scholarly journals Cannabichromene is a cannabinoid CB2 receptor agonist

2018 ◽  
Author(s):  
Michael Udoh ◽  
Marina Santiago ◽  
Steven Devenish ◽  
Iain S. McGregor ◽  
Mark Connor
Keyword(s):  
Cell Surface ◽  
Receptor Agonist ◽  
Cannabinoid Receptors ◽  
Cellular Membrane ◽  
Cb2 Receptor ◽  
Surface Receptors ◽  
Cb2 Receptors ◽  
Cb2 Agonist ◽  
Cb1 And Cb2 Receptors

BACKGROUNDCannabichromene (CBC) is one of the most abundant phytocannabinoids in Cannabis spp. It has modest anti-nociceptive and anti-inflammatory effects and potentiates some effects of Δ9-tetrahydrocannabinol (THC) in vivo. How CBC exerts these effects is poorly defined and there is little information about its efficacy at cannabinoid receptors. We sought to determine the functional activity of CBC at CB1 and CB2 receptors.EXPERIMENTAL APPROACHAtT20 cells stably expressing HA-tagged human CB1 and CB2 receptors were used. Assays of cellular membrane potential and loss of cell surface receptors were performed.KEY RESULTSCBC activated CB2 but not CB1 receptors to produce a hyperpolarization of AtT20 cells. Activation of CB2 receptors was antagonised by the CB2 antagonist AM630 and sensitive to pertussis toxin. Co-application of CBC reduced activation of CB2 receptors CP55,940, a potent CB1 and CB2 agonist. Continuous CBC application induced loss of cell surface CB2 receptors and desensitisation of the CB2-induced hyperpolarization.CONCLUSIONS AND IMPLICATIONSCannabichromene is a selective CB2 receptor agonist displaying higher efficacy than THC in hyperpolarising AtT20 cells. CBC may contribute to the potential therapeutic effectiveness of some cannabis preparations, potentially through CB2-mediated modulation of inflammation.

scholarly journals Cannabinoid receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Mary Abood ◽  
Stephen P.H. Alexander ◽  
Francis Barth ◽  
Tom I. Bonner ◽  
Heather Bradshaw ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Receptor Agonist ◽  
Cannabinoid Receptors ◽  
Differential Susceptibility ◽  
Enzymatic Conversion ◽  
Cb2 Receptor ◽  
Endogenous Ligands ◽  
The Third ◽  
Cb2 Receptors ◽  
Cb1 And Cb2 Receptors

Cannabinoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Cannabinoid Receptors [107]) are activated by endogenous ligands that include N-arachidonoylethanolamine (anandamide), N-homo-γ-linolenoylethanolamine, N-docosatetra-7,10,13,16-enoylethanolamine and 2-arachidonoylglycerol. Potency determinations of endogenous agonists at these receptors are complicated by the possibility of differential susceptibility of endogenous ligands to enzymatic conversion [4].There are currently three licenced cannabinoid medicines each of which contains a compound that can activate CB1 and CB2 receptors [104]. Two of these medicines were developed to suppress nausea and vomiting produced by chemotherapy. These are nabilone (Cesamet®), a synthetic CB1/CB2 receptor agonist, and synthetic Δ9-tetrahydrocannabinol (Marinol®; dronabinol), which can also be used as an appetite stimulant. The third medicine, Sativex®, contains mainly Δ9-tetrahydrocannabinol and cannabidiol, both extracted from cannabis, and is used to treat multiple sclerosis and cancer pain.

CB2 cannabinoid receptor agonist selectively inhibits the mechanosensitivity of mucosal afferents in the guinea pig bladder.

