Optical Control of Cannabinoid Receptor 2-Mediated Ca²⁺ Release Enabled by Synthesis of Photoswitchable Probes

Cannabinoid receptor 2 (CB2) is a promising target for the treatment of neuroinflammation and other diseases. However, lack understanding its complex signaling in cells tissues complicates therapeutic exploitation CB2 as drug target. We show first time that benchmark agonist HU308 increases cytosolic Ca2+ levels AtT-20(CB2) via phospholipase C. The synthesis photoswitchable derivatives from common building block 3-OTf-HU308 enables optical control over this pathway with spatiotemporal precision, demonstrated real-time fluorescence assay. Our findings reveal novel messenger by which affect cellular excitability, they demonstrate utility chemical photoswitches to monitor