BACKGROUND AND PURPOSE A nonpsychoactive constituent of the cannabis plant, cannabidiol has been demonstrated to have low affinity for both cannabinoid CB1 and CB2 receptors. We have shown previously that cannabidiol can enhance electrically evoked contractions of the mouse vas deferens, suggestive of inverse agonism. We have also shown that cannabidiol can antagonize cannabinoid receptor agoni...

Troponin-T was cleaved by cyanogen bromide (CB) to produce the seven fragments CB1 (151 residues), CB3 (70 residues), CB2 (81 residues), CB5 (24 residues), CB4 (54 residues), CB7 (8 residues), and CB6 (21 residues). The NH2-terminal fragment CB1, composed of CB3 plus CB2, had an internal homoserine which was not completely cleaved. The amino acid sequence of CB2 was determined by a combination ...

Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, United Kingdom (N.N., D.R., M.P.S., G.P.M., T.J.S., T.P.J.D., K.S.L., P.D.); Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom (S.M.); and Cambridge Centre for Proteomics, Cambridge Systems Biology Centre, Department of Biochemistry, University of Cambridge, Cambridge CB2 1QR, Unite...

The potential for therapeutic specificity in regulating diseases has made cannabinoid (CB) receptors one of the most important G-protein-coupled receptor (GPCR) targets in search for new drugs. Considering the lack of related 3D experimental structures, we have established a structure-based virtual screening protocol to search for CB2 bioactive antagonists based on the 3D CB2 homology structure...

Several studies have indicated that the cannabinoid receptor 2 (CB2) plays an important role in neuroinflammation associated with Alzheimer's disease (AD) progression. The present study examined the role of CB2 in microglia activation in vitro as well as characterizing the neuroinflammatory process in a transgenic mouse model of AD (APP/PS1 mice). We demonstrate that microglia harvested from CB...

During parenchymal brain metastasis formation tumor cells need to migrate through cerebral endothelial cells, which form the morphological basis of the blood-brain barrier (BBB). The mechanisms of extravasation of tumor cells are highly uncharacterized, but in some aspects recapitulate the diapedesis of leukocytes. Extravasation of leukocytes through the BBB is decreased by the activation of ty...

We designed AM1241, a selective CB2 cannabinoid receptor agonist, and used it to test the hypothesis that CB2 receptor activation would reverse the sensory hypersensitivity observed in neuropathic pain states. AM1241 exhibits high affinity and selectivity for CB2 receptors. It also exhibits high potency in vivo. AM1241 dose-dependently reversed tactile and thermal hypersensitivity produced by l...

BACKGROUND Cannabinoid (CB) receptors may be involved in the control of bladder function; the role of CB receptor subtypes in micturition has not been established. OBJECTIVES Our aim was to evaluate the effects of cannabinor, a novel CB2 receptor agonist, on rat bladder function. DESIGN, SETTING, AND PARTICIPANTS Sprague Dawley rats were used. Distribution of CB2 receptors in sensory and ch...

A series of quinolinyl and isoquinolinyl phenyl ketones was synthesized and their CB2 receptor-dependent G-protein activities were determined using the [S]GTPcS binding assay. Both quinoline and isoquinoline derivatives exhibited similar CB2 receptor agonist activity, the most potent ligands being the 2-(Me2N)-phenyl substituted derivatives, which were also full agonists at the CB2-receptor. 20...

In the present report, we investigated in detail the effects of SR 144528, a selective antagonist of the peripheral cannabinoid receptor (CB2), on two well-characterized functions mediated by CB2: the induction of the early response gene krox24 and the inhibition of adenylyl cyclase. We generated Chinese hamster ovary cells doubly transfected with human CB2 and a luciferase reporter gene linked...