2021 ◽  
Author(s):  
Stewart Christie ◽  
Vladimir P. Zagorodnyuk
Keyword(s):  
Guinea Pig ◽  
Receptor Agonist ◽  
Cannabinoid Receptors ◽  
Ex Vivo ◽  
Bladder Function ◽  
Electrophysiological Recording ◽  
Cb2 Receptor ◽  
Bladder Afferents ◽  
Cb2 Receptors

Bladder afferents play a pivotal role in bladder function such as urine storage and micturition, and conscious sensations such as urgency and pain. Endocannabinoids are ligands of cannabinoid receptors 1 and 2 (CB1 and CB2) but can influence activity of a variety of G-protein coupled receptors, and ligand- and voltage-gated channels. It is still not known which classes of bladder afferents are influenced by the CB1 and CB2 receptor agonists. This study aimed to determine the role of the CB2 receptors in two major classes of afferents in the guinea pig bladder, mucosal and muscular-mucosal. The mechanosensitivity of these two classes was determined by an ex vivo extracellular electrophysiological recording technique. A stable analogue of endocannabinoid anandamide, methanandamide (mAEA) potentiated the mechanosensitivity of mucosal bladder afferents in response to stroking. In the presence of TRPV1 antagonist (capsazepine), the effect of mAEA switched from excitatory to inhibitory. The selective CB2 receptor agonist, 4-quinolone-3-carboxyamide (4Q3C) significantly inhibited the mechanosensitivity of mucosal bladder afferents to stroking. In the presence of a CB2 receptor antagonist, the inhibitory effect of 4C3F was lost. mAEA and 4Q3C did not affect responses to stretch and/or mucosal stroking of muscular-mucosal afferents. Our findings revealed that agonists of the CB2 receptors selectively inhibited the mechanosensitivity of capsaicin-sensitive mucosal bladder afferents, but not muscular-mucosal afferents. This may have important implications for understanding of the role of endocannabinoids in modulating bladder function and sensation in health and diseases.

scholarly journals Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 827-838 ◽  
Author(s):  
Shuxian Jiang ◽  
Meritxell Alberich-Jorda ◽  
Radoslaw Zagozdzon ◽  
Kalindi Parmar ◽  
Yigong Fu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cell ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Bone Marrow Cells ◽  
Endocannabinoid System ◽  
Hematopoietic Stem ◽  
Cb2 Receptors ◽  
Cb2 Agonist

Abstract Endocannabinoids are arachidonic acid derivatives and part of a novel bioactive lipid signaling system, along with their G-coupled cannabinoid receptors (CB1 and CB2) and the enzymes involved in their biosynthesis and degradation. However, their roles in hematopoiesis and hematopoietic stem and progenitor cell (HSPC) functions are not well characterized. Here, we show that bone marrow stromal cells express endocannabinoids (anandamide and 2-arachidonylglycerol), whereas CB2 receptors are expressed in human and murine HSPCs. On ligand stimulation with CB2 agonists, CB2 receptors induced chemotaxis, migration, and enhanced colony formation of bone marrow cells, which were mediated via ERK, PI3-kinase, and Gαi-Rac1 pathways. In vivo, the CB2 agonist AM1241 induced mobilization of murine HSPCs with short- and long-term repopulating abilities. In addition, granulocyte colony-stimulating factor -induced mobilization of HSPCs was significantly decreased by specific CB2 antagonists and was impaired in Cnr2−/− cannabinoid type 2 receptor knockout mice. Taken together, these results demonstrate that the endocannabinoid system is involved in hematopoiesis and that CB2/CB2 agonist axis mediates repopulation of hematopoiesis and mobilization of HSPCs. Thus, CB2 agonists may be therapeutically applied in clinical conditions, such as bone marrow transplantation.

The role of the peripheral cannabinoid system in the pathogenesis of detrusor overactivity evoked by increased intravesical osmolarity in rats

2015 ◽  
Vol 93 (8) ◽  
pp. 721-726 ◽  
Author(s):  
Kajetan Juszczak ◽  
Piotr Maciukiewicz
Keyword(s):  
Urinary Bladder ◽  
Detrusor Overactivity ◽  
Cannabinoid Receptors ◽  
Bladder Capacity ◽  
Pressure Profile ◽  
Intravesical Instillation ◽  
Motility Index ◽  
Urinary Bladder Dysfunction ◽  
Cb2 Receptors ◽  
Cb1 And Cb2 Receptors

