Journal ArticleDOI
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
TLDR
The cloning and expression of a complementary DNA that encodes a G protein-coupled receptor that is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana are suggested.Abstract:
Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS) in a complex and dose-dependent manner. Although CNS depression and analgesia are well documented effects of the cannabinoids, the mechanisms responsible for these and other cannabinoid-induced effects are not so far known. The hydrophobic nature of these substances has suggested that cannabinoids resemble anaesthetic agents in their action, that is, they nonspecifically disrupt cellular membranes. Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids. Here we report the cloning and expression of a complementary DNA that encodes a G protein-coupled receptor with all of these properties. Its messenger RNA is found in cell lines and regions of the brain that have cannabinoid receptors. These findings suggest that this protein is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana.read more
Citations
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Journal ArticleDOI
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
TL;DR: A comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy is provided.
Journal ArticleDOI
The molecular logic of endocannabinoid signalling
TL;DR: The endocannabinoids are a family of lipid messengers that engage the cell surface receptors that are targeted by Δ9-tetrahydrocannabinol, the active principle in marijuana (Cannabis).
Journal ArticleDOI
SR141716A, a potent and selective antagonist of the brain cannabinoid receptor
Murielle Rinaldi-Carmona,Francis Barth,Michel Heaulme,David Shire,Bernard Calandra,Christian Congy,Serge Martinez,Jeanne Maruani,Gervais Neliat,Daniel Caput,P. Ferrara,Philippe Soubrie,J. C. Breliere,Gérard Le Fur +13 more
TL;DR: SR141716A is the first selective and orally active antagonist of the brain cannabinoid receptor and should prove to be a powerful tool for investigating the in vivo functions of the anandamide/cannabinoid system.
Journal ArticleDOI
Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations.
Sylvaine Galiègue,Sophie Mary,Jean Marchand,Danielle Dussossoy,D. Carriere,Pierre Carayon,Monsif Bouaboula,David Shire,Gérard Le Fur,Pierre Casellas +9 more
TL;DR: The results suggest that CB1 and CB2 can be considered as tissue-selective antigens of the central nervous system and immune system, respectively, and cannabinoids may exert specific receptor-mediated actions on the immune system through the CB2 receptor.
Journal ArticleDOI
The endogenous cannabinoid system controls extinction of aversive memories
Giovanni Marsicano,Carsten T. Wotjak,Shahnaz Christina Azad,Shahnaz Christina Azad,Tiziana Bisogno,Gerhard Rammes,Maria Grazia Cascio,Heike Hermann,Jianrong Tang,Clementine Hofmann,Walter Zieglgänsberger,Vincenzo Di Marzo,Beat Lutz +12 more
TL;DR: Treatment of wild-type mice with the CB1 antagonist SR141716A mimicked the phenotype of CB1-deficient mice, revealing that CB1 is required at the moment of memory extinction, and proposes that endocannabinoids facilitate extinction of aversive memories through their selective inhibitory effects on local inhibitory networks in the amygdala.
References
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Journal ArticleDOI
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Journal ArticleDOI
Identification of a family of muscarinic acetylcholine receptor genes
TL;DR: Analysis of human and rat genomic clones indicates that there are at least four functional muscarinic receptor genes and that these genes lack introns in the coding sequence.