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https://www.readbyqxmd.com/read/29627825/effect-of-cb1-ligands-on-neurogenic-and-myogenic-contractile-responses-in-the-guinea-pig-ileum
#1
Josef Donnerer, Ingrid Liebmann
This study aimed at investigating whether the synthetic cannabinoid receptor agonist (+)-WIN 55212-2 has neurogenic and myogenic relaxant effects on the longitudinal muscle-myenteric plexus (LMMP) strip of the guinea-pig ileum. (+)-WIN 55212-2, 1-1,000 nmol/L, concentration-dependently inhibited both the electrical stimulation-induced cholinergic twitch responses as well as the myogenic smooth muscle contractions in the LMMP preparation. SR-141716A (rimonabant) 1-1,000 nmol/L, the cannabinoid CB1 receptor antagonist, being without effect on its own, antagonized the (+)-WIN 55212-2-induced effects...
April 6, 2018: Pharmacology
https://www.readbyqxmd.com/read/29626639/assessing-the-real-time-activation-of-the-cannabinoid-cb1-receptor-and-the-associated-structural-changes-using-a-fret-biosensor
#2
Ying Liu, Lu-Yao Chen, Hong Zeng, Richard Ward, Nan Wu, Li Ma, Xi Mu, Qiu-Lan Li, Yang Yang, Su An, Xiao-Xi Guo, Qian Hao, Tian-Rui Xu
The cannabinoid receptor 1 (CB1) is mainly expressed in the nervous system and regulates learning, memory processes, pain and energy metabolism. However, there is no way to directly measure its activation. In this study, we constructed a CB1 intramolecular fluorescence resonance energy transfer (FRET) sensor, which could measure CB1 activation by monitoring structural changes between the third intracellular loop and the C-terminal tail. CB1 agonists induced a time- and concentration-dependent increase in the FRET signal, corresponding to a reduction in the distance between the third intracellular loop and the C-terminal tail...
April 4, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29624642/cannabidiol-regulates-behavioural-alterations-and-gene-expression-changes-induced-by-spontaneous-cannabinoid-withdrawal
#3
Francisco Navarrete, Auxiliadora Aracil-Fernández, Jorge Manzanares
BACKGROUND AND PURPOSE: Cannabidiol (CBD) represents a promising therapeutic tool for treating cannabis use disorder (CUD). This study aimed to evaluate the effects of CBD on the behavioural and gene expression alterations induced by spontaneous cannabinoid withdrawal. EXPERIMENTAL APPROACH: Spontaneous cannabinoid withdrawal was evaluated 12 h after cessation of CP-55,940 treatment (0.5 mg·kg-1 /12 h; intraperitoneally (i.p.); 7 days) in C57BL/6J mice. The effects of CBD (5, 10 and 20 mg·kg-1 ; i...
April 6, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29618679/low-risk-of-pulmonary-vein-stenosis-after-contemporary-atrial-fibrillation-ablation-lessons-from-repeat-procedures-after-radiofrequency-current-cryoballoon-and-laser-balloon
#4
Takahiko Nagase, Stefano Bordignon, Laura Perrotta, Fabrizio Bologna, Felix K Weise, Athanasios Konstantinou, Ritsushi Kato, Boris Schmidt, Julian K R Chun
BACKGROUND: The incidence of pulmonary vein stenosis (PVS) after AF ablation following contemporary procedures remains unclear. We compared the incidence of PVS/narrowing (PVS/N) after PV isolation (PVI) for (1) 3-D mapping-guided wide-area encircling irrigated radiofrequency current (RFC) ablation; (2) first-third-generation big cryoballoon (CB1-3) ablation; and (3) laser balloon (LB) ablation.Methods and Results:All patients undergoing a second procedure between January 2012 and November 2016 were subgrouped according to index ablation (PVI): RFC; CB; or LB...
