Fig. 2

Competitive gel-based ABPP reveals high FAAH over MAGL activity in human dura mater. A Human dura mater was pre-incubated for 1 h with DMSO (vehicle), MAGL-inhibitors JJKK-048 (100 nM) and KML-29 (1 μM) and FAAH-inhibitors JZP-327A (1 μM) and JZP-430 (1 μM), and then labelled with fluorescent probe TAMRA-FP, as indicated in the Methods. TAMRA-FP-labelled bands appear dark after in-gel imaging. FAAH and MAGL were identified based on selective inhibition and their expected molecular weights. MAGL and FAAH band-intensities after DMSO treatment represent basal MAGL and FAAH activities, respectively. Note that FAAH activity after DMSO treatment is high whereas basal MAGL activity is practically absent. Basal FAAH- activity appears reduced with JZP-327A and with JZP-430. MAGL-inhibitor, JJKK-048 (100 nM), decreased FAAH basal activity as off-target. B Statistics comparing the basal activity of MAGL and FAAH in human meninges. FAAH basal activity (DMSO) was found higher than MAGL activity (N = 6, Mann Whitney U test, * = 0.033). C LC–MS/MS data comparing AEA and 2-AG levels in naïve human meninges. The level of 2-AG was much higher than that of AEA (N = 6, Mann Whitney U test, ** = 0.002)