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https://www.readbyqxmd.com/read/28934522/effects-of-cannabinoid-agonists-and-antagonists-on-sleep-and-breathing-in-sprague-dawley-rats
#1
Michael W Calik, David W Carley
Study Objectives: There are no pharmacological treatments for obstructive sleep apnea syndrome, but dronabinol showed promise in a small pilot study. In anesthetized rats, dronabinol attenuates reflex apnea via activation of cannabinoid (CB) receptors located on vagal afferents; an effect blocked by cannabinoid type 1 (CB1) and/or type 2 (CB2) receptor antagonists. Here, using a natural model of central sleep apnea, we examine the effects of dronabinol, alone and in combination with selective antagonists in conscious rats chronically instrumented to stage sleep and measure cessation of breathing...
September 1, 2017: Sleep
https://www.readbyqxmd.com/read/28931663/targeting-fatty-acid-amide-hydrolase-as-a-therapeutic-strategy-for-antitussive-therapy
#2
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/28917977/the-role-of-the-endocannabinoid-system-in-the-antihyperalgesic-effect-of-cedrus-atlantica-essential-oil-inhalation-in-a-mouse-model-of-postoperative-pain
#3
Aline Armiliato Emer, Nathalia Nahas Donatello, Ana Paula Batisti, Luiz Augusto Oliveira Belmonte, Adair R S Santos, Daniel F Martins
ETHNOPHARMACOLOGICAL RELEVANCE: Cedar is part of the phylum of conifers, and it's essential oil has been used for therapeutic purposes since ancient times. In our previous study, we have demonstrated that the inhalation of the Cedrus atlantica essential oil (CaEO) induces an antihyperalgesic effect in a model of postoperative pain. But the mechanism that underlies this effect is not yet fully known. AIM OF THE STUDY: This study investigates the involvement of the endocannabinoid system in the antihyperalgesic effect produced by the inhalation of CaEO in a post operative pain model...
September 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28914627/antinociceptive-effects-of-jwh015-in-female-and-male-rats
#4
Rebecca M Craft, Nicholas Z Greene, Alexa A Wakley
Despite greater chronic pain prevalence in females compared with males, and the analgesic potential of cannabinoid receptor type 2 (CB2) agonists, CB2 agonists have rarely been tested in females. The aim of the present study was to compare the antinociceptive effects of a CB2-preferring agonist, (2-methyl-1-propyl-1H-indol-3-yl)-1-naphthalenylmethanone (JWH015), in female and male rats against acute pain and persistent inflammatory pain. JWH015 (5-20 mg/kg, intraperitoneally) produced dose-dependent and time-dependent increases in latency to respond on the tail withdrawal and paw pressure tests that did not differ statistically between the sexes...
September 13, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28903355/anti-proliferative-pro-apoptotic-and-anti-invasive-effect-of-ec-ev-system-in-human-osteosarcoma
#5
Francesca Punzo, Chiara Tortora, Daniela Di Pinto, Iolanda Manzo, Giulia Bellini, Fiorina Casale, Francesca Rossi
Osteosarcoma is the most common and aggressive bone tumor in children. The Endocannabinoid/Endovanilloid system has been proposed as anticancer target in tumor of different origins. This system is composed of two receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel and their ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells. We investigated the effects of JWH-133 (CB2 agonist) and RTX (TRPV1 agonist) in six human Osteosarcoma cell lines: MG-63, U-2OS, MNNG/HOS, Saos-2, KHOS/NP, Hs888Lu, by Apoptosis and Migration-Assay...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28901432/effects-of-coadministration-of-low-dose-cannabinoid-type-2-receptor-agonist-and-morphine-on-vanilloid-receptor-1-expression-in-a-rat-model-of-cancer-pain
#6
Mingyue Zhang, Meng Chi, Huichao Zou, Songyu Tian, Zhaodi Zhang, Guonian Wang
Morphine is widely used as an analgesic to treat moderate to severe pain, but chronic morphine use is associated with development of tolerance and dependence, which limits its analgesic efficacy. Our previous research has showed that nonanalgetic dose of a cannabinoid type 2 (CB2) receptor agonist reduced morphine tolerance in cancer pain. A previous study showed the colocalization of CB2 and transient receptor potential vanilloid 1 (TRPV1) in human and rat dorsal root ganglia (DRG) sensory neurons. Whether coadministration of a CB2 receptor agonist and morphine could reduce TRPV1 expression in morphine‑induced antinociception and tolerance in cancer pain is unclear...
