Anandamide-induced neuroblastoma cell rounding via the CB1 cannabinoid receptors.
The CB1 cannabinoid receptor has been shown to couple with pertussis toxin (PTX)-sensitive Gi/o proteins and inhibit adenylyl cyclase. However, in certain conditions, CB1 mediates adenylyl cyclase activation, possibly through Gs-type G proteins. In rat B103 neuroblastoma cells in which CBI gene was endogenously expressed, anandamide inhibited forskolin-induced cAMP accumulation via PTX-sensitive pathways. When CB1 was heterologously over-expressed using a retroviral transfer, high concentrations of anandamide increased forskolin-induced cAMP accumulation, and this effect was more prominent when cells were pretreated with PTX. In CB1-over-expressing B103 cells, anandamide induced cell rounding via a PTX-insensitive/Rho kinase inhibitor-sensitive pathway. These results suggest that the CB1 receptor could couple with G proteins that activate Rho (possibly G12/13) as well as Gi/o and Gs.
Ishii
Isao
I
Department of Molecular Genetics, National Institute of Neuroscience, NCNP, Ogawahigashi 4-1-1, Kodaira, Tokyo 187-8502, Japan.
Chun
Jerold
J
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002186:Cannabinoids / Q000378:metabolism*; D048429:Cell Size / Q000187:drug effects; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D051379:Mice; D008810:Mice, Inbred C57BL; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D053284:Polyunsaturated Alkamides; D051381:Rats; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000242:Cyclic AMP; C078814:anandamide