Potentiation of adenosine A₁ receptor agonist CPA-induced antinociception by paeoniflorin in mice

The effect of paeoniflorin (PF), a major constituent isolated from Paeony radix, on N⁶-Cyclopentyladenosine (CPA), a selective adenosine A ₁ receptor (A₁ receptor) agonist, induced antinociception was examined in mice. In the tail-pressure test, CPA (0.05, 0.1, 0.2 mg/kg, s.c.) could induce antinociception in a dose-dependent manner. PF (5, 10, 20 mg/kg, s.c.) alone failed to exhibit any antinociceptive effect in mice; however, pretreatment of PF (20 mg/kg, s.c.) could significantly enhance CPA-induced antinociception. Additionally, pretreatment of 8-Cyclopentyl-1,3- dipropylxanthine (DPCPX, 0.25 mg/kg, s.c.), a selective A₁ receptor antagonist, could antagonize the antinociceptive effect of combining CPA with PF. Furthermore, in the competitive binding experiments, PF did not displace the binding of [³H]-8-Cyclopentyl-1,3-dipropylxanthine ([ ³H]-DPCPX) but displaced that of [³H]-2-Chloro-N ⁶-cyclopentyladenosine ([³H]-CCPA, a selective A ₁ receptor agonist) to the membrane preparation of rat cerebral cortex. These results suggested that PF might selectively increase the binding and antinociceptive effect of CPA by binding with A₁ receptor.