Journal ArticleDOI
Molecular characterization of a peripheral receptor for cannabinoids
TLDR
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.Abstract:
THE major active ingredient of marijuana, Δ9-tetrahydrocannabi-nol (Δ9-THC), has been used as a psychoactive agent for thousands of years. Marijuana, and Δ9-THC, also exert a wide range of other effects including analgesia, anti-inflammation, immunosuppression, anticonvulsion, alleviation of intraocular pressure in glaucoma, and attenuation of vomiting1. The clinical application of cannabinoids has, however, been limited by their psychoactive effects, and this has led to interest in the biochemical bases of their action. Progress stemmed initially from the synthesis of potent derivatives of δ9-THC4,5, and more recently from the cloning of a gene encoding a G-protein-coupled receptor for cannabinoids6. This receptor is expressed in the brain but not in the periphery, except for a low level in testes. It has been proposed that the non-psychoactive effects of cannabinoids are either mediated centrally or through direct interaction with other, non-receptor proteins1,7,8. Here we report the cloning of a receptor for cannabinoids that is not expressed in the brain but rather in macrophages in the marginal zone of spleen.read more
Citations
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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
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.
References
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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
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
TL;DR: 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.
Journal ArticleDOI
Cannabinoid receptor localization in brain
TL;DR: The potencies of a series of natural and synthetic cannabinoids as competitors of [3H]CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in the in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience.
Journal ArticleDOI
The HL-60 promyelocytic leukemia cell line: proliferation, differentiation, and cellular oncogene expression
TL;DR: The HL-60 cell line, derived from a single patient with acute promyelocytic leukemia, provides a unique in vitro model system for studying the cellular and molecular events involved in the proliferation and differentiation of normal and leukemic cells of the granulocyte/monocyte/macrophage lineage.
Journal ArticleDOI
The probable arrangement of the helices in G protein-coupled receptors.
TL;DR: The structural constraints for the receptors are used to allocate particular helices to the peaks in the recently published projection map of rhodopsin and to propose a tentative three‐dimensional arrangement of the helices in G protein‐coupled receptors.