Figure 6.

S426A/S430A mutants are more sensitive to endocannabinoids. A, B, S426A/S430A mutants (red bars or lines with circles) exhibit increased antinociceptive (A) and hypothermic (B) responses to 50 mg/kg AEA that was administered 30 min after 10 mg/kg URB597 compared with WT mice (black bars or lines with squares). C, D, The dose–response curves for the antinociceptive (C) and hypothermic (D) effects of 10 mg/kg URB597 combined with 1, 3, 10, or 30 mg/kg AEA were shifted to the left in the S426A/S430A mutant mice. E, F, The dose–response curves for the antinociceptive (E) and hypothermic (F) effects of the dual FAAH and MAGL inhibitor JZL195 were also shifted to the left for S426A/S430A mutant mice. Error bars represent the SEM and data analyses were performed using unpaired Student's t test (A) and two-way ANOVA with Bonferroni post hoc tests (B–F). *p < 0.05, **p < 0.01, ****p < 0.0001. Sample sizes for each group are in parentheses.