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https://www.readbyqxmd.com/read/28925883/novel-therapeutics-in-glaucoma-management
#1
Claudio Bucolo, Chiara Bianca Maria Platania, Filippo Drago, Michele Reibaldi, Vincenza Bonfiglio, Teresio Avitabile, Maurizio Uva
Glaucoma is a progressive optic neuropathy characterized by retinal ganglion cell death and alterations of visual field. Elevated intraocular pressure (IOP) is considered the main risk factor of glaucoma, even though other factors cannot be ruled out, such as epigenetic mechanisms. An overview of the ultimate promising experimental drugs to manage glaucoma has been provided. In particular, we have focused on purinergic ligands, KATP channel activators, gases (nitric oxide, carbon monoxide and hydrogen sulfide), non-glucocorticoid steroidal compounds, neurotrophic factors, PI3K/Akt activators, citicoline, histone deacetylase inhibitors, cannabinoids, dopamine and serotonin receptors ligands, small interference RNA, and Rho kinase inhibitors...
September 15, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28921757/the-neurobiological-bases-of-autism-spectrum-disorders-the-r451c-neuroligin-3-mutation-hampers-the-expression-of-long-term-synaptic-depression-in-the-dorsal-striatum
#2
Giuseppina Martella, Maria Meringolo, Laura Trobiani, Antonella De Jaco, Antonio Pisani, Paola Bonsi
Autism spectrum disorders (ASDs) comprise a heterogeneous group of disorders with a complex genetic etiology. Current theories on the pathogenesis of ASDs suggest that they might arise from an aberrant synaptic transmission affecting specific brain circuits and synapses. The striatum, which is part of the basal ganglia circuit, is one of the brain regions involved in ASDs. Mouse models of ASDs have provided evidence for an imbalance between excitatory and inhibitory neurotransmission. Here we investigated the expression of long-term synaptic plasticity at corticostriatal glutamatergic synapses in the dorsal striatum of the R451C-NL3 phenotypic mouse model of autism...
September 16, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28921125/exogenous-cannabinoid-efficacy-merely-a-pharmacokinetic-interaction
#3
Jennifer H Martin, Jennifer Schneider, Catherine J Lucas, Peter Galettis
Endocannabinoid pharmacology is now relatively well understood with a number of endocannabinoids and endogenous cannabinoid neurotransmitters identified and the pharmacokinetics relatively well ascertained. Further, the cannabinoid receptors are now molecularly and pharmacologically characterised and the cell processes involved in endocannabinoid transcription, synthesis, post-translational modification and protein expression are reported. Endogenous cannabinoids have been shown to have key roles in immune and pain pathways and neuro-behavioural signalling including appetite regulation...
September 18, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28918320/in-silico-interaction-analysis-of-cannabinoid-receptor-interacting-protein-1b-crip1b-cb1-cannabinoid-receptor
#4
Pratishtha Singh, Anjali Ganjiwale, Allyn C Howlett, Sudha M Cowsik
Cannabinoid Receptor Interacting Protein isoform 1b (CRIP1b) is known to interact with the CB1 receptor. Alternative splicing of the CNRIP1 gene produces CRIP1a and CRIP1b with a difference in the third exon only. Exons 1 and 2 encode for a functional domain in both proteins. CRIP1a is involved in regulating CB1 receptor internalization, but the function of CRIP1b is not very well characterized. Since there are significant identities in functional domains of these proteins, CRIP1b is a potential target for drug discovery...
September 6, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28916833/inhibition-of-wnt-%C3%AE-catenin-pathway-and-histone-acetyltransferase-activity-by-rimonabant-a-therapeutic-target-for-colon-cancer
#5
Maria Chiara Proto, Donatella Fiore, Chiara Piscopo, Silvia Franceschelli, Valentina Bizzarro, Chiara Laezza, Gianluigi Lauro, Alessandra Feoli, Alessandra Tosco, Giuseppe Bifulco, Gianluca Sbardella, Maurizio Bifulco, Patrizia Gazzerro
In a high percentage (≥85%) of both sporadic and familial adenomatous polyposis forms of colorectal cancer (CRC), the inactivation of the APC tumor suppressor gene initiates tumor formation and modulates the Wnt/β-Catenin transduction pathways involved in the control of cell proliferation, adhesion and metastasis. Increasing evidence showed that the endocannabinoids control tumor growth and progression, both in vitro and in vivo. We evaluated the effect of Rimonabant, a Cannabinoid Receptor 1 (CB1) inverse agonist, on the Wnt/β-Catenin pathway in HCT116 and SW48 cell lines carrying the genetic profile of metastatic CRC poorly responsive to chemotherapies...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28914627/antinociceptive-effects-of-jwh015-in-female-and-male-rats
#6
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/28913816/re-visiting-the-endocannabinoid-system-and-its-therapeutic-potential-in-obesity-and-associated-diseases
#7
REVIEW
Joyce M Richey, Orison Woolcott
PURPOSE OF REVIEW: The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism. RECENT FINDINGS: Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects...
September 14, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28912087/endocannabinoid-mechanism-in-amphetamine-type-stimulant-use-disorders-a-short-review
#8
REVIEW
Hang Su, Min Zhao
Recent evidence shows that the endocannabinoid system is involved in amphetamine-type stimulants (ATS) use disorders. To elucidate the role of the endocannabinoid system in ATS addiction, we reviewed results of studies using cannabinoid receptor agonists, antagonists as well as knockout model. The endocannabinoid system seems to play a role in reinstatement and relapse of ATS addiction and ATS-induced psychiatric symptoms. The molecular mechanisms of this system remains unclear, the association with dopamine system in nucleus accumbens is most likely involved...
