scholarly journals Imaging Cannabinoid Receptors: A Brief Collection of Covalent and Fluorescent Probes for CB1 and CB2 Receptors

2021 ◽  
Author(s):  
Alexander J. Hamilton ◽  
Alan D. Payne ◽  
Mauro Mocerino ◽  
Hendra Gunosewoyo
Keyword(s):  
Fluorescent Probes ◽  
Cannabinoid Receptors ◽  
Cb2 Receptors ◽  
Cb1 And Cb2 Receptors

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.

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.

GPR55 – a putative “type 3” cannabinoid receptor in inflammation

2016 ◽  
Vol 27 (3) ◽  
Author(s):  
Hyewon Yang ◽  
Juan Zhou ◽  
Christian Lehmann
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Signaling System ◽  
Broad Distribution ◽  
Potential Therapeutic Target ◽  
Cellular Processes ◽  
Cb2 Receptors ◽  
Type 3 ◽  
G Protein Coupled ◽  
Cb1 And Cb2 Receptors

AbstractG protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor. Therefore, GPR55 has emerged as a putative “type 3” cannabinoid receptor, establishing a novel class of cannabinoid receptor. Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.

The Potential Benefits of Palmitoylethanolamide in Palliation: A Qualitative Systematic Review

2019 ◽  
Vol 36 (12) ◽  
pp. 1134-1154
Author(s):  
Mellar P. Davis ◽  
Bertrand Behm ◽  
Zankhana Mehta ◽  
Carlos Fernandez
Keyword(s):  
Systematic Review ◽  
Cannabinoid Receptors ◽  
Randomized Trials ◽  
Streptococcal Infections ◽  
Qualitative Systematic Review ◽  
Potential Benefits ◽  
Egg Yolks ◽  
Cb2 Receptors ◽  
Poor Children ◽  
Cb1 And Cb2 Receptors

Palmitoylethanolamide (PEA) is a nutraceutical endocannabinoid that was retrospectively discovered in egg yolks. Feeding poor children with known streptococcal infections prevented rheumatic fever. Subsequently, it was found to alter the course of influenza. Unfortunately, there is little known about its pharmacokinetics. Palmitoylethanolamide targets nonclassical cannabinoid receptors rather than CB1 and CB2 receptors. Palmitoylethanolamide will only indirectly activate classical cannabinoid receptors by an entourage effect. There are a significant number of prospective and randomized trials demonstrating the pain-relieving effects of PEA. There is lesser evidence of benefit in patients with nonpain symptoms related to depression, Parkinson disease, strokes, and autism. There are no reported drug–drug interactions and very few reported adverse effects from PEA. Further research is needed to define the palliative benefits to PEA.

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.

scholarly journals Diverse chemotypes drive biased signaling by cannabinoid receptors

2020 ◽  
Author(s):  
Tamara Miljuš ◽  
Franziska M. Heydenreich ◽  
Thais Gazzi ◽  
Atsushi Kimbara ◽  
Mark Rogers-Evans ◽  
...  
Keyword(s):  
G Protein ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Endocannabinoid System ◽  
Receptor System ◽  
Biased Signaling ◽  
Cb2 Receptors ◽  
Regulatory Functions ◽  
Functional Mechanisms ◽  
Cb1 And Cb2 Receptors

AbstractCannabinoid CB1 and CB2 receptors are members of the G protein-coupled receptor family, which is the largest class of membrane proteins in the human genome. As part of the endocannabinoid system, they have many regulatory functions in the human body. Their malfunction therefore triggers a diverse set of undesired conditions, such as pain, neuropathy, nephropathy, pruritus, osteoporosis, cachexia and Alzheimer’s disease. Although drugs targeting the system exist, the molecular and functional mechanisms involved are still poorly understood, preventing the development of better therapeutics with fewer undesired effects. One path toward the development of better and safer medicines targeting cannabinoid receptors relies on the ability of some compounds to activate a subset of pathways engaged by the receptor while sparing or even inhibiting the others, a phenomenon known as biased signaling. To take advantage of this phenomenon for drug development, a better profiling of the pathways engaged by the receptors is required. Using a BRET-based signaling detection platform, we systematically analyzed the primary signaling cascades activated by CB1 and CB2 receptors, including 9 G protein and 2 β-arrestin subtypes. Given that biased signaling is driven by ligand-specific distinct active conformations of the receptor, establishing a link between the signaling profiles elicited by different drugs and their chemotypes may help designing compounds that selectively activate beneficial pathways while avoiding those leading to undesired effects. We screened a selection of 35 structurally diverse ligands, including endocannabinoids, phytocannabinoids and synthetic compounds structurally similar or significantly different from natural cannabinoids. Our data show that biased signaling is a prominent feature of the cannabinoid receptor system and that, as predicted, ligands with different chemotypes have distinct signaling profiles. The study therefore allows for better understanding of cannabinoid receptors signaling and provides the information about tool compounds that can now be used to link signaling pathways to biological outcomes, aiding the design of improved therapeutics.