September 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28901271/the-role-of-cannabinoid-receptors-in-renal-diseases
#7
Hélène François, Lola Lecru
Chronic kidney disease (CKD) remains a major challenge for Public Health systems and corresponds to the replacement of renal functional tissue by extra-cellular matrix proteins such as collagens and fibronectin. There is no efficient treatment to date for CKD except nephroprotective strategies. The cannabinoid system and more specifically the cannabinoid receptors 1 (CB1) and 2 (CB2) may represent a new therapeutic target in CKD. Our review will first focus on the current state of knowledge regarding the cannabinoid system in normal renal physiology and in various experimental nephropathies, especially diabetes...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28899427/activation-of-dorsal-horn-cannabinoid-cb2-receptor-suppresses-the-expression-of-p2y12-and-p2y13-receptors-in-neuropathic-pain-rats
#8
Juan Niu, Dujuan Huang, Rui Zhou, MingXia Yue, Tao Xu, Junna Yang, Li He, Hong Tian, XiaoHong Liu, Junwei Zeng
BACKGROUND: More evidence suggests that dorsal spinal cord microglia is an important site contributing to CB2 receptor-mediated analgesia. The upregulation of P2Y12 and P2Y13 purinoceptors in spinal dorsal horn microglia is involved in the development of pain behavior caused by peripheral nerve injury. However, it is not known whether the expression of P2Y12 and P2Y13 receptors at spinal dorsal horn will be influenced after CB2 receptor activation in neuropathic pain rats. METHODS: Chronic constriction injury (CCI) and intrathecal ADPbetaS injection were performed in rats to induce neuropathic pain...
September 12, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28889355/tingenone-a-pentacyclic-triterpene-induces-peripheral-antinociception-due-to-cannabinoid-receptors-activation-in-mice
#9
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/28888955/distinct-roles-of-neuronal-and-microglial-cb2-cannabinoid-receptors-in-the-mouse-hippocampus
#10
Yong Li, Jimok Kim
The effects of cannabinoids are primarily mediated by type-1 cannabinoid receptors in the brain and type-2 cannabinoid receptors (CB2Rs) in the peripheral immune system. However, recent evidence demonstrates that CB2Rs are also expressed in the brain and implicated in neuropsychiatric effects. Diverse types of cells in various regions in the brain express CB2Rs but the cellular loci of CB2Rs that induce specific behavioral effects have not been determined. To manipulate CB2R expression in specific types of cells in the dorsal hippocampus of adult mice, we used Cre-dependent overexpression and CRISPR-Cas9 genome-editing techniques in combination with adeno-associated viruses and transgenic mice...
September 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28877641/collagen-and-hydroxyapatite-scaffolds-activate-distinct-osteogenesis-signaling-pathways-in-adult-adipose-derived-multipotent-stromal-cells
#11
Wei Duan, Masudul Haque, Michael T Kearney, Mandi Lopez
Osteogenic cell signaling pathway disruption varies among bone diseases. This investigation was designed to identify adipose derived multipotent stromal cell (ASC) and bone graft scaffold combinations for local, targeted restoration of gene expression and extracellular matrix (ECM) deposition. Human ASC osteogenesis on bone graft materials was quantified following culture in stromal (S), osteogenic (O) or osteogenic for 48 hours followed by stromal medium (OS) to test the two-part hypothesis: 1) Identical ASC isolates on distinct bone graft scaffolds demonstrate unique viability, differentiation, ECM production and gene expression in the same culture conditions; 2) Identical ASC-bone graft scaffold combinations have different cell viability, differentiation, ECM production, and gene expression when cultured in S, O or OS medium...