September 11, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28905873/cardiovascular-effects-of-marijuana-and-synthetic-cannabinoids-the-good-the-bad-and-the-ugly
#9
REVIEW
Pal Pacher, Sabine Steffens, György Haskó, Thomas H Schindler, George Kunos
Dysregulation of the endogenous lipid mediators endocannabinoids and their G-protein-coupled cannabinoid receptors 1 and 2 (CB1R and CB2R) has been implicated in a variety of cardiovascular pathologies. Activation of CB1R facilitates the development of cardiometabolic disease, whereas activation of CB2R (expressed primarily in immune cells) exerts anti-inflammatory effects. The psychoactive constituent of marijuana, Δ(9)-tetrahydrocannabinol (THC), is an agonist of both CB1R and CB2R, and exerts its psychoactive and adverse cardiovascular effects through the activation of CB1R in the central nervous and cardiovascular systems...
September 14, 2017: Nature Reviews. Cardiology
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
#10
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
#11
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
#12
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/28895540/polymorphism-rs3123554-in-the-cannabinoid-receptor-gene-type-2-cnr2-reveals-effects-on-body-weight-and-insulin-resistance-in-obese-subjects
#13
Daniel Antonio de Luis, Olatz Izaola, David Primo, Beatriz de la Fuente, Rocio Aller
BACKGROUND: Few studies assessing the relationship between single nucleotide polymorphisms in CNR2 and obesity or its related metabolic parameters are available. OBJECTIVE: To investigate the influence of polymorphism rs3123554 in the CNR2 receptor gene on obesity anthropometric parameters, insulin resistance, and adipokines in subjects with obesity. DESIGN: The study population consisted of 1027 obese subjects, who were performed bioelectrical impedance analyses, blood pressure measurements, serial assessments of dietary intake during three days, and biochemical tests...
October 2017: Endocrinología, diabetes y nutrición
https://www.readbyqxmd.com/read/28889355/tingenone-a-pentacyclic-triterpene-induces-peripheral-antinociception-due-to-cannabinoid-receptors-activation-in-mice
#14
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/28888984/cannabidiol-a-novel-inverse-agonist-for-gpr12
#15
Kevin J Brown, Alyssa S Laun, Zhao-Hui Song
GPR12 is a constitutively active, Gs protein-coupled receptor that currently has no confirmed endogenous ligands. GPR12 may be involved in physiological processes such as maintenance of oocyte meiotic arrest and brain development, as well as pathological conditions such as metastatic cancer. In this study, the potential effects of various classes of cannabinoids on GPR12 were tested using a cAMP accumulation assay. Our data demonstrate that cannabidiol (CBD), a major non-psychoactive phytocannabinoid, acted as an inverse agonist to inhibit cAMP accumulation stimulated by the constitutively active GPR12...
September 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28888955/distinct-roles-of-neuronal-and-microglial-cb2-cannabinoid-receptors-in-the-mouse-hippocampus
#16
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/28887229/mapk-activation-patterns-of-at1r-and-cb1r-in-shr-versus-wistar-astrocytes-evidence-of-cb1r-hypofunction-and-crosstalk-between-at1r-and-cb1r
#17
Dhanush Haspula, Michelle A Clark
BACKGROUND: Angiotensin (Ang) II and cannabinoids regulate physiologically relevant astroglial functions via receptor-mediated activation of Mitogen-activated protein kinases (MAPKs). In this study, we investigated the consequences of astroglial Ang II type 1 receptor (AT1R) and Cannabinoid type 1 receptor (CB1R) activation, alone and in combination, on MAPK activation in the presence and absence of hypertensive states. In addition, we also investigated a novel unidirectional crosstalk mechanism between AT1R and CB1R, that involves PKC-mediated phosphorylation of CB1R...
September 5, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28885457/cannabis-constituent-synergy-in-a-mouse-neuropathic-pain-model
#18
Sherelle L Casey, Nicholas Atwal, Christopher W Vaughan
Cannabis and its psychoactive constituent Δ9-tetrahydrocannabinol (THC) have efficacy against neuropathic pain however, this is hampered by their side-effects. It has been suggested that co-administration with another major constituent cannabidiol (CBD) might enhance the analgesic actions of THC and minimise its deleterious side-effects. We examined the basis for this phytocannabinoid interaction in a mouse chronic constriction injury (CCI) model of neuropathic pain. Acute systemic administration of THC dose-dependently reduced CCI-induced mechanical and cold allodynia, but also produced motor incoordination, catalepsy and sedation...
September 1, 2017: Pain
https://www.readbyqxmd.com/read/28879802/anti-nociceptive-interactions-between-opioids-and-a-cannabinoid-receptor-2-agonist-in-inflammatory-pain
#19
Matthew B Yuill, David E Hale, Josée Guindon, Daniel J Morgan
The cannabinoid 1 receptor and cannabinoid 2 receptor can both be targeted in the treatment of pain; yet, they have some important differences. Cannabinoid 1 receptor is expressed at high levels in the central nervous system, whereas cannabinoid 2 receptor is found predominantly, although not exclusively, outside the central nervous system. The objective of this study was to investigate potential interactions between cannabinoid 2 receptor and the mu-opioid receptor in pathological pain. The low level of adverse side effects and lack of tolerance for cannabinoid 2 receptor agonists are attractive pharmacotherapeutic traits...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28877641/collagen-and-hydroxyapatite-scaffolds-activate-distinct-osteogenesis-signaling-pathways-in-adult-adipose-derived-multipotent-stromal-cells
#20
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
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