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CB1 and CB2 receptors

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https://www.readbyqxmd.com/read/29792186/involvement-of-the-cb-2-cannabinoid-receptor-in-cell-growth-inhibition-and-g0-g1-cell-cycle-arrest-via-the-cannabinoid-agonist-win-55-212-2-in-renal-cell-carcinoma
#1
Mohammed I Khan, Anna A Sobocińska, Klaudia K Brodaczewska, Katarzyna Zielniok, Malgorzata Gajewska, Claudine Kieda, Anna M Czarnecka, Cezary Szczylik
BACKGROUND: The anti-tumor properties of cannabinoids have been investigated in many in vitro and in vivo studies. Many of these anti-tumor effects are mediated via cannabinoid receptor types 1 and 2 (CB1 and CB2 ), comprising the endocannabinoid system (ECS). In this study, we investigated the ECS based on CB 1 and CB 2 receptor gene and protein expression in renal cell carcinoma (RCC) cell lines. In view of their further use for potential treatments, we thus investigated the roles of CB1 and CB2 receptors in the anti-proliferative action and signal transduction triggered by synthetic cannabinoid agonists [such as JWH-133 and WIN 55,212-2 (WIN-55)] in RCC cell lines...
May 23, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29773016/is-cannabidiol-a-promising-substance-for-new-drug-development-a-review-of-its-potential-therapeutic-applications
#2
Nida Noreen, Faqir Muhammad, Bushra Akhtar, Farooq Azam, Muhammad Irfan Anwar
The pharmacological importance of cannabidiol (CBD) has been in study for several years. CBD is the major nonpsychoactive constituent of plant Cannabis sativa and its administration is associated with reduced side effects. Currently, CBD is undergoing a lot of research which suggests that it has no addictive effects, good safety profile and has exhibited powerful therapeutic potential in several vital areas. It has wide spectrum of action because it acts through endocannabinoid receptors; CB1 and CB2 and it also acts on other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2...
2018: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/29770478/the-endocannabinoid-alcohol-crosstalk-recent-advances-on-a-bi-faceted-target
#3
REVIEW
Gianluca Lavanco, Valentina Castelli, Anna Brancato, Giuseppe Tringali, Fulvio Plescia, Carla Cannizzaro
Increasing evidence focuses on the endocannabinoid system as a relevant player in the induction of aberrant synaptic plasticity and related addictive phenotype following chronic excessive alcohol drinking. Besides, the endocannabinoid system is implicated in the pathogenesis of alcoholic liver disease. Interestingly, whereas the involvement of CB1 cannabinoid receptors in alcohol rewarding properties is established, the central and peripheral action of CB2 cannabinoid signalling is still to be elucidated. This review aims at giving the input to deepen knowledge on the role of the endocannabinoid system, highlighting the advancing evidence that suggests that CB1 and CB2 receptors may play opposite roles in the regulation of both the reinforcing properties of alcohol in the brain and the mechanisms responsible for cell injury and inflammation in the hepatic tissue...
May 16, 2018: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29765535/effects-of-cb2-and-trpv1-receptors-stimulation-in-pediatric-acute-t-lymphoblastic-leukemia
#4
Francesca Punzo, Iolanda Manzo, Chiara Tortora, Elvira Pota, Velia D' Angelo, Giulia Bellini, Alessandra Di Paola, Federica Verace, Fiorina Casale, Francesca Rossi
T-Acute Lymphoblastic Leukemia (T-ALL) is less frequent than B-ALL, but it has poorer outcome. For this reason new therapeutic approaches are needed to treat this malignancy. The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G-Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzymes. CB1 is expressed mainly in central nervous system while CB2 predominantly on immune and peripheral cells, therefore we chose to selectively stimulate CB2 and TRPV1...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29759062/inhibition-of-2-ag-hydrolysis-differentially-regulates-blood-brain-barrier-permeability-after-injury
#5
Justin R Piro, Georgette L Suidan, Jie Quan, YeQing Pi, Sharon M O'Neill, Marissa Ilardi, Nikolay Pozdnyakov, Thomas A Lanz, Hualin Xi, Robert D Bell, Tarek A Samad
BACKGROUND: Acute neurological insults caused by infection, systemic inflammation, ischemia, or traumatic injury are often associated with breakdown of the blood-brain barrier (BBB) followed by infiltration of peripheral immune cells, cytotoxic proteins, and water. BBB breakdown and extravasation of these peripheral components into the brain parenchyma result in inflammation, oxidative stress, edema, excitotoxicity, and neurodegeneration. These downstream consequences of BBB dysfunction can drive pathophysiological processes and play a substantial role in the morbidity and mortality of acute and chronic neurological insults, and contribute to long-term sequelae...
