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J Am Chem Soc ; 142(40): 16953-16964, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-32902974

RESUMO

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 contexts. 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.


Assuntos
Doença de Alzheimer/metabolismo , Corantes Fluorescentes/química , Microglia/metabolismo , Receptor CB2 de Canabinoide/análise , Animais , Células CHO , Cricetulus , Modelos Animais de Doenças , Citometria de Fluxo , Transferência Ressonante de Energia de Fluorescência , Humanos , Ligantes , Camundongos , Simulação de Acoplamento Molecular , Sondas Moleculares/química , Imagem Óptica , Sensibilidade e Especificidade , Transdução de Sinais
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