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https://www.readbyqxmd.com/read/29130941/remote-ischemia-preconditioning-attenuates-blood-spinal-cord-barrier-breakdown-in-rats-undergoing-spinal-cord-ischemia-reperfusion-injury-associated-with-activation-and-upregulation-of-cb1-and-cb2-receptors
#1
Na Jing, Bo Fang, Zhi-Lin Wang, Hong Ma
BACKGROUND/AIMS: Remote ischemic preconditioning (RIPC) has protective effects on spinal cord ischemia reperfusion (I/R) injury, but the potential mechanisms remain unclear. In our study, the effects and underlying mechanisms of RIPC on blood-spinal cord barrier (BSCB) breakdown following I/R injury were investigated. METHODS: animals underwent intraperitoneal administration with cannabinoid-1 (CB1) receptor antagonist AM251, cannabinoid-2 (CB2) receptor antagonist AM630 or vehicle 15 minutes before three 3-minute occlusion-reperfusion cycles on the right femoral artery or a sham operation...
October 31, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29128791/acpa-and-jwh-133-modulate-the-vascular-tone-of-superior-mesenteric-arteries-through-cannabinoid-receptors-bkca-channels-and-nitric-oxide-dependent-mechanisms
#2
Evelyn López-Dyck, Felipa Andrade-Urzúa, Alejandro Elizalde, Tania Ferrer-Villada, Adan Dagnino-Acosta, Miguel Huerta, Zyanya Osuna-Calleros, Cinthia Rangel-Sandoval, Enrique Sánchez-Pastor
BACKGROUND: Some cannabinoids, a family of compounds derived from Cannabis sativa (marijuana), have previously shown vasodilator effects in several studies, a feature that makes them suitable for the generation of a potential treatment for hypertension. The mechanism underlying this vasodilator effect in arteries is still controversial. In this report, we explored how the synthetic cannabinoids ACPA (CB1-selective agonist) and JWH-133 (CB2-selective agonist) regulate the vascular tone of rat superior mesenteric arteries...
July 1, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29127599/cb1-receptors-mediated-inhibition-of-atp-induced-ca-2-i-increase-in-cultured-rat-spinal-dorsal-horn-neurons
#3
Jingdong Long, Xiaolu Lei, Meiyun Chen, Shulei Yang, Tao Sun, Junwei Zeng, Deqian Yu, Hong Tian, Xiaohong Liu
Spinal cannabinoid receptor 1 (CB1R) and purinergic P2X receptors (P2XR) play a critical role in the process of pathological pain. Both CB1R and P2XR are expressed in spinal dorsal horn (DH) neurons. It is not clear whether CB1 receptor activation modulates the function of P2X receptor channels within dorsal horn. For this reason, we observed the effect of CP55940 (cannabinoid receptor agonist) on ATP-induced Ca(2+) mobilization in cultured rat DH neurons. The changes of intracellular calcium concentration ([Ca(2+)]i) were detected with confocal laser scanning microscopy using fluo-4/AM as a calcium fluorescent indicator...
November 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29126730/optimization-of-pharmacokinetic-properties-by-modification-of-a-carbazole-based-cannabinoid-receptor-subtype-2-cb2-ligand
#4
Dominik Heimann, Frederik Börgel, Henk de Vries, Kim Bachmann, Victoria E Rose, Bastian Frehland, Dirk Schepmann, Laura H Heitman, Bernhard Wünsch
Recently, the development of the fluorinated PET tracer [(18)F]1a for imaging of CB2 receptors in the central nervous system was reported. [(18)F]1a showed high CB2 affinity and selectivity over the CB1 subtype, but rapid biotransformation in mice. In addition to the amide hydrolysis, oxidative N-dealkylation and carbazole oxidation were postulated as main metabolic pathways. Based on these results, novel carbazole derivatives with additional 6-substituents (23a, 24a), modified hydrogenation state (26a) and enlarged fluoroalkyl substituent (13a, 13b) were synthesized and pharmacologically evaluated...
