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Genetically Encoded CB2R-Based Fluorescent Sensor Enables Rapid Screening and Functional Assessment of Cannabinoid
Pinaki Bhattacharjee1, Paul D Volesky1, Samay Shivshankar1
1Section on Medicinal Chemistry, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Rockville, MD 20852, USA.
None:
The G-protein-coupled receptor cannabinoid receptor 2 (CB2R) initiates a key signaling pathway in mammalian physiology and pathophysiology. CB2R signaling holds significant therapeutic potential in ameliorating many pathologies, particularly in inflammatory conditions, neurodegenerative disorders, fibroproliferative and ocular diseases. CB2 modulators have been studied for their anti-inflammatory and tissue protective effects in preclinical animal models of cardiovascular, gastrointestinal, liver, kidney, lung and neurodegenerative disorders with numerous compounds undergoing clinical evaluation. Existing ligands can be classified as endocannabinoids, cannabinoid-like natural products and synthetic CB2R ligands. A genetically encoded G-protein-coupled receptor activation-based (GRAB) sensor for CB1R-GRABeCB2.0 was developed recently. This current study extends the sensor's development to allow for a GPCR activation-based sensor for CB2R. The sensor, GRAB-CB2, will facilitate the evaluation of pharmacological characteristics and responses of various functionally selective and indiscriminate cannabinoid ligands acting on CB2.
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