September 6, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28867485/mechanisms-of-action-of-cannabidiol-in-adoptively-transferred-experimental-autoimmune-encephalomyelitis
#12
Coral González-García, Irene Moreno Torres, Ruth García-Hernández, Lucía Campos-Ruíz, Luis Rodríguez Esparragoza, María José Coronado, Aranzazu García Grande, Antonio García-Merino, Antonio J Sánchez López
Cannabidiol (CBD) is one of the most important compounds in Cannabis sativa, lacks psychotropic effects, and possesses a high number of therapeutic properties including the amelioration of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyse the relative efficacy of CBD in adoptively transferred EAE (at-EAE), a model that allows better delineation of the effector phase of EAE. Splenocytes and lymph nodes from mice with actively induced EAE were cultured in the presence of MOG35-55 and IL-12 and inoculated intraperitoneally in recipient female C57BL/6J mice...
September 1, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28866072/changes-in-the-cannabinoids-receptors-in-rats-following-treatment-with-antidepressants
#13
Irena Smaga, Magdalena Zaniewska, Dawid Gawliński, Agata Faron-Górecka, Przemysław Szafrański, Marek Cegła, Małgorzata Filip
The endocannabinoid (eCB) system plays a significant role in the pathophysiology of depression. The potential participation of this system in the mechanism of action of antidepressants has been highlighted in recent years. The aim of this study was to investigate the expression of cannabinoid (CB) receptors using Western blot and CB1 receptor density using autoradiography after acute or chronic administration of antidepressant drugs [imipramine (IMI, 15mg/kg), escitalopram (ESC, 10mg/kg) and tianeptine (TIA, 10mg/kg)]...
September 1, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28861508/affinity-and-efficacy-studies-of-tetrahydrocannabinolic-acid-a-at-cannabinoid-receptor-types-one-and-two
#14
John M McPartland, Christa MacDonald, Michelle Young, Phillip S Grant, Daniel P Furkert, Michelle Glass
Introduction:Cannabis biosynthesizes Δ(9)-tetrahydrocannabinolic acid (THCA-A), which decarboxylates into Δ(9)-tetrahydrocannabinol (THC). There is growing interest in the therapeutic use of THCA-A, but its clinical application may be hampered by instability. THCA-A lacks cannabimimetic effects; we hypothesize that it has little binding affinity at cannabinoid receptor 1 (CB1). Materials and Methods: Purity of certified reference standards were tested with high performance liquid chromatography (HPLC). Binding affinity of THCA-A and THC at human (h) CB1 and hCB2 was measured in competition binding assays, using transfected HEK cells and [(3)H]CP55,940...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/28861504/cannabinoid-cb1-and-cb2-receptor-signaling-and-bias
#15
REVIEW
Mikkel Søes Ibsen, Mark Connor, Michelle Glass
An agonist that acts through a single receptor can activate numerous signaling pathways. Recent studies have suggested that different ligands can differentially activate these pathways by stabilizing a limited range of receptor conformations, which in turn preferentially drive different downstream signaling cascades. This concept, termed "biased signaling" represents an exciting therapeutic opportunity to target specific pathways that elicit only desired effects, while avoiding undesired effects mediated by different signaling cascades...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/28861501/palmitoylethanolamide-modulates-gpr55-receptor-signaling-in-the-ventral-hippocampus-to-regulate-mesolimbic-dopamine-activity-social-interaction-and-memory-processing
#16
Cecilia Kramar, Michael Loureiro, Justine Renard, Steven R Laviolette
Introduction: The GPR55 receptor has been identified as an atypical cannabinoid receptor and is implicated in various physiological processes. However, its functional role in the central nervous system is not currently understood. The presence of GPR55 receptor in neural regions such as the ventral hippocampus (vHipp), which is critical for cognition, recognition memory, and affective processing, led us to hypothesize that intra-vHipp GPR55 transmission may modulate mesolimbic activity states and related behavioral phenomena...