October 16, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29120578/role-of-cannabinoid-cb2-receptor-gene-cnr2-polymorphism-in-children-with-immune-thrombocytopenic-purpura-in-beni-suef-governorate-in-egypt
#5
Dina A Ezzat, Amira A Hammam, Waleed M El-Malah, Rasha A Khattab, Eman M Mangoud
The cannabinoid system is involved in the immune regulation by modulation of Th cells type 1 and 2. It is composed of the CB2 receptor which is expressed at 10 to 100 folds greater levels on immune cells than the CB1 receptors. The CB2 is encoded by the cannabinoid CB receptor gene (CNR2) gene. This study aims to investigate the polymorphism in CNR2 gene variation rs 35761398 (Q63R) in Egyptian children with immune thrombocytopenic purpura and to investigate the relation between this gene polymorphism and either the susceptibility to or the chronicity of the disease...
January 2017: Egyptian Journal of Immunology
https://www.readbyqxmd.com/read/29113898/finding-order-in-chemical-chaos-continuing-characterization-of-synthetic-cannabinoid-receptor-agonists
#6
REVIEW
Julie A Marusich, Jenny L Wiley, Timothy W Lefever, Purvi R Patel, Brian F Thomas
Diversion of synthetic cannabinoids from the lab to drugs of abuse has become increasingly prevalent in recent years. Moreover, as earlier synthetic cannabinoids were banned, manufacturers introduced a new supply of novel compounds to serve as replacements. Hence, the chemical diversity of synthetic cannabinoid analogs has also rapidly increased. The present study examined 8 new synthetic cannabinoids: AM-1220, AM-2232, AM-2233, AM-679, EAM-2201, JWH-210, JHW-251, and MAM-2201. Each compound was assessed for binding affinity and functional activation of CB1 and CB2 receptors, and pharmacological equivalence with Δ(9)-tetrahydrocannabinol (THC) in THC drug discrimination...
November 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29111112/anti-migraine-effect-of-%C3%A2-9-tetrahydrocannabinol-in-the-female-rat
#7
Ram Kandasamy, Cole T Dawson, Rebecca M Craft, Michael M Morgan
Current anti-migraine treatments have limited efficacy and many side effects. Although anecdotal evidence suggests that marijuana is useful for migraine, this hypothesis has not been tested in a controlled experiment. Thus, the present study tested whether administration of ∆(9)-tetrahydrocannabinol (THC) produces anti-migraine effects in the female rat. Microinjection of the TRPA1 agonist allyl isothiocyanate (AITC) onto the dura mater produced migraine-like pain for 3h as measured by depression of home cage wheel running...
October 28, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29110748/perinatal-maternal-high-fat-diet-induces-early-obesity-and-sex-specific-alterations-of-the-endocannabinoid-system-in-white-and-brown-adipose-tissue-of-weanling-rat-offspring
#8
Mariana M Almeida, Camilla P Dias-Rocha, André S Souza, Mariana F Muros, Leonardo S Mendonca, Carmen C Pazos-Moura, Isis H Trevenzoli
Perinatal maternal high-fat (HF) diet programmes offspring obesity. Obesity is associated with overactivation of the endocannabinoid system (ECS) in adult subjects, but the role of the ECS in the developmental origins of obesity is mostly unknown. The ECS consists of endocannabinoids, cannabinoid receptors (cannabinoid type-1 receptor (CB1) and cannabinoid type-2 receptor (CB2)) and metabolising enzymes. We hypothesised that perinatal maternal HF diet would alter the ECS in a sex-dependent manner in white and brown adipose tissue of rat offspring at weaning in parallel to obesity development...
November 7, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/29110331/radioligands-for-positron-emission-tomography-imaging-of-cannabinoid-type-2-receptor
#9
Francesco Spinelli, Linjing Mu, Simon M Ametamey
The cannabinoid type 2 (CB2) receptor is an immunomodulatory receptor mainly expressed in peripheral cells and organs of the immune system. The expression level of CB2 in the central nervous system under physiological conditions is negligible, however under neuroinflammatory conditions an upregulation of CB2 protein or mRNA mainly co-localized with activated microglial cells has been reported. Consequently, CB2 agonists have been confirmed to play a role in neuroprotective and anti-inflammatory processes. A suitable PET radioligand for imaging CB2 would provide an invaluable research tool to explore the role of CB2 receptor expression in inflammatory disorders...
