidonoyl glycerol (2-AG)...
November 14, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29131068/maternal-cannabinoid-use-alters-cannabinoid-cb1-and-endothelin-etb-receptor-expression-in-the-brains-of-dams-but-not-their-offspring
#5
Aarti Amlani, Mary G Hornick, Kevin Cooper, Preetha Prazad, Ramona Donovan, Anil Gulati
According to the 2015 National Survey on Drug Use and Health, cannabis (marijuana) is the most commonly used recreational drug in the US. Among pregnant women aged 14-55 years, 3.4% were cannabis users. Presently, little is known about the neurodevelopmental effect of cannabis use during pregnancy and/or nursing on neonates. Endothelin (ET) is essential for normal development of the central nervous system (CNS). Decreases in ETB receptor expression correlate with a decline in nerve growth factor (NGF) and an increase in vascular endothelial growth factor (VEGF) in postnatal brain...
November 4, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/29129206/differential-cytotoxicity-and-intracellular-calcium-signalling-following-activation-of-the-calcium-permeable-ion-channels-trpv1-and-trpa1
#6
Thomas Stueber, Mirjam J Eberhardt, Yaki Caspi, Shaya Lev, Alexander Binshtok, Andreas Leffler
Several members of the transient receptor channel (TRP) family can mediate a calcium-dependent cytotoxicity. In sensory neurons, vanilloids like capsaicin induce neurotoxicity by activating TRPV1. The closely related ion channel TRPA1 is also activated by irritants, but it is unclear if and how TRPA1 mediates cell death. In the present study we explored cytotoxicity and intracellular calcium signalling resulting from activation of TRPV1 and TRPA1, either heterologously expressed in HEK 293 cells or in native mouse dorsal root ganglion (DRG) neurons...
December 2017: Cell Calcium
https://www.readbyqxmd.com/read/29126855/n-docosahexaenoylethanolamine-synaptamide-carbon-14-radiolabeling-and-metabolic-studies
#7
Shilpa Sonti, Richard I Duclos, Mansi Tolia, Samuel J Gatley
N-Docosahexaenoylethanolamine (synaptamide) is structurally similar to the endocannabinoid N-arachidonoylethanolamine (anandamide), but incorporates the omega-3 22:6 fatty acid docosahexaenoic acid (DHA) in place of the omega-6 20:4 fatty acid arachidonic acid (AA). Some brain membrane lipid effects may be mediated via synaptamide. In competition experiments with mouse brain homogenate in vitro, we found that synaptamide was an order-of-magnitude poorer inhibitor of radioactive anandamide hydrolysis than was anandamide itself...
November 7, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/29118192/endocannabinoid-mediated-potentiation-of-non-nociceptive-synapses-contributes-to-behavioral-sensitization
#8
Yanqing Wang, Brian D Burrell
Endocannabinoids, such as 2-arachidonoyl glycerol (2-AG) and anandamide, can elicit long-term depression of both excitatory and inhibitory synapses. This latter effect will result in disinhibition and would therefore be expected to produce an increase in neural circuit output. However, there have been no examples directly linking endocannabinoid-mediated disinhibition to a change in a functional neurobehavioral circuit. The present study uses the well-characterized central nervous system (CNS) of the medicinal leech, Hirudo verbana, to examine the functional/behavioral relevance of endocannabinoid modulation of an identified afferent synapse...
November 8, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29110806/masturbation-to-orgasm-stimulates-the-release-of-the-endocannabinoid-2-arachidonoylglycerol-in-humans
#9
Johannes Fuss, Laura Bindila, Klaus Wiedemann, Matthias K Auer, Peer Briken, Sarah V Biedermann
BACKGROUND: Endocannabinoids are critical for rewarding behaviors such as eating, physical exercise, and social interaction. The role of endocannabinoids in mammalian sexual behavior has been suggested because of the influence of cannabinoid receptor agonists and antagonists on rodent sexual activity. However, the involvement of endocannabinoids in human sexual behavior has not been studied. AIM: To investigate plasma endocannabinoid levels before and after masturbation in healthy male and female volunteers...
November 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/29110674/characterization-of-endocannabinoids-and-related-acylethanolamides-in-the-synovial-fluid-of-dogs-with-osteoarthritis-a-pilot-study
#10
Carmela Valastro, Debora Campanile, Mariarosaria Marinaro, Delia Franchini, Fabiana Piscitelli, Roberta Verde, Vincenzo Di Marzo, Antonio Di Bello
BACKGROUND: Cannabis-based drugs have been shown to be effective in inflammatory diseases. A number of endocannabinoids including N- arachidonoylethanolamide (anandamide, AEA) and 2-arachidonyl glycerol (2-AG) with activity at the cannabinoid receptors (CBR) CBR1 and CBR2, have been identified. Other structurally related endogenous fatty acid compounds such as oleoylethanolamide (OEA) and palmitoyl ethanolamide (PEA) have been identified in biological tissues. These compounds do not bind to CBR but might be involved in facilitating the actions of directly acting endocannabinoids and thus are commonly termed "entourage" compounds due to their ability to modulate the endocannabinoid system...
