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

Roman C. Sarott, Alexander E.G. Viray, Patrick Pfaff, Anastasiia Sadybekov, Gabriela Rajic, Vsevolod Katritch, Erick M. Carreira, James A. Frank

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)736-743
Number of pages8
JournalJournal of the American Chemical Society
Volume143
Issue number2
DOIs
StatePublished - Jan 20 2021

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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