ja9b05978_si_001.pdf (1.49 MB)
Photorelease of 2‑Arachidonoylglycerol in Live Cells
journal contribution
posted on 2019-10-10, 13:37 authored by Aurélien Laguerre, Sebastian Hauke, Jian Qiu, Martin J. Kelly, Carsten Schultz2-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.