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Cannabinoid receptors

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https://www.readbyqxmd.com/read/28433118/the-role-of-public-health-in-combatting-synthetic-cannabinoid-use-in-adolescents
#1
Katherine E Warren, Shirli Tay, Leana S Wen
As the country struggles to address an epidemic of alcohol and drug overdose, a wide-ranging category of chemical substances known as synthetic drugs have provoked a new sense of public urgency over the past decade. Synthetic cannabinoids, a heterogeneous and evolving set of synthetic compounds that act on endogenous cannabinoid receptors, have become particularly popular among adolescents due to their relative ease of access and reputation as a "legal high." The Baltimore City Health Department has worked to combat the recent surge in synthetic drug use through a major public awareness campaign, legislative reform, and retailer engagement and compliance initiative...
May 2017: Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine
https://www.readbyqxmd.com/read/28431968/cannabinoid-cb1-and-cb2-receptors-differentially-modulate-l-and-t-type-ca-2-channels-in-rat-retinal-ganglion-cells
#2
Wen-Jing Qian, Ning Yin, Feng Gao, Yanying Miao, Qian Li, Fang Li, Xing-Huai Sun, Xiong-Li Yang, Zhongfeng Wang
Endocannabinoid signaling system is involved in regulating multiple neuronal functions in the central nervous system by activating G-protein coupled cannabinoid CB1 and CB2 receptors (CB1Rs and CB2Rs). Growing evidence has shown that CB1Rs and CB2Rs are extensively expressed in retinal ganglion cells (RGCs). Here, modulation of L- and T-types Ca(2+) channels by activating CB1Rs and CB2Rs in RGCs was investigated. Triple immunofluorescent staining showed that L-type subunit CaV1.2 was co-localized with T-type subunits (CaV3...
April 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28428628/inflammatory-and-neuropathic-nociception-is-preserved-in-gpr55-knockout-mice
#3
Lawrence M Carey, Tannia Gutierrez, Liting Deng, Wan-Hung Lee, Ken Mackie, Andrea G Hohmann
The G-protein coupled receptor GPR55 has been postulated to serve as a novel cannabinoid receptor. A previous report indicated that GPR55 knockout mice fail to develop mechanical hyperalgesia, suggesting a pro-nociceptive role for GPR55 in the control of nociceptive responding. However, GPR55 knockout mice remain incompletely characterized in models of pathological pain. Here we provide a comprehensive assessment of responses of GPR55 knockout and wild-type mice to mechanical and thermal (heat, cold) stimulation in multiple, mechanistically distinct models of inflammatory and neuropathic pain...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428264/cb1-cannabinoid-receptor-drives-oocyte-maturation-and-embryo-development-via-pi3k-akt-and-mapk-pathways
#4
Angela Patricia López-Cardona, Serafín Pérez-Cerezales, Raúl Fernández-González, Ricardo Laguna-Barraza, Eva Pericuesta, Naiara Agirregoitia, Alfonso Gutiérrez-Adán, Ekaitz Agirregoitia
Endocannabinoids have been recognized as mediators of practically all reproductive events in mammals. However, little is known about the role of this system in oocyte maturation. In a mouse model, we observed that activation of the cannabinoid receptor (CB)1 during in vitro oocyte maturation modulated the phosphorylation status of Akt and ERK1/2 and enhanced the subsequent embryo production. In the absence of the CB1 receptor, in vivo oocyte maturation was impaired and embryo development delayed. The CB2 receptor was unable to rescue these effects...
April 20, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28426670/mice-expressing-a-hyper-sensitive-form-of-the-cb1-cannabinoid-receptor-cb1-show-modestly-enhanced-alcohol-preference-and-consumption
#5
David J Marcus, Angela N Henderson-Redmond, Maciej Gonek, Michael L Zee, Jill C Farnsworth, Randa A Amin, Mary-Jeanette Andrews, Brian J Davis, Ken Mackie, Daniel J Morgan
We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6%) but not higher concentrations of ethanol...