November 6, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29108057/endocannabinoid-concentrations-in-plasma-during-the-finishing-period-are-associated-with-feed-efficiency-and-carcass-composition-of-beef-cattle
#11
V M Artegoitia, A P Foote, R G Tait, L A Kuehn, R M Lewis, T L Wheeler, H C Freetly
We previously have shown that plasma concentrations of endocannabinoids (EC) are positively correlated with feed efficiency and leaner carcasses in finishing steers. However, whether the animal growth during the finishing period affects the concentration of EC is unknown. The objective of this study was to quantify anandamide (AEA) and 2-arachidonyl glycerol (2-AG) in plasma during different stages of the finishing period and identify possible associations with production traits and carcass composition in beef calves...
October 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/29102876/maternal-high-fat-diet-induces-sex-specific-endocannabinoid-system-changes-in-newborn-rats-and-programs-adiposity-energy-expenditure-and-food-preference-in-adulthood
#12
Camilla P Dias-Rocha, Mariana M Almeida, Erika M Santana, Julia C B Costa, Juliana G Franco, Carmen C Pazos-Moura, Isis H Trevenzoli
Early life inadequate nutrition triggers developmental adaptations and adult chronic disease. Maternal high-fat (HF) diet promotes visceral obesity and hypothalamic leptin resistance in male rat offspring at weaning and adulthood. Obesity is related to over active endocannabinoid system (ECS). The ECS consists mainly of endogenous ligands, cannabinoid receptors (CB1 and CB2), and the enzymes fatty acid anandamide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). We hypothesized that perinatal maternal HF diet would regulate offspring ECS in hypothalamus and brown adipose tissue (BAT) at birth, prior to visceral obesity development, and program food preference and energy expenditure of adult offspring...
October 5, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29098188/translating-endocannabinoid-biology-into-clinical-practice-cannabidiol-for-stroke-prevention
#13
REVIEW
Eugene L Scharf
Introduction: The endocannabinoid system (ECS) regulates functions throughout human physiology, including neuropsychiatric, cardiovascular, autonomic, metabolic, and inflammatory states. The complex cellular interactions regulated by the ECS suggest a potential for vascular disease and stroke prevention by augmenting central nervous and immune cell endocannabinoid signaling. Discussion: The endocannabinoid N-arachidonoylethanolamine (anandamide) plays a central role in augmenting these processes in cerebrovascular and neurometabolic disease...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29097212/effects-of-acute-exposure-to-chlorpyrifos-on-cholinergic-and-non-cholinergic-targets-in-normal-and-high-fat-fed-male-c57bl-6j-mice
#14
Sandeep Kondakala, Jung Hwa Lee, Matthew K Ross, George E Howell
The prevalence of obesity is increasing at an alarming rate in the United States with 36.5% of adults being classified as obese. Compared to normal individuals, obese individuals have noted pathophysiological alterations which may alter the toxicokinetics of xenobiotics and therefore alter their toxicities. However, the effects of obesity on the toxicity of many widely utilized pesticides has not been established. Therefore, the present study was designed to determine if the obese phenotype altered the toxicity of the most widely used organophosphate (OP) insecticide, chlorpyrifos (CPS)...
December 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29071769/inhibition-of-fatty-acid-amide-hydrolase-in-the-central-amygdala-alleviates-co-morbid-expression-of-innate-anxiety-and-excessive-alcohol-intake
#15
Serena Stopponi, Yannick Fotio, Ana Domi, Anna Maria Borruto, Luis Natividad, Marisa Roberto, Roberto Ciccocioppo, Nazzareno Cannella
Fatty acid amide hydrolase (FAAH) is an enzyme that prominently degrades the major endocannabinoid N-arachidonoylethanolamine (anandamide). Inhibition of this enzyme leads to increased anandamide levels in brain regions that modulate stress and anxiety. Recently, we found that genetically selected Marchigian Sardinian alcohol-preferring (msP) rats display hyperactive FAAH in amygdalar regions that was associated with increased stress sensitivity and a hyper-anxious phenotype. Our previous work has also demonstrated that msPs display an innate preference for and excessive consumption of alcohol, potentially reflecting a form of self-medication to gain relief from hyper-anxious states...