scholarly journals Cannabinoid Receptors in Myocardial Injury: A Brother Born to Rival

2021 ◽  
Vol 22 (13) ◽  
pp. 6886
Author(s):  
Xinru Tang ◽  
Zheng Liu ◽  
Xiaoqing Li ◽  
Jing Wang ◽  
Liliang Li
Keyword(s):  
Immune System ◽  
Myocardial Injury ◽  
Cannabinoid Receptors ◽  
The Central Nervous System ◽  
Cb2 Receptors ◽  
Myocardial Injuries ◽  
Receptor Modulators ◽  
Cb1 And Cb2 Receptors

Cannabinoid receptors typically include type 1 (CB1) and type 2 (CB2), and they have attracted extensive attention in the central nervous system (CNS) and immune system. Due to more in-depth studies in recent years, it has been found that the typical CB1 and CB2 receptors confer functional importance far beyond the CNS and immune system. In particular, many works have reported the critical involvement of the CB1 and CB2 receptors in myocardial injuries. Both pharmacological and genetic approaches have been used for studying CB1 and CB2 functions in these studies, revealing that the brother receptors have many basic differences and sometimes antagonistic functions in a variety of myocardial injuries, despite some sequence or location identity they share. Herein, we introduce the general differences of CB1 and CB2 cannabinoid receptors, and summarize the functional rivalries between the two brother receptors in the setting of myocardial injuries. We point out the importance of individual receptor-based modulation, instead of dual receptor modulators, when treating myocardial injuries.

scholarly journals WIN55,212-2, a Dual Modulator of Cannabinoid Receptors and G Protein-Coupled Inward Rectifier Potassium Channels

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 484
Author(s):  
Dongchen An ◽  
Steve Peigneur ◽  
Jan Tytgat
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
G Protein ◽  
Cannabinoid Receptors ◽  
Inward Rectifier ◽  
Xenopus Laevis Oocyte ◽  
Inward Rectifier Potassium Channels ◽  
Wide Range ◽  
Cb2 Receptors ◽  
G Protein Coupled

The coupling of cannabinoid receptors, CB1 and CB2, to G protein-coupled inward rectifier potassium channels, GIRK1 and GIRK2, modulates neuronal excitability in the human brain. The present study established and validated the functional expression in a Xenopus laevis oocyte expression system of CB1 and CB2 receptors, interacting with heteromeric GIRK1/2 channels and a regulator of G protein signaling, RGS4. This ex vivo system enables the discovery of a wide range of ligands interacting orthosterically or allosterically with CB1 and/or CB2 receptors. WIN55,212-2, a non-selective agonist of CB1 and CB2, was used to explore the CB1- or CB2-GIRK1/2-RGS4 signaling cascade. We show that WIN55,212-2 activates CB1 and CB2 at low concentrations whereas at higher concentrations it exerts a direct block of GIRK1/2. This illustrates a dual modulatory function, a feature not described before, which helps to explain the adverse effects induced by WIN55,212-2 in vivo. When comparing the effects with other typical cannabinoids such as Δ9-THC, CBD, CP55,940, and rimonabant, only WIN55,212-2 can significantly block GIRK1/2. Interestingly, the inward rectifier potassium channel, IRK1, a non-G protein-coupled potassium channel important for setting the resting membrane voltage and highly similar to GIRK1 and GIRK2, is not sensitive to WIN55,212-2, Δ9-THC, CBD, CP55,940, or rimonabant. From this, it is concluded that WIN55,212-2 selectively blocks GIRK1/2.

Enhanced Humoral Immunity in Mice Lacking CB1 and CB2 Receptors (Cnr1 −/− /Cnr2 −/− Mice) is not Due to Increased Splenic Noradrenergic Neuronal Activity

2014 ◽  
Vol 9 (4) ◽  
pp. 544-557 ◽  
Author(s):  
Tyrell Simkins ◽  
Robert B. Crawford ◽  
John L. Goudreau ◽  
Keith J. Lookingland ◽  
Barbara L. F. Kaplan
Keyword(s):  
Neuronal Activity ◽  
Humoral Immunity ◽  
Cb2 Receptors ◽  
Cb1 And Cb2 Receptors
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