CB-2

PURPOSE: In patients with paroxysmal atrial fibrillation (PAF), functional changes are observed in the left atrium (LA) after pulmonary vein isolation (PVI) procedure. Although previous studies have investigated the altered mechanical functions of the LA with radiofrequency (RF) ablation, changes in the LA functions in the early period after cryoablation (CB-2) have not been clearly demonstrated. This study aims to explore the early periodical changes in mechanical functions of the LA in patients with PAF who underwent CB-2 based ablation through the help of echocardiographic methods which contain Doppler and strain parameters...

Background: N-linoleyltyrosine (NITyr), one of the anandamide analogs, exerts activity via the endocannabinoid receptors (CB1 and CB2 ), which showed anti-tumor effects in various tumors. Therefore, we speculated that NITyr might show anti-non-small cell lung cancer (NSCLC) effects via the CB1 or CB2 receptor. The purpose of the investigation was to reveal the anti-tumor ability of NITyr on A549 cells and its mechanisms. Methods: The viability of A549 cells was measured by MTT assay, and the cell cycle and apoptosis were both examined by flow cytometry; in addition, cell migration was tested by wound healing assay...

Nabilone, a synthetic analogue of delta-9-Tetrahydrocannabinol, is an agonist of cannabinoid receptors (CB-1 and CB-2) approved to treat chemotherapy-induced vomiting refractory to antiemetics. Its use in patients with refractory vomiting due to gastrointestinal dysmotility (GID) has not been reported. Our study aims are to assess nabilone usefulness and side-effects in patients with refractory vomiting due to GID. Patients prescribed nabilone at St. Mark's intestinal rehabilitation unit (January 2017 to September 2022) due to GID vomiting have been retrospectively reviewed...

CB2 cannabinoid receptor agonists suppress pathological pain in animal models and lack unwanted side effects commonly associated with direct activation of CB1 receptors. However, the types of pain most responsive to CB2 agonists are incompletely understood and cell types which underlie CB2 -mediated therapeutic efficacy remain largely unknown. We previously reported that the CB2 receptor agonist LY2828360 reduced neuropathic nociception induced by toxic challenge with chemotherapeutic and anti-retroviral agents in mice...

Synthetic cannabinoid receptor agonists (SCRAs) constitute the largest and most defiant group of abuse designer drugs. These new psychoactive substances (NPS), developed as unregulated alternatives to cannabis, have potent cannabimimetic effects and their use is usually associated with episodes of psychosis, seizures, dependence, organ toxicity and death. Due to their ever-changing structure, very limited or nil structural, pharmacological, and toxicological information is available to the scientific community and the law enforcement offices...

Pathological remodeling of atrial tissue renders the atria more prone to arrhythmia upon arrival of electrical triggers. Activation of the renin-angiotensin system is an important factor that contributes to atrial remodeling, which may result in atrial hypertrophy and prolongation of P-wave duration. In addition, atrial cardiomyocytes are electrically coupled via gap junctions, and electrical remodeling of connexins may result in dysfunction of coordinated wave propagation within the atria. Currently, there is a lack of effective therapeutic strategies that target atrial remodeling...

Diet-induced obesity (DIO) is a contributor to co-morbidities, resulting in alterations in hormones, lipids, and low-grade inflammation, with the cannabinoid type 2 receptor (CB2 ) contributing to the inflammatory response. The effects of modulating CB2 with pharmacological treatments on inflammation and adaptations to the obese state are not known. Therefore, we aimed to investigate the molecular mechanisms in adipose tissue of CB2 agonism and CB2 antagonism treatment in a DIO model. Male Sprague Dawley rats were placed on a high-fat diet (HFD) (21% fat) for 9 weeks, then received daily intraperitoneal injections with a vehicle, AM630 (0...

Mast cells (MCs) are the main participants in the control of immune reactions associated with inflammation, allergies, defense against pathogens, and tumor growth. Bioactive lipids are lipophilic compounds able to modulate MC activation. Here, we explored some of the effects of the bioactive lipid lysophosphatidylinositol (LPI) on MCs. Utilizing murine bone marrow-derived mast cells (BMMCs), we found that LPI did not cause degranulation, but slightly increased FcεRI-dependent β-hexosaminidase release...

As a common joint disease, osteoarthritis (OA) is often associated with chronic pain. Synovial inflammation is correlated with OA progression and pain. Synovial inflammation can produce a series of destructive substances, such as inflammatory factors and pain mediators, which aggravate cartilage injury and further accelerate the progression of OA. Although many studies investigated the effects of synovial inflammation on the onset and progression of OA, there are limited reports regarding slowing the progression of OA and relieving pain by modulating synovial inflammation...

INTRODUCTION AND OBJECTIVE: The major sources of bacterial contamination of raw milk are post-harvest manipulation; therefore the disinfection of teat and teat cups which decrease the bacterial load has a positive impact on minimizing new infection rates. The aim of the study was determination of the incidence of pathogens on investigated surfaces, evaluation of the effectiveness of sanitation regime in the reduction of surface microbial load, and determination of the effectiveness of mechanical cleaning of teats in a milking parlour for dairy cows...

Cannabinoid CB2 receptor (CB2 R) agonists are investigated as therapeutic agents in the clinic. However, their molecular mode-of-action is not fully understood. Here, we report the discovery of LEI-102, a CB2 R agonist, used in conjunction with three other CBR ligands (APD371, HU308, and CP55,940) to investigate the selective CB2 R activation by binding kinetics, site-directed mutagenesis, and cryo-EM studies. We identify key residues for CB2 R activation. Highly lipophilic HU308 and the endocannabinoids, but not the more polar LEI-102, APD371, and CP55,940, reach the binding pocket through a membrane channel in TM1-TM7...

