FIGURE 4.

Cellular and extracellular AEA levels measured by GC/MS in the presence of FAAH inhibitors alone or in combination with UCM707 or OMDM-2. A, intracellular AEA level measured after a 5-min incubation of 100 nm AEA and 20-min pretreatment with 100 nm URB597 alone and in the presence of 1 μm UCM707 or 5 μm OMDM-2 in U937 cells (10⁶ cells). B, the same experiments were carried out in the presence of 1 μm PMSF. In both cases, the intracellular accumulation of AEA induced by URB597 and PMSF was completely abolished in the presence of an EMT inhibitor. In the same experimental conditions, the extracellular AEA accumulation was measured after pretreatment with URB597 alone and in the presence of 1 μm UCM707 or 5 μm OMDM-2 (C) or with PMSF alone and in combination (D). The values are expressed as a percentage of cellular or extracellular AEA level as compared with vehicle-treated control. Data show mean values ± S.E. (error bars) of three independent experiments, each one carried out at least in triplicate. *, p < 0.05; **, p < 0.01, treated versus vehicle-treated control. #, p < 0.05; ##, p < 0.01, combination treatment versus URB597 or PMSF alone.