May 14, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29754307/effects-of-cocaine-self-administration-and-its-extinction-on-the-rat-brain-cannabinoid-cb1-and-cb2-receptors
#6
Beata Bystrowska, Małgorzata Frankowska, Irena Smaga, Lucyna Pomierny-Chamioło, Małgorzata Filip
The aim of this study was to evaluate changes in the expression of cannabinoid type 1 (CB1) and 2 (CB2) receptor proteins in several brain regions in rats undergoing cocaine self-administration and extinction training. We used a triad-yoked procedure to distinguish between the motivational and pharmacological effects of cocaine. Using immunohistochemistry, we observed a significant decrease in CB1 receptor expression in the prefrontal cortex, dorsal striatum, and the basolateral and basomedial amygdala following cocaine (0...
May 12, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29740328/emerging-role-of-endo-cannabinoids-in-migraine
#7
REVIEW
Pinja Leimuranta, Leonard Khiroug, Rashid Giniatullin
In this mini-review, we summarize recent discoveries and present new hypotheses on the role of cannabinoids in controlling trigeminal nociceptive system underlying migraine pain. Individual sections of this review cover key aspects of this topic, such as: (i) the current knowledge on the endocannabinoid system (ECS) with emphasis on expression of its components in migraine related structures; (ii) distinguishing peripheral from central site of action of cannabinoids, (iii) proposed mechanisms of migraine pain and control of nociceptive traffic by cannabinoids at the level of meninges and in brainstem, (iv) therapeutic targeting in migraine of monoacylglycerol lipase and fatty acid amide hydrolase, enzymes which control the level of endocannabinoids; (v) dual (possibly opposing) actions of cannabinoids via anti-nociceptive CB1 and CB2 and pro-nociceptive TRPV1 receptors...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29669714/cannabidiol-inhibits-endocannabinoid-signaling-in-autaptic-hippocampal-neurons
#8
Alex Straiker, Michaela Dvorakova, Anaelle Zimmowitch, Ken P Mackie
Δ9-THC and cannabidiol (CBD) are two main cannabinoid constituents of marijuana and hashish. The pharmacology of Δ9-THC has been extensively studied, while our understanding of the pharmacology of CBD has remained limited, despite excitement in CBD's potential role in treating certain pediatric epilepsies and its reputation for attenuating some Δ9-THC-induced effects. It was established early on that CBD binds poorly to the orthosteric site of CB1 or CB2 cannabinoid receptors and its actions were commonly attributed to other non-cannabinoid receptor mechanisms...
April 18, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/29662438/cannabinoid-receptor-type-1-expression-in-the-developing-avian-retina-morphological-and-functional-correlation-with-the-dopaminergic-system
#9
Luzia da Silva Sampaio, Regina C C Kubrusly, Yolanda P Colli, Priscila P Trindade, Victor T Ribeiro-Resende, Marcelo Einicker-Lamas, Roberto Paes-de-Carvalho, Patricia F Gardino, Fernando G de Mello, Ricardo A De Melo Reis
The avian retina has been used as a model to study signaling by different neuro- and gliotransmitters. It is unclear how dopaminergic and cannabinoid systems are related in the retina. Here we studied the expression of type 1 and 2 cannabinoid receptors (CB1 and CB2 ), as well as monoacylglycerol lipase (MAGL), the enzyme that degrades 2-arachidonoylglycerol (2-AG), during retina development. Our data show that CB1 receptor is highly expressed from embryonic day 5 (E5) until post hatched day 7 (PE7), decreasing its levels throughout development...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29624642/cannabidiol-regulates-behavioural-alterations-and-gene-expression-changes-induced-by-spontaneous-cannabinoid-withdrawal
#10
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/29601300/cannabinoids-in-health-and-disease-pharmacological-potential-in-metabolic-syndrome-and-neuroinflammation
#11
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/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
#12
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/29556136/secondary-metabolites-isolated-from-pinus-roxburghii-and-interpretation-of-their-cannabinoid-and-opioid-binding-properties-by-virtual-screening-and-in-vitro-studies
#13
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 using 1 H NMR and 13 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
#14
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/29551733/impacts-of-cannabinoid-receptor-ligands-on-nicotine-and-chronic-mild-stress-induced-cognitive-and-depression-like-effects-in-mice
#15
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
#16
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 Δ-9-tetrahydrocannabinol (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 the potential impact on pharmacological and toxicological effects. Synthetic cannabinoids produce a wide range of effects that include cardiotoxicity, seizure activity, and kidney damage, and they can cause death...
