Cannabinoids enhance human B-cell growth at low nanomolar concentrations.
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.
Derocq
J M
JM
Department of Immunology, Sanofi Recherche, Montpellier, France.
Ségui
M
M
Marchand
J
J
Le Fur
G
G
Casellas
P
P
D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D001483:Base Sequence; D048588:Benzoxazines; D019013:CD40 Antigens; D002186:Cannabinoids / Q000138:chemical synthesis / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003511:Cyclohexanols / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D013759:Dronabinol / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D014066:Palatine Tonsil; D037342:Pertussis Toxin; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077285:Rimonabant; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D048588:Benzoxazines; D019013:CD40 Antigens; D002186:Cannabinoids; D003511:Cyclohexanols; D008024:Ligands; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D010566:Virulence Factors, Bordetella; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D004247:DNA; D037342:Pertussis Toxin; D000077285:Rimonabant