The cannabinoid receptors CB1 and CB2 are localized in the urinary bladder and play a role in the regulation of its function. We investigated the pathomechanisms through which hyperosmolarity induces detrusor overactivity (DO). We compared urinary bladder activity in response to blockade of CB1 and CB2 receptors using AM281 and AM630, respectively, in normal rats and after hyperosmolar stimulation. Experiments were performed on 44 rats. DO was induced by intravesical instillation of hyperosmolar saline. Surgical procedures and cystometry were performed under urethane anaesthesia. The measurements represent the average of 5 bladder micturition cycles. We analysed basal, threshold, and micturition voiding pressure; intercontraction interval; compliance; functional bladder capacity; motility index; and detrusor overactivity index. The blockage of CB1 and CB2 receptors diminished the severity of hyperosmolar-induced DO. In comparison with naïve animals the increased frequency of voiding with no significant effect on intravesical voiding pressure profile was observed as a result of the blockage of CB1 and CB2 receptors. These results demonstrate that hyperosmolar-induced DO is mediated by CB1 and CB2 receptors. Therefore, the cannabinoid pathway could potentially be a target for the treatment of urinary bladder dysfunction.

scholarly journals Early detachment of colon carcinoma cells during CD95(APO-1/Fas)-mediated apoptosis. I. De-adhesion from hyaluronate by shedding of CD44.

1996 ◽  
Vol 134 (4) ◽  
pp. 1089-1096 ◽  
Author(s):  
A R Günthert ◽  
J Sträter ◽  
U von Reyher ◽  
C Henne ◽  
S Joos ◽  
...  
Keyword(s):  
Cell Surface ◽  
Colon Carcinoma ◽  
Substantial Reduction ◽  
Carcinoma Cells ◽  
Surface Adhesion ◽  
Intact Cells ◽  
Surface Receptors ◽  
Colon Carcinoma Cells ◽  
Soluble Cd44

Ligation of CD95 (APO-1/Fas) cell surface receptors induces death in apoptosis-sensitive cells. Induction of apoptosis in adherent gamma interferon-stimulated HT-29 and COLO 205 colon carcinoma cells by cross-linking CD95 with anti-APO-1 monoclonal antibody resulted in detachment of the cells from hyaluronate starting about 1 h after antibody exposure. Loss of adhesion was paralleled by a substantial reduction of the multifunctional cell surface adhesion molecule CD44. As evidenced by cycloheximide treatment, this effect was not caused by impaired protein synthesis. Depletion of surface CD44 was also not due to membrane blebbing, since cytochalasin B failed to inhibit ascension from hyaluronate. Instead, ELISA and time kinetics showed increasing amounts of soluble CD44 in the supernatant of CD95-triggered cells. SDS-PAGE revealed that soluble CD44 had an apparent molecular mass of about 20 kD less than CD44 immunoprecipitated from intact cells. Thus, CD95-triggering induced shedding of CD44. Shedding is a novel mechanism operative in early steps of CD95-mediated apoptosis. Shedding surface molecules like CD44 might contribute to the active disintegration of dying epithelial cells in vivo.

Expression of Cannabinoid Receptors on the Neoplastic Lymphocytes in Patients with Chronic Lymphocytic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4804-4804
Author(s):  
Jaroslaw A. Piszcz ◽  
Miroslawa Pietruczuk ◽  
Janusz S. Kloczko ◽  
Milena Dabrowska ◽  
Marzenna Galar ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Peripheral Blood ◽  
Cannabinoid Receptors ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Neoplastic Cells ◽  
Fluorescent Intensity ◽  
Cb2 Receptors ◽  
Neoplastic Lymphocytes ◽  
Cb1 And Cb2 Receptors

