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Cannabinoid Receptor Ligand (cannabinoid + receptor_ligand)
Selected AbstractsCannabinoid receptor ligands as potential anticancer agents , high hopes for new therapies?JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2009Susanne Oesch Abstract Objectives The endocannabinoid system is an endogenous lipid signalling network comprising arachidonic-acid-derived ligands, cannabinoid (CB) receptors, transporters and endocannabinoid degrading enzymes. The CB1 receptor is predominantly expressed in neurons but is also co-expressed with the CB2 receptor in peripheral tissues. In recent years, CB receptor ligands, including ,9 -tetrahydrocannabinol, have been proposed as potential anticancer agents. Key findings This review critically discusses the pharmacology of CB receptor activation as a novel therapeutic anticancer strategy in terms of ligand selectivity, tissue specificity and potency. Intriguingly, antitumour effects mediated by cannabinoids are not confined to inhibition of cancer cell proliferation; cannabinoids also reduce angiogenesis, cell migration and metastasis, inhibit carcinogenesis and attenuate inflammatory processes. In the last decade several new selective CB1 and CB2 receptor agents have been described, but most studies in the area of cancer research have used non-selective CB ligands. Moreover, many of these ligands exert prominent CB receptor-independent pharmacological effects, such as activation of the G-protein-coupled receptor GPR55, peroxisome proliferator-activated receptor gamma and the transient receptor potential vanilloid channels. Summary The role of the endocannabinoid system in tumourigenesis is still poorly understood and the molecular mechanisms of cannabinoid anticancer action need to be elucidated. The development of CB2 -selective anticancer agents could be advantageous in light of the unwanted central effects exerted by CB1 receptor ligands. Probably the most interesting question is whether cannabinoids could be useful in chemoprevention or in combination with established chemotherapeutic agents. [source] Regioselective F-18 radiolabeling of AM694, a CB1 cannabinoid receptor ligandJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 9 2003Peter G. Willis Abstract [18F]AM694, [1-(5-[18F]fluoropentyl)-1H-indol-3-yl]-(2-iodophenyl)methanone, 1b, a potential radiotracer for imaging of cerebral cannabinoid receptor (CB1), has been synthesized by no-carrier-added regioselective radiofluorination of the corresponding tosylate. [18F]AM694 was obtained in 20% radiochemical yield (non-decay-corrected) with a specific activity of 14 500 mCi/µmol, a radiochemical purity of > 99%, and a chemical purity of 95.5%. Copyright © 2003 John Wiley & Sons, Ltd. [source] 2-Arachidonoylglycerol, an endogenous cannabinoid receptor ligand in the nervous tissueJOURNAL OF NEUROCHEMISTRY, Issue 2003K. Waku 2-Arachidonoylglycerol (2-AG) is a unique molecular species of monoacylglycerol identified as an endogenous cannabinoid receptor ligand by us and Mechoulam and co-workers (1). We found that 2-AG possesses binding activity toward the cannabinoid receptor in rat brain. We also found that 2-AG induces transient elevation of the intracellular Ca2+ concentration in NG108-15 cells. The response induced by 2-AG was blocked by pretreatment of cells with a cannabinoid CB1 receptor-specific antagonist SR141716A, indicating that CB1 receptor is involved in the response. Based on the results of structure,activity relationship experiments, we concluded that the cannabinoid CB1 receptor in the nervous system is originally and primary a 2-AG receptor. 2-AG was produced and released from nervous tissues following various types of stimulation through enhanced breakdown of arachidonic acid-containing phospholipids such as inositol phospholipids. Physiological and pathophysiological roles of 2-AG in the nervous system will be discussed. [source] Physiological roles of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligandBIOFACTORS, Issue 1 2009Takayuki Sugiura Abstract 2-Arachidonoylglycerol is an arachidonic acid-containing monoacylglycerol isolated from the rat brain and canine gut as an endogenous ligand for the cannabinoid receptors (CB1 and CB2). 2-Arachidonoylglycerol binds to both the CB1 receptor, abundantly expressed in the nervous system, and the CB2 receptor, mainly expressed in the immune system, with high affinity, and exhibits a variety of cannabimimetic activities. Notably, anandamide, another endogenous ligand for the cannabinoid receptors, acts as a partial agonist at these cannabinoid receptors, whereas 2-arachidonoylglycerol acts as a full agonist. The results of structure-activity relationship experiments strongly suggested that 2-arachidonoylglycerol rather than anandamide is the true natural ligand for both the CB1 and the CB2 receptors. Evidence is gradually accumulating which shows that 2-arachidonoylglycerol plays physiologically and pathophysiologically essential roles in various mammalian tissues and cells. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source] | ||||||||||