May 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29547827/pharmacological-characterization-of-the-cannabinoid-receptor-2-agonist-%C3%AE-caryophyllene-on-seizure-models-in-mice
#17
Jana Tchekalarova, Keylla da Conceição Machado, Antonio Luiz Gomes Júnior, Ana Amélia de Carvalho Melo Cavalcante, Albena Momchilova, Rumyana Tzoneva
PURPOSE: Activation of CB1 receptors, produces anticonvulsant effect accompanied by memory disturbance both in animal seizure tests and in patients with epilepsy. Few reports considered the role of CB2 receptor on seizure susceptibility and cognitive functions. The aim of the present study was to explore the effect of a selective CB2 receptor agonist β-caryophyllene (BCP) in models of seizures and cognition in mice. METHODS: Dose-dependent effects of BCP was studied in maximal electroshock seizure (MES) test, subcutaneous pentylenetetrazole (scPTZ) test and Morris water maze test...
April 2018: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29546501/cannabinoid-receptors-mental-pain-and-suicidal-behavior-a-systematic-review
#18
REVIEW
Laura Colino, Javier Herranz-Herrer, Elena Gil-Benito, Teresa Ponte-Lopez, Pablo Del Sol-Calderon, Maria Rodrigo-Yanguas, María Gil-Ligero, Antonio J Sánchez-López, Jose de Leon, Hilario Blasco-Fontecilla
PURPOSE OF REVIEW: The current serotonin-based biological model of suicidal behavior (SB) may be too simplistic. There is emerging evidence that other biomarkers and biological systems may be involved in SB pathophysiology. The literature on the endocannabinoid (EC) systems and SB is limited. The objective of the present article is to review all available information on the relationship between cannabinoid receptors (CB1 and CB2 receptors), and SB and/or psychological pain. RECENT FINDINGS: Our review is limited by the small number and heterogeneity of studies identified: (1) an autopsy study describing elevated levels of CB1 receptor activity in the prefrontal cortex and suicide in both depression and alcoholism and (2) studies supporting the involvement of both CB1 and CB2 receptors in the regulation of neuropathic pain and stress-induced analgesia...
March 15, 2018: Current Psychiatry Reports
https://www.readbyqxmd.com/read/29540562/monoacylglycerol-lipase-inhibitors-reverse-paclitaxel-induced-nociceptive-behavior-and-proinflammatory-markers-in-a-mouse-model-of-chemotherapy-induced-neuropathy
#19
Zachary Curry, Jenny Wilkerson, Deniz Bagdas, Sarah Kyte, Nipa Patel, Giulia Donvito, Mohammed A Mustafa, Justin Poklis, Micah Niphakis, Ku-Lung Hsu, Benjamin F Cravatt, David A Gewirtz, M Imad Damaj, Aron H Lichtman
Although paclitaxel effectively treats various cancers, its debilitating peripheral neuropathic pain side effects often persist long after treatment has ended. Therefore, a compelling need exists for the identification of novel pharmacologic strategies to mitigate this condition. As inhibitors of monoacylglycerol lipase (MAGL), the primary hydrolytic enzyme of the endogenous cannabinoid 2-arachidonyolglycerol, produce antinociceptive effects in numerous rodent models of pain, we investigated whether inhibitors of this enzyme (i...
March 14, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29528965/evaluation-of-different-drug-classes-on-transient-sciatic-nerve-injury-depressed-marble-burying-in-mice
#20
Jenny L Wilkerson, Zachary A Curry, Pamela D Kinlow, Brittany L Mason, Ku-Lung Hsu, Mario van der Stelt, Benjamin F Cravatt, Aron H Lichtman
A great need exists for the identification of new effective analgesics to treat sustained pain. However, most preclinical nociceptive assays measure behavioral responses evoked by noxious stimuli (ie, pain-stimulated behavior), which presents a challenge to distinguish between motor impairing and antinociceptive effects of drugs. Here, we demonstrate that chronic constriction injury (CCI) of the sciatic nerve elicits common pain-stimulated responses (ie, mechanical allodynia and thermal hyperalgesia) as well as reduces marble burying/digging behaviors that occur during the early stages of the neuropathy and resolve within 1 week...
June 2018: Pain
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