2017: PloS One
https://www.readbyqxmd.com/read/28425013/cannabinoids-as-modulators-of-cell-death-clinical-applications-and-future-directions
#6
B M Fonseca, N A Teixeira, G Correia-da-Silva
Endocannabinoids are bioactive lipids that modulate various physiological processes through G-protein-coupled receptors (CB1 and CB2) and other putative targets. By sharing the activation of the same receptors, some phytocannabinoids and a multitude of synthetic cannabinoids mimic the effects of endocannabinoids. In recent years, a growing interest has been dedicated to the study of cannabinoids properties for their analgesic, antioxidant, anti-inflammatory and neuroprotective effects. In addition to these well-recognized effects, various studies suggest that cannabinoids may affect cell survival, cell proliferation or cell death...
April 20, 2017: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/28422760/cannabinoid-cb1-receptor-overactivity-contributes-to-the-pathogenesis-of-idiopathic-pulmonary-fibrosis
#7
Resat Cinar, Bernadette R Gochuico, Malliga R Iyer, Tony Jourdan, Tadafumi Yokoyama, Joshua K Park, Nathan J Coffey, Hadass Pri-Chen, Gergő Szanda, Ziyi Liu, Ken Mackie, William A Gahl, George Kunos
Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease without effective treatment, highlighting the need for identifying new targets and treatment modalities. The pathogenesis of IPF is complex, and engaging multiple targets simultaneously might improve therapeutic efficacy. To assess the role of the endocannabinoid/cannabinoid receptor 1 (endocannabinoid/CB1R) system in IPF and its interaction with inducible nitric oxide synthase (iNOS) as dual therapeutic targets, we analyzed lung fibrosis and the status of the endocannabinoid/CB1R system and iNOS in mice with bleomycin-induced pulmonary fibrosis (PF) and in lung tissue and bronchoalveolar lavage fluid (BALF) from patients with IPF, as well as controls...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28421836/analytical-confirmation-of-synthetic-cannabinoids-in-a-cohort-of-179-presentations-with-acute-recreational-drug-toxicity-to-an-emergency-department-in-london-uk-in-the-first-half-of-2015
#8
Rachelle Abouchedid, Simon Hudson, Natalie Thurtle, Takahiro Yamamoto, James H Ho, George Bailey, Michelle Wood, Nele Sadones, Christophe P Stove, Alison Dines, John R H Archer, David M Wood, Paul I Dargan
CONTEXT: Synthetic cannabinoid receptor agonists are the largest group of new psychoactive substances reported in the last decade; in this study we investigated how commonly these drugs are found in patients presenting to the Emergency Department with acute recreational drug toxicity. METHODS: We conducted an observational cohort study enrolling consecutive adult patients presenting to an Emergency Department (ED) in London (UK) January-July 2015 (6 months) with acute recreational drug toxicity...
June 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28419871/short-term-inhibition-of-gabaergic-ipscs-induced-by-association-of-pre-and-postsynaptic-activation-in-the-neonatal-hippocampus
#9
Megumi Taketo, Hiroko Matsuda
Activity-dependent plasticity including short and long-term depression accompanied by a reduction in transmitter release probability has been demonstrated in both inhibitory and excitatory synapses. In the neonatal hippocampus, repetitive postsynaptic depolarization is followed by presynaptic alterations of the efficacy of GABAAergic transmission. Both facilitation and inhibition have been observed, but the mechanisms underlying this plasticity have not yet been elucidated. In the present experiment, repetitive postsynaptic depolarization by itself did not cause marked alterations of spontaneous inhibitory postsynaptic currents (sIPSCs)...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28417566/cannabinoid-type-1-receptor-cb1-bioligand-with-therapeutic-potential-for-withdrawal-syndrome-in-chemical-dependents-cannabis-sativa
#10
Lorane Hage Melim, Jaderson V Ferreira, Gisele A Chaves, Bianca L B Marino, Kessia P A Sousa, Lucilene R Souza, Maiara F B Brito, Hueldem R C Teixeira, Carlos H T P Silva, Cleydson B R Santos
Cannabis sativa withdrawal syndrome is characterized mainly by psychological symptoms. Using computational tools, the aim was to propose drug candidates based on natural ligands of the cannabinoid type 1 receptor (CB1), where only the molecule ZINC1730183 showed a positive prediction for the human CB1 receptor and easy synthetic prediction of accessibility. Therefore, this molecule proves to be a favorable proposal, suggesting the continuation of this research as a pharmacotherapeutic alternative to the withdrawal syndrome of C...
