Abstract
Pharmacological modulation of cannabinoid type 2 receptor
(CB2R) holds promise for the treatment of numerous conditions,
including inflammatory diseases, autoimmune disorders, pain, and cancer.
Despite the significance of this receptor, researchers lack reliable tools to
address questions concerning the expression and complex mechanism of CB2R
signaling, especially in cell-type and tissue-dependent context. Herein, we report
for the first time a versatile ligand platform for the modular design of a
collection of highly specific CB2R fluorescent probes, used successfully
across applications, species and cell types. These include flow
cytometry of endogenously expressing cells, real-time
confocal microscopy of mouse splenocytes and human macrophages, as well as FRET-based
kinetic and equilibrium binding assays. High CB2R specificity was
demonstrated by competition experiments in living cells expressing CB2R
at native levels. The probes were effectively applied to FACS analysis of
microglial cells derived from a mouse model relevant to Alzheimer’s disease and
to the detection of CB2R in human breast cancer cells.