The CBI cannabinoid receptor has been shown to couple with pertussis toxin (PTX)-sensitive Gi/o proteins and inhibit adenylyl cyclase. However, in certain conditions, CBI mediates adenylyl cyclase activation, possibly through Gs-type G proteins. In rat BI03 neuroblastoma cells in which CBI gene was endogenously expressed, anandamide inhibited forskolin-induced cAMP accumulation via PTX-sensitive pathways. When CBI 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 CBI-over-expressing BI03 cells, anandamide induced cell rounding via a PTX-insensitive/Rho kinase inhibitor-sensitive pathway. These results suggest that the CBI receptor could couple with G proteins that activate Rho (possibly G12/13) as well as Gi/o and Gs.
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