Journal ArticleDOI
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
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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
Isolation and structure of a brain constituent that binds to the cannabinoid receptor
William A. Devane,Lumir Hanus,Aviva Breuer,Roger G. Pertwee,Lesley A. Stevenson,Graeme Griffin,Dan Gibson,Asher Mandelbaum,A. Etinger,Raphael Mechoulam +9 more
TL;DR: In this article, an arachidonylethanthanolamide (anandamide) was identified in a screen for endogenous ligands for the cannabinoid receptor and its structure was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and confirmed by synthesis.
Journal ArticleDOI
Molecular characterization of a peripheral receptor for cannabinoids
TL;DR: The cloning of a receptor for cannabinoids is reported that is not expressed in the brain but rather in macrophages in the marginal zone of spleen, which helps clarify the non-psychoactive effects of cannabinoids.
Journal ArticleDOI
Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors.
Raphael Mechoulam,Shimon Ben-Shabat,Lumir Hanus,Moshe Ligumsky,Norbert E. Kaminski,Anthony R. Schatz,Asher Gopher,Shlomo Almog,Billy R. Martin,David R. Compton,Roger G. Pertwee,Graeme Griffin,Michael Bayewitch,Jacob Barg,Zvi Vogel +14 more
TL;DR: Upon intravenous administration to mice, 2-Ara-Gl caused the typical tetrad of effects produced by THC: antinociception, immobility, reduction of spontaneous activity, and lowering of the rectal temperature.
Journal ArticleDOI
International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors
Allyn C. Howlett,Francis Barth,Tom I. Bonner,Guy A. Cabral,Pierre Casellas,William A. Devane,Christian C. Felder,Miles Herkenham,Ken Mackie,Billy R. Martin,Raphael Mechoulam,Roger G. Pertwee +11 more
TL;DR: It is considered premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification, because pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging and other kinds of supporting evidence are still lacking.
Journal ArticleDOI
Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study
TL;DR: The results suggest that the presently characterized cannabinoid receptor mediates physiological and behavioral effects of natural and synthetic cannabinoids, because it is strongly coupled to guanine nucleotide regulatory proteins and is discretely localized to cortical, basal ganglia, and cerebellar structures involved with cognition and movement.
References
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Journal ArticleDOI
Lutropin-choriogonadotropin receptor: an unusual member of the G protein-coupled receptor family.
Keith C Mcfarland,Rolf Sprengel,Heidi S. Phillips,Martin Köhler,Nora Rosemblit,Karoly Nikolics,Deborah L. Segaloff,Peter H. Seeburg +7 more
TL;DR: The LH-CG-R gene may have evolved by recombination of LRG and G protein-coupled receptor genes and bind human choriogonadotropin with high affinity and show an increase in cyclic adenosine monophosphate when exposed to hormone.
Journal ArticleDOI
A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells.
Hiroto Okayama,Paul Berg +1 more
TL;DR: A plasmid vector for cloning cDNAs in Escherichia coli is described; the same vector also promotes expression of the cDNA segment in mammalian cells, and it is confirmed that the alpha-globin transcript produced in transfected cells is initiated correctly, spliced at either of the two introns, and polyadenylated either at the site coded in the c DNA segment or at the distal SV40polyadenylation signal.
Journal ArticleDOI
cDNA cloning of bovine substance-K receptor through oocyte expression system.
TL;DR: The result provides the first indication that the neuropeptide receptor has sequence similarity with rhodopsin-type receptors (the G-protein-coupled receptor family) and thus possesses multiple membrane-spanning domains.
Journal ArticleDOI
Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain
TL;DR: In situ hybridization histochemistry with synthetic oligodeoxyribonucleotide probes identified cells that synthesize mRNAs encoding tyrosine hydroxylase in the mesencephalon and substance P, enkephalin, and dynorphin in the rat forebrain.
Journal ArticleDOI
Cloning and sequencing of porcine LH-hCG receptor cDNA: variants lacking transmembrane domain.
Hugues Loosfelt,Micheline Misrahi,Michel Atger,Roland Salesse,Mai Tu Vu Hai-Luu Thi,André Jolivet,Anne Guiochon-Mantel,Sokhavuth Sar,Bahija Jallal,Jean Garnier,Edwin Milgrom +10 more
TL;DR: Hydropathy analysis suggests the existence of seven transmembrane domains that show homology with the corresponding regions of other G protein-coupled receptors.