Abstract
This study examined the effect of cannabinoid ligands on human tonsillar B-cells activated either through cross-linking of surface immunoglobulins or ligation of the CD40 antigen. The two synthetic cannabinoids, CP55,940 and WIN55212-2, as well as delta 9-tetrahydrocannabinol (THC), the psychoactive component of marijuana, caused a dose-dependent increase of B-cell proliferation and displayed EC50 at low nanomolar concentrations. This cannabinoid-induced enhancing activity was inhibited by pertussis toxin which suggested a G-protein-coupled receptor process. In addition, the absence of antagonistic effect of SR141716A, a specific CB1 receptor antagonist, together with the demonstration that human B-cells displayed large amount of CB2 receptor mRNAs, led us to assume that the growth enhancing activity observed on B-cells at very low concentrations of cannabinoids could be mediated through the CB2 receptor.
MeSH terms
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Antigens, CD / metabolism
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Antigens, Differentiation, B-Lymphocyte / metabolism
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B-Lymphocytes / cytology
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B-Lymphocytes / drug effects*
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Base Sequence
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Benzoxazines
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CD40 Antigens
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Cannabinoids / chemical synthesis
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Cannabinoids / pharmacology*
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Cell Division / drug effects
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Cyclohexanols / pharmacology*
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DNA / biosynthesis
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Dronabinol / pharmacology*
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Humans
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Ligands
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Lymphocyte Activation
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Molecular Sequence Data
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Morpholines / pharmacology*
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Naphthalenes / pharmacology*
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Palatine Tonsil
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Pertussis Toxin
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Piperidines / pharmacology
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Pyrazoles / pharmacology
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RNA, Messenger / analysis
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Receptors, Antigen, B-Cell / metabolism
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Receptors, Cannabinoid
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Receptors, Drug / antagonists & inhibitors
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Receptors, Drug / physiology*
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Rimonabant
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Virulence Factors, Bordetella / pharmacology
Substances
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Antigens, CD
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Antigens, Differentiation, B-Lymphocyte
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Benzoxazines
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CD40 Antigens
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Cannabinoids
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Cyclohexanols
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Ligands
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Morpholines
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Naphthalenes
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Piperidines
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Pyrazoles
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RNA, Messenger
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Receptors, Antigen, B-Cell
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Receptors, Cannabinoid
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Receptors, Drug
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Virulence Factors, Bordetella
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(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
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Dronabinol
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3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
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DNA
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Pertussis Toxin
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Rimonabant