April 17, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28413023/a-chemoattractant-guided-walk-through-lymphopoiesis-from-hematopoietic-stem-cells-to-mature-b-lymphocytes
#11
Vivian Y Lim, Sandra Zehentmeier, Chris Fistonich, João P Pereira
B lymphocytes develop from hematopoietic stem cells (HSCs) in specialized bone marrow niches composed of rare mesenchymal lineage stem/progenitor cells (MSPCs) and sinusoidal endothelial cells. These niches are defined by function and location: MSPCs are mostly perisinusoidal cells that together with a small subset of sinusoidal endothelial cells express stem cell factor, interleukin-7 (IL-7), IL-15, and the highest amounts of CXCL12 in bone marrow. Though rare, MSPCs are morphologically heterogeneous, highly reticular, and form a vast cellular network in the bone marrow parenchyma capable of interacting with large numbers of hematopoietic cells...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28412921/synthetic-cannabinoids-psychopharmacology-clinical-aspects-and-psy-chotic-onset
#12
Giovanni Martinotti, Rita Santacroce, Duccio Papanti, Yasmine Elgharably, Mariya Prilutskaya, Ornella Corazza
Synthetic Cannabinoids (SC) are the widest and most diffused class of Novel Psychoactive Substances. SC are chemically heterogeneous and structurally dissimilar from delta-9-tetrahydrocannabinol, being full agonists of the endocannabinoid system receptors CB1 and CB2. Desired effects include euphoria, talkativeness, feelings of joy and laughter, relaxation. With respect to cannabis, SC intake may also be associated with quicker arise of the effects, shorter duration of action, and larger levels of hangover...
April 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28412500/the-major-neurotransmitter-systems-in-the-basolateral-amygdala-and-the-ventral-tegmental-area-mediate-morphine-induced-memory-consolidation-impairment
#13
Khadijeh Alsadat Sharifi, Ameneh Rezayof, Anahita Torkaman-Boutorabi, Mohammad-Reza Zarrindast
In the present study, we investigated the possible participation of the endocannabinoid system in the basolateral amygdala and NMDA or GABA-A receptor neurotransmission in the ventral tegmental area in the memory consolidation impairment induced by morphine administration. To measure memory formation, step-through type passive avoidance apparatus was used with adult male Wistar rats. The results showed that intraperitoneal (i.p.) administration of morphine (3 and 6 mg/kg) after the successful training phase had an amnestic effect and induced memory consolidation impairment...
April 12, 2017: Neuroscience
https://www.readbyqxmd.com/read/28409931/1-4-18-f-fluorobenzyl-4-tetrahydrofuran-2-yl-methyl-piperazine-a-novel-suitable-radioligand-with-low-lipophilicity-for-imaging-sigma-1-receptors-in-the-brain
#14
Yingfang He, Fang Xie, Jiajun Ye, Winnie Deuther-Conrad, Bixiao Cui, Liang Wang, Jie Lu, Jörg Steinbach, Peter Brust, Yiyun Huang, Jie Lu, Hongmei Jia
We have designed and synthesized novel piperazine compounds with low lipophilicity as σ1 receptor ligands. 1-(4-Fluorobenzyl)-4-((tetrahydrofuran-2-yl)methyl)piperazine (10) possessed low nanomolar σ1 receptor affinity and high selectivity toward the vesicular acetylcholine transporter (>2000-fold), σ2 receptors (52-fold), adenosine A2A, adrenergic α2, cannabinoid CB1, dopamine D1, D2L, γ-aminobutyric acid A (GABAA), NMDA, melatonin MT1, MT2 and serotonin 5-HT1 receptors. The corresponding radiotracer [(18)F]10 demonstrated high brain uptake and extremely high brain-to-blood ratios in biodistribution studies in mice...
April 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28408985/new-drugs-in-psychiatry-focus-on-new-pharmacological-targets
#15
REVIEW
Filippo Caraci, Gian Marco Leggio, Salvatore Salomone, Filippo Drago
The approval of psychotropic drugs with novel mechanisms of action has been rare in recent years. To address this issue, further analysis of the pathophysiology of neuropsychiatric disorders is essential for identifying new pharmacological targets for psychotropic medications. In this report, we detail drug candidates being examined as treatments for psychiatric disorders. Particular emphasis is placed on agents with novel mechanisms of action that are being tested as therapies for depression, schizophrenia, or Alzheimer's disease...
