Figure 2

The A ₁ R dependent thermal antinociceptive effect of AMP, when combined with nucleoside transport inhibitors, is reduced in Pap^-/- , Nt5e^-/- , and dKO mice. (A) AMP is hydrolyzed to adenosine by PAP and NT5E. Since adenosine is rapidly metabolized and transported into cells, we found it was necessary to block the reuptake of adenosine with nucleoside transport (ENT) inhibitors (like ITU or DIP). This allowed us to detect antinociceptive effects of adenosine under experimental conditions (behavior, field recordings). (B) Noxious thermal sensitivity was measured before (baseline, BL) and after i.t. injection of AMP (200 nmol)+DIP (5 nmol). These drugs have no antinociceptive effects when injected individually at these concentrations (not shown). A repeated measures two-way ANOVA was performed to compare all data sets (P < 0.0005 for WT, Pap^-/- and Nt5e^-/-), and Bonferroni's post-hoc tests were performed to compare each genotype to baseline values at each time point. (n = 8 mice per genotype). (C) Noxious thermal sensitivity was measured before (BL) and after i.t. injection of AMP (200 nmol)+ITU (5 nmol). These drugs have no antinociceptive effects when injected individually at these concentrations [10]. A repeated measures two-way ANOVA was performed to compare data sets (P < 0.0005 for WT, Pap^-/-, and Nt5e^-/-), and Bonferroni's post hoc-tests were performed to compare each genotype to baseline at each time point. (n = 9-10 mice per genotype). A ₁ R^-/- data in (C) replotted from [10]. (C-E) All data are presented as means ± s.e.m. *P < 0.05, **P < 0.005, ***P < 0.0005.