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 N-6-Cyclopentyladenosine (CPA), a selective adenosine A(1) receptor (A(1) 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 PIT (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 A, 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 [H-3]-8-Cyclopentyl-1,3-dipropylxanthine ([3 HI-DPCPX) but displaced that of [H-3]-2-Chloro-N-6-cyclopentyladenosine ([H-3]-CCPA, a selective A, 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 A, receptor.