2017: F1000Research
https://www.readbyqxmd.com/read/28404451/anandamide-and-2-ag-are-endogenously-present-within-the-laterodorsal-tegmental-nucleus-functional-implications-for-a-role-of-ecbs-in-arousal
#16
Neeraj Soni, Bala Krishna Prabhala, Ved Mehta, Osman Mirza, Kristi Anne Kohlmeier
Previously, we presented electrophysiological evidence for presence in mice brain slices of functional cannabinoid type I receptors (CB1Rs) within the laterodorsal tegmentum (LDT), a brain stem nucleus critical in control of arousal and rapid eye movement (REM) sleep. Further, using pharmacological agents, we provided data suggestive of the endogenous presence of cannabinoids (CBs) acting at LDT CB1Rs. However, in those studies, we were unable to identify the type(s) of CB ligands endogenously present in the LDT, and this information has not been provided elsewhere...
April 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28402427/bdnf-overexpression-prevents-cognitive-deficit-elicited-by-adolescent-cannabis-exposure-and-host-susceptibility-interaction
#17
Hadar Segal-Gavish, Neta Gazit, Yael Barhum, Tali Ben-Zur, Michal Taler, Shay Henry Hornfeld, Irit Gil-Ad, Abraham Weizman, Inna Slutsky, Minae Niwa, Atsushi Kamiya, Akira Sawa, Daniel Offen, Ran Barzilay
Cannabis abuse in adolescence is associated with increased risk of psychotic disorders. Δ-9-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. Disrupted-In-Schizophrenia-1 (DISC1) protein is a driver for major mental illness by influencing neurodevelopmental processes. Here, utilizing a unique mouse model based on host (DISC1) X environment (THC administration) interaction, we aimed at studying the pathobiological basis through which THC exposure elicits psychiatric manifestations...
April 11, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28400256/n-oleoyldopamine-modulates-activity-of-midbrain-dopaminergic-neurons-through-multiple-mechanisms
#18
Olga A Sergeeva, Roberto De Luca, Karolina Mazur, Aissa N Chepkova, Helmut L Haas, Andreas Bauer
N-oleoyl-dopamine (OLDA) is an amide of dopamine and oleic acid, synthesized in catecholaminergic neurons. The present study investigates OLDA targets in midbrain dopaminergic (DA) neurons. Substantia Nigra compacta (SNc) DA neurons recorded in brain slices were excited by OLDA in wild type mice. In transient receptor potential vanilloid 1 (TRPV1) knockout (KO) mice, however, SNc DA neurons displayed sustained inhibition of firing. In the presence of the dopamine type 2 receptor (D2R) antagonist sulpiride or the dopamine transporter blocker nomifensine no such inhibition was observed...
April 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28398245/molecular-targets-for-pet-imaging-of-activated-microglia-the-current-situation-and-future-expectations
#19
REVIEW
Claire Tronel, Bérenger Largeau, Maria Joao Santiago Ribeiro, Denis Guilloteau, Anne-Claire Dupont, Nicolas Arlicot
Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals' binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28393558/supraventricular-tachycardia-and-acute-confusion-following-ingestion-of-e-cigarette-fluid-containing-ab-fubinaca-and-adb-fubinaca-a-case-report-with-quantitative-analysis-of-serum-drug-concentrations
#20
Rex Pui Kin Lam, Magdalene Huen Yin Tang, Siu Chung Leung, Yeow Kuan Chong, Matthew Sik Hon Tsui, Tony Wing Lai Mak
BACKGROUND: AB-FUBINACA and ADB-FUBINACA are structurally similar synthetic cannabinoids with potent CB1 receptor agonistic effects. Very little is known about their pharmacology and toxicology. OBJECTIVE: To report a case of supraventricular tachycardia and acute confusion after ingestion of e-cigarette fluid containing AB-FUBINACA and ADB-FUBINACA, with quantitative analysis of the serum drug concentrations. CASE REPORT: A healthy 24-year-old man ingested two drops of e-cigarette fluid which were later found to contain AB-FUBINACA and ADB-FUBINACA...
April 10, 2017: Clinical Toxicology
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