November 6, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29109685/binding-and-signaling-studies-disclose-a-potential-allosteric-site-for-cannabidiol-in-cannabinoid-cb2-receptors
#10
Eva Martínez-Pinilla, Katia Varani, Irene Reyes-Resina, Edgar Angelats, Fabrizio Vincenzi, Carlos Ferreiro-Vera, Julen Oyarzabal, Enric I Canela, José L Lanciego, Xavier Nadal, Gemma Navarro, Pier Andrea Borea, Rafael Franco
The mechanism of action of cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa L., is not completely understood. First assumed that the compound was acting via cannabinoid CB2 receptors (CB2Rs) it is now suggested that it interacts with non-cannabinoid G-protein-coupled receptors (GPCRs); however, CBD does not bind with high affinity to the orthosteric site of any GPCR. To search for alternative explanations, we tested CBD as a potential allosteric ligand of CB2R. Radioligand and non-radioactive homogeneous binding, intracellular cAMP determination and ERK1/2 phosphorylation assays were undertaken in heterologous systems expressing the human version of CB2R...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29108864/neuro-glial-cannabinoid-receptors-modulate-signaling-in-the-embryonic-avian-retina
#11
Regina C C Kubrusly, Alexander Günter, Luzia Sampaio, Roberta Silva Martins, Clarissa S Schitine, Priscila Trindade, Arlete Fernandes, Rosa Borelli-Torres, Vivian Sayuri Miya-Coreixas, Anna Carolina Rego Costa, Hércules Rezende Freitas, Patrícia F Gardino, Fernando G de Mello, Karin Costa Calaza, Ricardo A M Reis
Endocannabinoids are endogenous lipids that activate selective G protein coupled receptors (CB1 and CB2), mostly found at neuronal presynaptic sites in the nervous system. One of the main consequences of the activation of CB receptors is a decrease in GABA or glutamate release, controlling cell excitability. Here we studied the expression of CB1 and CB2 receptors in E8C8 cultured retina cells (embryonic day 8 and 8 days in vitro) using immunocytochemistry and western blot analysis. We also evaluated their functions in terms of cyclic AMP (cAMP) production, single cell calcium imaging (SCCI) and GABA release induced in basal conditions or activated by l-Aspartate (L-ASP) in cell cultures or under ischemia in young chick retina...
November 3, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/29105060/cannabinoid-receptor-1-2-double-knockout-mice-develop-epilepsy
#12
Shane Rowley, Xiaofei Sun, Isabel V Lima, Alexandra Tavenier, Antonio Carlos Pinheiro de Oliveira, Sudhansu K Dey, Steve C Danzer
The endocannabinoid system has gained attention as an important modulator of activity in the central nervous system. Initial studies focused on cannabinoid receptor 1 (CB1), which is widely expressed in the brain, but recent work also implicates cannabinoid receptor 2 (CB2) in modulating neuronal activity. Both receptors are capable of reducing neuronal activity, generating interest in cannabinoid receptor agonists as potential anticonvulsants. CB1 (Cnr1) and CB2 (Cnr2) single-knockout mice have been generated, with the former showing heightened seizure sensitivity, but not overt seizures...
