Laguerre, Aurélien Hauke, Sebastian Qiu, Jian Kelly, Martin J. Schultz, Carsten Photorelease of 2‑Arachidonoylglycerol in Live Cells 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. CB 1-GIRK channel;CB 1-mediated inhibition;2- AG levels;2- AG;cannabinoid receptor 1;2-AG 2019-10-10
    https://acs.figshare.com/articles/journal_contribution/Photorelease_of_2_Arachidonoylglycerol_in_Live_Cells/9963698
10.1021/jacs.9b05978.s001