The experimental and theoretical study of influence of the conformational state and association on the chirality of the stereochemically nonrigid biologically active bis-camphorolidenpropylenediamine (CPDA) and its ability to induce the helical mesophase of alkoxycyanobiphenyls liquid-crystalline binary mixture was carried out. On the basis of quantum-chemical simulation of the CPDA structure, four relatively stable conformers were detected. A comparison of the calculated and experimental electronic circular dichroism (ECD) and 1 H, 13 C, 15 N NMR spectra, as well as specific optical rotation and dipole moments, allowed to establish the most probable trans-gauche conformational state (tg) of dicamphorodiimine and CPDA dimer with a predominantly mutually parallel arrangement of molecular dipoles...

3-3'-Diindolylmethane (DIM) is a biologically active dimer derived from the endogenous conversion of indole-3-carbinol (I3C), a naturally occurring glucosinolate found in many cruciferous vegetables (i.e., Brassicaceae ). DIM was the first pure androgen receptor antagonist isolated from the Brassicaceae family and has been recently investigated for its potential pharmacological use in prostate cancer prevention and treatment. Interestingly, there is evidence that DIM can also interact with cannabinoid receptors...

Pain, especially chronic pain, can strongly affect patients' quality of life. Cannabinoids ponhave been reported to produce potent analgesic effects in different preclinical pain models, where they primarily function as agonists of Gi/o protein-coupled cannabinoid CB1 and CB2 receptors. The CB1 receptors are abundantly expressed in both the peripheral and central nervous systems. The central activation of CB1 receptors is strongly associated with psychotropic adverse effects, thus largely limiting its therapeutic potential...

The alkylindole (AI), WIN55212-2, modulates the activity of several proteins, including cannabinoid receptors 1 and 2 (CB1 R, CB2 R), and at least additional G protein-coupled receptor (GPCR) that remains uncharacterized with respect to its molecular identity and pharmacological profile. Evidence suggests that such AI-sensitive GPCRs are expressed by the human kidney cell line HEK293. We synthesized fourteen novel AI analogues and evaluated their activities at AI-sensitive GPCRs using [35 S]GTPγS and [3 H]WIN55212-2 binding in HEK293 cell membranes, and performed in silico pharmacophore modeling to identify characteristics that favor binding to AI-sensitive GPCRs versus CB1 R/CB2 R...

Acute respiratory distress syndrome (ARDS) and sepsis are risk factors contributing to mortality in patients with pneumonia. In ARDS, also termed acute lung injury (ALI), pulmonary immune responses lead to excessive pro-inflammatory cytokine release and aberrant alveolar neutrophil infiltration. Systemic spread of cytokines is associated with systemic complications including sepsis, multi-organ failure, and death. Thus, dampening pro-inflammatory cytokine release is a viable strategy to improve outcome. Activation of cannabinoid type II receptor (CB2 ) has been shown to reduce cytokine release in various in vivo and in vitro studies...

3,3'-Diindolylmethane (DIM), a natural product-derived compound formed upon ingestion of cruciferous vegetables, was recently described to act as a partial agonist of the anti-inflammatory cannabinoid (CB) receptor subtype CB2 . In the present study, we synthesized and evaluated a series of DIM derivatives and determined their affinities for human CB receptor subtypes in radioligand binding studies. Potent compounds were additionally evaluated in functional cAMP accumulation and β-arrestin recruitment assays...

Microdialysis assays demonstrated a possible role of orexin in the regulation of amyloid beta peptide (Aß) levels in the hippocampal interstitial fluid in the APP transgenic model. CB2 R is overexpressed in activated microglia, showing a neuroprotective effect. These two receptors may interact, forming CB2 -OX1 -Hets and becoming a new target to combat Alzheimer's disease. Aims: Demonstrate the potential role of CB2 -OX1 -Hets expression and function in microglia from animal models of Alzheimer's disease. Receptor heteromer expression was detected by immunocytochemistry, bioluminescence resonance energy transfer (BRET) and proximity ligation assay (PLA) in transfected HEK-293T cells and microglia primary cultures...

Adolescence is a high-risk age for exposure to violent media (EVM) and bullying. Some previous theories and empirical studies have highlighted a moderated mediating model that normative beliefs about aggression (NBA) as a mediator and self-control (SC) as a moderator for the link between EVM and aggressive behaviors (including bullying behaviors). However, most previous studies analyzed traditional bullying (TB) and cyberbullying (CB) separately, which is not conducive to finding the differences between the two bullying behaviors...

Molecular dynamic (MD) simulations have become a common tool to study the pathway of ligand entry to the orthosteric binding site of G protein-coupled receptors. Here, we have combined MD simulations and site-directed mutagenesis to study the binding process of the potent JWH-133 agonist to the cannabinoid CB2 receptor (CB2 R). In CB2 R, the N-terminus and extracellular loop 2 fold over the ligand binding pocket, blocking access to the binding cavity from the extracellular environment. We, thus, hypothesized that the binding pathway is a multistage process consisting of the hydrophobic ligand diffusing in the lipid bilayer to contact a lipid-facing vestibule, from which the ligand enters an allosteric site inside the transmembrane bundle through a tunnel formed between TMs 1 and 7 and finally moving from the allosteric to the orthosteric binding cavity...