April 5, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29615900/peripheral-cb1-receptor-neutral-antagonist-am6545-ameliorates-hypometabolic-obesity-and-improves-adipokine-secretion-in-monosodium-glutamate-induced-obese-mice
#5
Haiming Ma, Guina Zhang, Chunrong Mou, Xiujuan Fu, Yadan Chen
Effect of peripheral cannabinoid receptor 1 (CB1R) blockade by AM6545 in the monosodium glutamate (MSG)-induced hypometabolic and hypothalamic obesity was observed, and the impact on intraperitoneal adipose tissue and adipokines was investigated. The MSG mice is characterized by excessive abdominal obesity, and combined with dyslipidemia and insulin resistance. 3-Week AM6545 treatment dose-dependently decreased the body weight, intraperitoneal fat mass, and rectified the accompanied dyslipidemia include elevated serum triglyceride, total cholesterol, free fatty acids, and lowered LDLc level...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29607411/verbal-memory-performance-and-reduced-cortical-thickness-of-brain-regions-along-the-uncinate-fasciculus-in-young-adult-cannabis-users
#6
Nina Levar, Alan N Francis, Matthew J Smith, Wilson C Ho, Jodi M Gilman
Introduction: Memory impairment is one of the most commonly reported effects of cannabis use, especially among those who initiate use earlier, perhaps due to the effects of delta-9- tetrahydrocannabinol on cannabinoid (CB1) receptors in the brain. Studies have increasingly investigated whether cannabis use is associated with impairments in verbal memory, and with alterations in brain structures underlying verbal memory. The uncinate fasciculus (UF), a long-range white matter tract, connects regions with densely localized CB1 receptors that are important in verbal memory...
2018: Cannabis and Cannabinoid Research
https://www.readbyqxmd.com/read/29601300/cannabinoids-in-health-and-disease-pharmacological-potential-in-metabolic-syndrome-and-neuroinflammation
#7
REVIEW
Andrea Mastinu, Marika Premoli, Giulia Ferrari-Toninelli, Simone Tambaro, Giuseppina Maccarinelli, Maurizio Memo, Sara Anna Bonini
The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena. In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving. Moreover, cannabinoid agonists are able to reduce inflammatory response...
March 30, 2018: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/29596901/periaqueductal-gray-glutamatergic-cannabinoid-and-vanilloid-receptor-interplay-in-defensive-behavior-and-aversive-memory-formation
#8
Franklin P Back, Antonio P Carobrez
Stimulation of the midbrain periaqueductal gray matter (PAG) in humans elicits sensations of fear and impending terror, and mediates predator defensive responses in rodents. In rats, pharmacological stimulation of the dorsolateral portion of the PAG (dlPAG) with N-Methyl-d-Aspartate (NMDA) induces aversive conditioning that acts as an unconditioned stimulus (US). In the present work, we investigated the interplay between the vanilloid TRPV1 and cannabinoid CB1 receptors in the NMDA-dlPAG defensive response and in subsequent aversive learning...
March 26, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29595540/sex-specific-differences-in-cannabinoid-induced-extracellular-signal-regulated-kinase-phosphorylation-in-the-cingulate-cortex-prefrontal-cortex-and-nucleus-accumbens-of-lister-hooded-rats
#9
Michela Rosas, Simona Porru, Valentina Giugliano, Silvia Antinori, Simona Scheggi, Paola Fadda, Walter Fratta, Elio Acquas, Liana Fattore
Sex-dependent differences have been consistently described in cannabinoid addiction research. In particular, we recently reported that female Lister Hooded rats display greater self-administration of the cannabinoid CB1 receptor agonist WIN55,212-2 (WIN) and stronger reinstatement of cannabinoid-seeking behavior than males. Cannabinoids modulate the phosphorylation of the extracellular-signal-regulated kinase (ERK) pathway, leading to various forms of plasticity-related learning that likely affect operant behavior...
March 27, 2018: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29580129/bidirectional-influence-of-amygdala-%C3%AE-1-adrenoceptors-blockade-on-cannabinoid-signaling-in-contextual-and-auditory-fear-memory
#10
Mohammad Nasehi, Saman Shahbazzadeh, Mohaddeseh Ebrahimi-Ghiri, Mohammad-Reza Zarrindast
The basolateral amygdala (BLA) is a major target and modulator of stress and has a critical role in the neural circuitry presenting learned fear behaviors. On the other hand, both the endocannabinoid and noradrenergic systems may be involved in regulating the stress responses, fear, and anxiety. Considering the aforementioned, we have investigated the involvement of the BLA β1 -adrenoceptors in conditioned fear responses induced by ACPA, a CB1 receptor (CB1R) agonist. In adult male NMRI mice, freezing responses to context and cue were measured using a Pavlovian fear conditioning apparatus...