November 3, 2017: Epilepsia
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
#13
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/29098189/an-update-on-non-cb1-non-cb2-cannabinoid-related-g-protein-coupled-receptors
#14
REVIEW
Paula Morales, Patricia H Reggio
The endocannabinoid system (ECS) has been shown to be of great importance in the regulation of numerous physiological and pathological processes. To date, two Class A G-protein-coupled receptors (GPCRs) have been discovered and validated as the main therapeutic targets of this system: the cannabinoid receptor type 1 (CB1), which is the most abundant neuromodulatory receptor in the brain, and the cannabinoid receptor type 2 (CB2), predominantly found in the immune system among other organs and tissues. Endogenous cannabinoid receptor ligands (endocannabinoids) and the enzymes involved in their synthesis, cell uptake, and degradation have also been identified as part of the ECS...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29098187/review-the-role-of-cannabinoids-on-esophageal-function-what-we-know-thus-far
#15
REVIEW
Jonathan Gotfried, Rahul Kataria, Ron Schey
The endocannabinoid system (ECS) primarily consists of cannabinoid receptors (CBRs), endogenous ligands, and enzymes for endocannabinoid biosynthesis and inactivation. Although the presence of CBRs, both CB1 and CB2, as well as a third receptor (G-protein receptor 55 [GPR55]), has been established in the gastrointestinal (GI) tract, few studies have focused on the role of cannabinoids on esophageal function. To date, studies have shown their effect on GI motility, inflammation and immunity, intestinal and gastric acid secretion, nociception and emesis pathways, and appetite control...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29083450/the-potential-of-cannabidiol-treatment-for-cannabis-users-with-recent-onset-psychosis
#16
Britta Hahn
A major factor associated with poor prognostic outcome after a first psychotic break is cannabis misuse, which is prevalent in schizophrenia and particularly common in individuals with recent-onset psychosis. Behavioral interventions aimed at reducing cannabis use have been unsuccessful in this population. Cannabidiol (CBD) is a phytocannabinoid found in cannabis, although at low concentrations in modern-day strains. CBD has a broad pharmacological profile, but contrary to ∆9-tetrahydrocannabinol (THC), CBD does not activate CB1 or CB2 receptors and has at most subtle subjective effects...
August 11, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/29082314/anti-inflammatory-activity-in-colon-models-is-derived-from-%C3%AE-9-tetrahydrocannabinolic-acid-that-interacts-with-additional-compounds-in-cannabis-extracts
#17
Rameshprabu Nallathambi, Moran Mazuz, Aurel Ion, Gopinath Selvaraj, Smadar Weininger, Marcelo Fridlender, Ahmad Nasser, Oded Sagee, Puja Kumari, Diana Nemichenizer, Maayan Mendelovitz, Nave Firstein, Orly Hanin, Fred Konikoff, Yoram Kapulnik, Timna Naftali, Hinanit Koltai
Introduction: Inflammatory bowel diseases (IBDs) include Crohn's disease, and ulcerative colitis. Cannabis sativa preparations have beneficial effects for IBD patients. However, C. sativa extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of whole C. sativa extracts has never been characterized in detail with in vitro and ex vivo colon models. Material and Methods: The anti-inflammatory activity of C...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29069083/rhogef9-splice-isoforms-influence-neuronal-maturation-and-synapse-formation-downstream-of-%C3%AE-2-gabaa-receptors
#18
Claire de Groot, Amalia Floriou-Servou, Yuan-Chen Tsai, Simon Früh, Manuela Kohler, Georgia Parkin, Cornelia Schwerdel, Giovanna Bosshard, Kai Kaila, Jean-Marc Fritschy, Shiva K Tyagarajan
In developing brain neuronal migration, dendrite outgrowth and dendritic spine outgrowth are controlled by Cdc42, a small GTPase of the Rho family, and its activators. Cdc42 function in promoting actin polymerization is crucial for glutamatergic synapse regulation. Here, we focus on GABAergic synapse-specific activator of Cdc42, collybistin (CB) and examine functional differences between its splice isoforms CB1 and CB2. We report that CB1 and CB2 differentially regulate GABAergic synapse formation in vitro along proximal-distal axis and adult-born neuron maturation in vivo...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29066974/cannabinoids-modulate-neuronal-activity-and-cancer-by-cb1-and-cb2-receptor-independent-mechanisms
#19
REVIEW
Ken Soderstrom, Eman Soliman, Rukiyah Van Dross
Cannabinoids include the active constituents of Cannabis or are molecules that mimic the structure and/or function of these Cannabis-derived molecules. Cannabinoids produce many of their cellular and organ system effects by interacting with the well-characterized CB1 and CB2 receptors. However, it has become clear that not all effects of cannabinoid drugs are attributable to their interaction with CB1 and CB2 receptors. Evidence now demonstrates that cannabinoid agents produce effects by modulating activity of the entire array of cellular macromolecules targeted by other drug classes, including: other receptor types; ion channels; transporters; enzymes, and protein- and non-protein cellular structures...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29065362/pharmacological-augmentation-of-endocannabinoid-signaling-reduces-the-neuroendocrine-response-to-stress
#20
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
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