October 26, 2017: Addiction Biology
https://www.readbyqxmd.com/read/29065362/pharmacological-augmentation-of-endocannabinoid-signaling-reduces-the-neuroendocrine-response-to-stress
#16
Pablo Nicolás Surkin, Sofia Ludmila Gallino, Valeria Luce, Fernando Correa, Javier Fernandez-Solari, Andrea De Laurentiis
Activation of the hypothalamic-pituitary-adrenal axis (HPA) is critical for survival when the organism is exposed to a stressful stimulus. The endocannabinoid system (ECS) is currently considered an important neuromodulator involved in numerous pathophysiological processes and whose primary function is to maintain homeostasis. In the tissues constituting the HPA axis, all the components of the ECS are present and the activation of this system acts in parallel with changes in the activity of numerous neurotransmitters, including nitric oxide (NO)...
October 18, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29059679/cannabinoids-regulate-the-diameter-of-pericyte-containing-retinal-capillaries-in-rats
#17
Yuan Zong, Xujiao Zhou, Jingyi Cheng, Jian Yu, Jihong Wu, Chunhui Jiang
BACKGROUND/AIMS: Cannabinoids are vasoactive substances that act as key regulators of arterial tone in the blood vessels supplying peripheral tissues and the central nervous system. We therefore investigated the effect of cannabinoids on retinal capillaries and pericytes. METHODS: The effects of cannabinoids on capillary diameters were determined using an ex vivo whole-mount rat retinal model. Western blotting, quantitative PCR, and immunohistochemistry were performed to explore the underlying mechanism...
October 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29046638/blockade-of-cannabinoid-cb1-receptors-in-the-dorsal-periaqueductal-gray-unmasks-the-antinociceptive-effect-of-local-injections-of-anandamide-in-mice
#18
Diego C Mascarenhas, Karina S Gomes, Tatiani Sorregotti, Ricardo L Nunes-de-Souza
Divergent results in pain management account for the growing number of studies aiming at elucidating the pharmacology of the endocannabinoid/endovanilloid anandamide (AEA) within several pain-related brain structures. For instance, the stimulation of both Transient Receptor Potential Vanilloid type 1 (TRPV1) and Cannabinoid type 1 (CB1) receptors led to paradoxical effects on nociception. Here, we attempted to propose a clear and reproducible methodology to achieve the antinociceptive effect of exogenous AEA within the dorsal periaqueductal gray (dPAG) of mice exposed to the tail-flick test...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29030083/human-bone-marrow-mesenchymal-stem-cells-secrete-endocannabinoids-that-stimulate-in-vitro-hematopoietic-stem-cell-migration-effectively-comparable-to-beta-adrenergic-stimulation
#19
Sevil Köse, Fatima Aerts-Kaya, Ağla Zübeyde Köprü, Emirhan Nemutlu, Barış Kuşkonmaz, Beren Karaosmanoğlu, Zihni Ekim Taşkıran, Belgin Altun, Duygu Uçkan Çetinkaya, Petek Korkusuz
Granulocyte Colony-Stimulating Factor (G-CSF) is a well-known hematopoietic stem cell (HSC) mobilizing agent used in both allogeneic and autologous transplantation. However, a proportion of patients or healthy donors fail to mobilize sufficient number of cells. New mobilization agents are therefore needed. Endocannabinoids (eCBs) are endogenous lipid mediators generated in the brain and peripheral tissues and activate the cannabinoid receptors (CB1, CB2). We suggest that eCBs may act as mobilizers of hematopoietic stem cells (HSC) from the BM under stress conditions as beta adrenergic receptors (Adrβ)...
October 10, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/29022083/adolescent-cannabinoid-exposure-effects-on-natural-reward-seeking-and-learning-in-rats
#20
H Schoch, M Y Huerta, C M Ruiz, M R Farrell, K M Jung, J J Huang, R R Campbell, D Piomelli, S V Mahler
RATIONALE: Adolescence is characterized by endocannabinoid (ECB)-dependent refinement of neural circuits underlying emotion, learning, and motivation. As a result, adolescent cannabinoid receptor stimulation (ACRS) with phytocannabinoids or synthetic agonists like "Spice" cause robust and persistent changes in both behavior and circuit architecture in rodents, including in reward-related regions like medial prefrontal cortex and nucleus accumbens (NAc). OBJECTIVES AND METHODS: Here, we examine persistent effects of ACRS with the cannabinoid receptor 1/2 specific agonist WIN55-212,2 (WIN; 1...
October 11, 2017: Psychopharmacology
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