March 1, 2018: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/29574689/targeting-glial-cb-2-receptors-to-delay-the-progression-of-the-pathological-phenotype-in-tdp-43-a315t-transgenic-mice-a-model-of-amyotrophic-lateral-sclerosis
#11
Francisco Espejo-Porras, Laura García-Toscano, Carmen Rodríguez-Cueto, Irene Santos-García, Eva de Lago, Javier Fernández-Ruiz
BACKGROUND AND PURPOSE: CB2 receptors up-regulate in reactive microglia in the spinal cord of TDP-43(A315T) transgenic mice, an experimental model of ALS. To determine whether such up-regulation may be pharmacologically exploited, we investigated different treatments modulating the CB2 receptor function. EXPERIMENTAL APPROACH: We treated TDP-43(A315T) transgenic mice with the non-selective agonist WIN55,212-2, alone or combined with selective CB1 or CB2 antagonists, as well as with the selective CB2 agonist HU-308, and evaluated their effects on the pathological phenotype...
March 25, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29574668/cannabidiol-reverses-deficits-in-hippocampal-ltp-in-a-model-of-alzheimer-s-disease
#12
Blathnaid Hughes, Caroline E Herron
Here we demonstrate for the first time that cannabidiol (CBD) acts to protect synaptic plasticity in an in vitro model of Alzheimer's disease (AD). The non-psycho active component of Cannabis sativa, CBD has previously been shown to protect against the neurotoxic effects of beta amyloid peptide (Aβ) in cell culture and cognitive behavioural models of neurodegeneration. Hippocampal long-term potentiation (LTP) is an activity dependent increase in synaptic efficacy often used to study cellular mechanisms related to memory...
March 24, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29574098/inhibition-of-mitochondrial-permeability-transition-pore-opening-contributes-to-cannabinoid-type-1-receptor-agonist-acea-induced-neuroprotection
#13
Lei Ma, Wen Niu, Shuai Yang, Junbin Tian, Hanlin Luan, Ming Cao, Wenbin Xi, Weifeng Tu, Ji Jia, Jianrui Lv
Cannabinoid type 1 (CB1) receptor agonist arachidonyl-2-chloroethylamide (ACEA) induces neuroprotection against brain ischemia, and the mechanism, however, is still elusive. In this study, we used bilateral common carotid artery occlusion (BCCAO) in mice and oxygen-glucose deprivation (OGD) in primary cultured neurons to mimic brain ischemic injury, and hypothesized that cannabinoid CB1 receptor agonist ACEA protects ischemic neurons via inhibiting the opening of mitochondrial permeability transition pore (MPTP)...
March 21, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29570673/protective-effects-of-gomisin-n-against-hepatic-cannabinoid-type-1-receptor-induced-insulin-resistance-and-gluconeogenesis
#14
Arulkumar Nagappan, Dae Young Jung, Ji-Hyun Kim, Myeong Ho Jung
Activation of the hepatic cannabinoid type 1 receptor (CB1R) induces insulin resistance and gluconeogenesis via endoplasmic reticulum (ER) stress, thereby contributing to hyperglycemia. Gomisin N (GN) is a phytochemical derived from Schisandra chinensis . In the current study, we investigated the inhibitory effects of GN on hepatic CB1R-mediated insulin resistance and gluconeogenesis in 2-arachidonoylglycerol (AG; an agonist of CB1R)-treated HepG2 cells and in high-fat diet (HFD)-induced obese mice. Treatment with 2-AG induced the expression of ER stress markers, serine/threonine phosphatase PHLPP1 , Lipin1 , and ceramide synthesis genes, but reduced the expression of ceramide degradation genes in HepG2 cells...
March 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29562280/the-use-of-cannabinoids-in-colitis-a-systematic-review-and-meta-analysis
#15
Daniel G Couch, Henry Maudslay, Brett Doleman, Jonathan N Lund, Saoirse E O'Sullivan
Background: Clinical trials investigating the use of cannabinoid drugs for the treatment of intestinal inflammation are anticipated secondary to preclinical literature demonstrating efficacy in reducing inflammation. Methods: We systematically reviewed publications on the benefit of drugs targeting the endo-cannabinoid system in intestinal inflammation. We collated studies examining outcomes for meta-analysis from EMBASE, MEDLINE and Pubmed until March 2017. Quality was assessed according to mSTAIR and SRYCLE score...
