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
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TLDR
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.Abstract:
Two types of cannabinoid receptor have been discovered so far, CB(1) (2.1: CBD:1:CB1:), cloned in 1990, and CB(2) (2.1:CBD:2:CB2:), cloned in 1993. Distinction between these receptors is based on differences in their predicted amino acid sequence, signaling mechanisms, tissue distribution, and sensitivity to certain potent agonists and antagonists that show marked selectivity for one or the other receptor type. Cannabinoid receptors CB(1) and CB(2) exhibit 48% amino acid sequence identity. Both receptor types are coupled through G proteins to adenylyl cyclase and mitogen-activated protein kinase. CB(1) receptors are also coupled through G proteins to several types of calcium and potassium channels. These receptors exist primarily on central and peripheral neurons, one of their functions being to inhibit neurotransmitter release. Indeed, endogenous CB(1) agonists probably serve as retrograde synaptic messengers. CB(2) receptors are present mainly on immune cells. Such cells also express CB(1) receptors, albeit to a lesser extent, with both receptor types exerting a broad spectrum of immune effects that includes modulation of cytokine release. Of several endogenous agonists for cannabinoid receptors identified thus far, the most notable are arachidonoylethanolamide, 2-arachidonoylglycerol, and 2-arachidonylglyceryl ether. It is unclear whether these eicosanoid molecules are the only, or primary, endogenous agonists. Hence, we consider it 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. Although pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging, other kinds of supporting evidence are still lacking.read more
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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
Role of Endogenous Cannabinoids in Synaptic Signaling
TL;DR: The synthetic pathways of endocannabinoids are discussed, along with the putative mechanisms of their release, uptake, and degradation, and the fine-grain anatomical distribution of the neuronal cannabinoid receptor CB1 is described in most brain areas, emphasizing its general presynaptic localization and role in controlling neurotransmitter release.
Journal ArticleDOI
The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin
TL;DR: This review focuses on the manner with which three of these compounds, (−)‐trans‐Δ 9‐tetrahydrocannabinol (Δ9‐THC), (−]‐cannabidiol (CBD) and (−)-trans‐ Δ9‐TetrahYDrocannabivarin (Γ‐THCV), interact with cannabinoid CB1 and CB2 receptors.
Journal ArticleDOI
Identification and Functional Characterization of Brainstem Cannabinoid CB2 Receptors
Marja D. Van Sickle,Marnie Duncan,Philip J. Kingsley,Abdeslam Mouihate,Paolo Urbani,Ken Mackie,Nephi Stella,Alexandros Makriyannis,Daniele Piomelli,Joseph S. Davison,Lawrence J. Marnett,Vincenzo Di Marzo,Quentin J. Pittman,Kamala D. Patel,Keith A. Sharkey +14 more
TL;DR: These functional CB2 receptors in the brainstem were activated by a CB2 receptor agonist, 2-arachidonoylglycerol, and by elevated endogenous levels of endocannabinoids, which also act at CB1 receptors.
Journal ArticleDOI
International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB1 and CB2
Roger G. Pertwee,Allyn C. Howlett,Mary E. Abood,Stephen P.H. Alexander,V. Di Marzo,Maurice R. Elphick,Peter J. Greasley,Harald S. Hansen,George Kunos,Ken Mackie,Raphael Mechoulam,Ruth Alexandra Ross +11 more
TL;DR: This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non- CB1, non-CB2 established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors.
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
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Journal ArticleDOI
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
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Journal ArticleDOI
Molecular characterization of a peripheral receptor for cannabinoids
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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 Article
Determination and characterization of a cannabinoid receptor in rat brain.
TL;DR: The criteria for a high affinity, stereoselective, pharmacologically distinct cannabinoid receptor in brain tissue have been fulfilled.