2017: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/28852269/cannabinoid-receptor-2-modulates-neutrophil-recruitment-in-a-murine-model-of-endotoxemia
#17
Theodore S Kapellos, Carlota Recio, David R Greaves, Asif J Iqbal
The endocannabinoid system consists of endogenous lipid mediators and cannabinoid receptors (CB) 1 and 2. It has previously been demonstrated that activation of the leukocyte-expressed CB2 has anti-inflammatory effects in vivo. Here, we report its role under baseline conditions and in a model of low-dose endotoxemia by comparing CB2 knockout to littermate control mice. CB2-deficient mice displayed significantly more neutrophils and fewer monocytes in the bone marrow under steady state. In initial validation experiments, administration of 1 mg/kg LPS to male C57BL/6J mice was shown to transiently upregulate systemic proinflammatory mediators (peaked at 2 hours) and mobilise bone marrow neutrophils and monocytes into circulation...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28843453/receptor-heteromer-mediated-regulation-of-endocannabinoid-signaling-in-activated-microglia-role-of-cb1-and-cb2-receptors-and-relevance-for-alzheimer-s-disease-and-levodopa-induced-dyskinesia
#18
Gemma Navarro, Dasiel Borroto-Escuela, Edgar Angelats, Íñigo Etayo, Irene Reyes-Resina, Marta Pulido-Salgado, Ana I Rodriguez-Perez, Enric I Canela, Josep Saura, José Luis Lanciego, José Luis Labandeira-García, Carlos A Saura, Kjell Fuxe, Rafael Franco
Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB1 and CB2 receptors, which may form heteromeric complexes (CB1-CB2Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoid receptors in resting and LPS/IFN-γ-activated microglia. Unlike CB1, CB2 receptors and CB1-CB2Hets were upregulated in activated microglia...
August 23, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28842619/pepcan-12-rvd-hemopressin-is-a-cb2-receptor-positive-allosteric-modulator-constitutively-secreted-by-adrenals-and-in-liver-upon-tissue-damage
#19
Vanessa Petrucci, Andrea Chicca, Sandra Glasmacher, Janos Paloczi, Zongxian Cao, Pal Pacher, Jürg Gertsch
Pepcan-12 (RVD-hemopressin; RVDPVNFKLLSH) is the major peptide of a family of endogenous peptide endocannabinoids (pepcans) shown to act as negative allosteric modulators (NAM) of cannabinoid CB1 receptors. Noradrenergic neurons have been identified to be a specific site of pepcan production. However, it remains unknown whether pepcans occur in the periphery and interact with peripheral CB2 cannabinoid receptors. Here, it is shown that pepcan-12 acts as a potent (K i value ~50 nM) hCB2 receptor positive allosteric modulator (PAM)...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28840279/bufalin-attenuates-cancer-induced-pain-and-bone-destruction-in-a-model-of-bone-cancer
#20
Dongxing Ji, Zhiyong Liang, Guixin Liu, Guangzong Zhao, Jun Fang
Bufalin is a natural anti-inflammatory small molecule. Given the close relationship between inflammation and cancer, many scholars have studied the effect of bufalin on cancer in vitro, but in vivo research is still lacking. A murine bone cancer model was used in this study. We conducted pain sensitive test on mice with bone cancer, by nocifensive behavior, mechanical allodynia, and thermal hyperalgesia. Serum levels of bone loss markers with bufalin treatment were measured by ELISA. Expressions of osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) were analyzed in bufalin-treated mice by real-time PCR and Western blot...
August 24, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
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