March 19, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29556136/secondary-metabolites-isolated-from-pinus-roxburghii-and-interpretation-of-their-cannabinoid-and-opioid-binding-properties-by-virtual-screening-and-in-vitro-studies
#16
Rola M Labib, Radhakrishnan Srivedavyasasri, Fadia S Youssef, Samir A Ross
Pinus roxburghii is highly popular as a potent analgesic and anti-inflammatory agent; however its exact mechanism of action was not fully elucidated. We aimed to interpret the analgesic and anti-inflammatory activity of the total ethanol extract of Pinus roxburghii bark (PRE) and its isolated compounds by both in silico molecular modelling and in-vitro cannabinoid and opioid binding activities evaluation for the first time. Comprehensive phytochemical investigation of PRE resulted in the isolation of sixteen compounds that were fully elucidated using1 H NMR and13 C NMR...
March 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/29552078/isolation-and-biological-evaluation-of-prenylated-flavonoids-from-maclura-pomifera
#17
Yerkebulan Orazbekov, Mohamed A Ibrahim, Serjan Mombekov, Radhakrishnan Srivedavyasasri, Ubaidilla Datkhayev, Bauyrzhan Makhatov, Narayan D Chaurasiya, Babu L Tekwani, Samir A Ross
Phytochemical analysis of the ethanolic extract of Maclura pomifera fruits yielded four new compounds ( I - IV ) along with eleven known compounds ( V - XV ). The crude extract exhibited significant activity towards cannabinoid receptors (CB1: 103.4% displacement; CB2: 68.8% displacement) and possibly allosteric interaction with δ and μ opioid receptors (-49.7 and -53.8% displacement, resp.). Compound I was found to be possibly allosteric for κ and μ opioid receptors (-88.4 and -27.2% displacement, resp...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29551963/cannabinoid-receptors-modulate-excitation-of-an-olfactory-bulb-local-circuit-by-cortical-feedback
#18
Frederic Pouille, Nathan E Schoppa
Recent studies have provided evidence that corticofugal feedback (CFF) from the olfactory cortex to the olfactory bulb (OB) can significantly impact the state of excitation of output mitral cells (MCs) and tufted cells (TCs) and also modulate neural synchrony. Interpreting these effects however has been complicated by the large number of cell targets of CFF axons in the bulb. Within the granule cell layer (GCL) alone, CFF axons target both GABAergic granule cells (GCs) as well as GABAergic deep short-axon cells (dSACs) that inhibit GCs...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29551733/impacts-of-cannabinoid-receptor-ligands-on-nicotine-and-chronic-mild-stress-induced-cognitive-and-depression-like-effects-in-mice
#19
Karolina Pekala, Agnieszka Michalak, Marta Kruk-Slomka, Barbara Budzynska, Grazyna Biala
Taking into account the rather frequent concomitance of nicotine abuse and stress, we aimed to research memory- and depression-related effects of nicotine administration in combination with chronic mild unpredictable stress (CMUS) in mice and an involvement of the endocannabinoid system through CB1 and CB2 receptors. Mice were submitted to the CMUS for 4 weeks. Effects on depression-like behaviors and cognition, exerted by a combined administration of CB1, i.e., Oleamide (2.5, 5.0 mg/kg), AM 251 (0.1, 0.25 mg/kg) and CB2, i...
March 15, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29549157/molecular-and-behavioral-pharmacological-characterization-of-abused-synthetic-cannabinoids-mmb-and-mdmb-fubinaca-mn-18-nnei-cumyl-pica-and-5-fluoro-cumyl-pica
#20
Thomas F Gamage, Charlotte E Farquhar, Timothy W Lefever, Julie A Marusich, Richard C Kevin, Iain S McGregor, Jenny L Wiley, Brian F Thomas
Synthetic cannabinoids are a class of novel psychoactive substances that exhibit high affinity at the cannabinoid type-1 (CB1) receptor and produce effects similar to those of THC, the primary psychoactive constituent of cannabis. Illicit drug manufacturers are continually circumventing laws banning the sale of synthetic cannabinoids by synthesizing novel structures and doing so with little regard for their potential impact on pharmacological and toxicological effects. Synthetic cannabinoids produce a wide range of effects including cardiotoxicity, seizure activity, and kidney damage and can result in death...
March 16, 2018: Journal of Pharmacology and Experimental Therapeutics
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