Photorelease of 2-Arachidonoylglycerol in Live Cells

Aurélien Laguerre, Sebastian Hauke, Jian Qiu, Martin J. Kelly, Carsten Schultz

Research output: Contribution to journalArticle

Abstract

2-Arachidonoylglycerol (2-AG) is acting as a full agonist of cannabinoid receptor 1 and 2. Direct manipulation of 2-AG levels is a challenging task. The amphiphilic properties and the instability of 2-AG in aqueous media complicate its use as a drug-like molecule. Additionally, inhibition of the protein machinery that regulates 2-AG levels may also affect other monoacylglycerols. Therefore, we developed a novel method to elevate 2-AG levels with a flash of light. The resulting tool is a photoactivatable "caged" 2-arachidonoylglycerol (cg2-AG) allowing for the rapid photorelease of the signaling lipid in live cells. We characterized the mechanism of uncaging and the effect of 2-AG on the regulation of the β-cell signaling network. After uncaging of 2-AG, we monitored calcium levels, CB1-GIRK channel coupling, and CB1-mediated inhibition of adenylate cyclase and protein kinase A activity.

Original languageEnglish (US)
Pages (from-to)16544-16547
Number of pages4
JournalJournal of the American Chemical Society
Volume141
Issue number42
DOIs
StatePublished - Oct 23 2019

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ASJC Scopus subject areas

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

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