Abstract Endocannabinoids take part in the physiology of neural and immune systems. The latest data showed that these compounds and their receptors play an important role in proliferation and apoptosis of various neoplastic cells. Cannabinoids were shown to increase apoptosis in human leukemia and lymphoma cell lines and culture of neoplastic cells obtained from patients with T-cell acute lymphoblastic leukemia. The aim of the study was an assessment of cannabinoid receptors expression on lymphocytes B derived from patients with CLL. The study group contains newly diagnosed, untreated adult patients with B-cell chronic lymphocytic leukemia; 13 male and 7 female, aged from 44 to 65. All of the patients were in B or C stage according to Binet. Peripheral blood samples from 10 healthy adult donors were used as the control group. The patients were hospitalized in the Department of Haematology, Medical University in Bialystok, Poland. Diagnosis of CLL in all cases was confirmed by routine immunophenotyping study. For flow cytometric analysis 1x105 – 1x106 of peripheral blood cells were incubated with 10ul of anty CB1 and anty CB2 polyclonal antibodies (American Diagnostics). Then 10ul of monoclonal antibodies IgG1-FITC and CD19-PE (Becton Dickinson) were added and the samples were incubated for 20 min in dark in 4°C. The samples were lysed, fixed and stabilized using Immuno-Prep (Coulter procedure) and assessed by flaw cytometry (Epics XL, Coulter). Statistical analysis was performed using non parametric U Mann-Whitney and Wilcoxon Tests. The conducted study revealed high expression of CB1 and CB2 receptors on the surface of neoplastic lymphocytes. The percentage of CB1/CD19 and CB2/CD19 positive cells in CLL patients were significantly higher, compared to the control group respectively (81.2±9,8% vs 12.0±9,3% p<0,05; 94,8±11,0 % vs 9,9±4,0%, p<0,05). No difference was noticed between the percentage of lymphocytes with CB1 and CB2 receptors expression in CLL and control group. Fluorescent intensity of CB2 receptors was about ten folds higher than CB1 receptors in both groups. The study demonstrated the presence of both types of cannabinoid receptors (CB1 and CB2) on neoplastic cells derived from patients with chronic lymphocytic leukemia. The higher percentage of B-lymphocytes expressing cannabinoid receptors in CLL patient suggests that the cannabinoid system may take part in CLL development. High intensity of CB2 receptor may be another target in CLL treatment.

Modulation and Functional Involvement of CB2 Peripheral Cannabinoid Receptors During B-Cell Differentiation

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3605-3615 ◽  
Author(s):  
Pierre Carayon ◽  
Jean Marchand ◽  
Danielle Dussossoy ◽  
Jean-Marie Derocq ◽  
Omar Jbilo ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Receptor Antagonist ◽  
Cannabinoid Receptors ◽  
Receptor Subtype ◽  
B Cell Differentiation ◽  
Cb2 Receptor ◽  
Cb2 Receptors ◽  
B Cell Subsets

Two subtypes of G-protein–coupled cannabinoid receptors have been identified to date: the CB1 central receptor subtype, which is mainly expressed in the brain, and the CB2 peripheral receptor subtype, which appears particularly abundant in the immune system. We investigated the expression of CB2 receptors in leukocytes using anti-CB2 receptor immunopurified polyclonal antibodies. We showed that peripheral blood and tonsillar B cells were the leukocyte subsets expressing the highest amount of CB2 receptor proteins. Dual-color confocal microscopy performed on tonsillar tissues showed a marked expression of CB2 receptors in mantle zones of secondary follicles, whereas germinal centers (GC) were weakly stained, suggesting a modulation of this receptor during the differentiation stages from virgin B lymphocytes to memory B cells. Indeed, we showed a clear downregulation of CB2 receptor expression during B-cell differentiation both at transcript and protein levels. The lowest expression was observed in GC proliferating centroblasts. Furthermore, we investigated the effect of the cannabinoid agonist CP55,940 on the CD40-mediated proliferation of both virgin and GC B-cell subsets. We found that CP55,940 enhanced the proliferation of both subsets and that this enhancement was blocked by the CB2 receptor antagonist SR 144528 but not by the CB1 receptor antagonist SR 141716. Finally, we observed that CB2 receptors were dramatically upregulated in both B-cell subsets during the first 24 hours of CD40-mediated activation. These data strongly support an involvement of CB2 receptors during B-cell differentiation.

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