论文部分内容阅读
Cannabinoid and nicotinic acetylcholine receptors are strongly associated with algesia. Previous studies in our laboratory have reported inhibitory effects of synthetic cannabinoid WIN55, 212-2 on nicotine-activated currents (/nic), but the underlying mechanisms remain poorly understood. The present study used whole-cell patch clamp techniques to investigate the modulatory effects of synthetic cannabinoid WIN55, 212-2 on /nic in cultured rat trigeminal ganglion neurons. The results revealed several major findings: WIN55, 212-2 inhibited /nic in rat trigeminal ganglion neurons. In addition, when WIN55, 212-2 (3 μmol/L) was applied simultaneously with nicotine (100 μmol/L), the inhibition of WIN55, 212-2 on /nic was reversible, concentration-dependent and voltage-independent. This effect was not mediated by CB1, CB2 or VR1 receptors; neither the selective CB1 receptor antagonist AM281, CB2 receptor antagonist AM630 nor VR1 receptor antagonist capsazepine reduced the inhibitory effect of WIN55, 212-2. Further, the inhibition of nicotinic responses by WIN55, 212-2 was not sensitive to the membrane permeable cyclic adenosine monophosphate (cAMP) analog 8-Br-cAMP. The G-protein inhibitor GDP-β-S (1 mmol/L) did not block the inhibitory effects of WIN55, 212-2 on /nic, excluding the involvement of G-protein mediation. The results suggested that WIN55, 212-2 inhibits/nic directly via the neuronal nicotinic acetylcholine receptor, and that this inhibition is non-competitive. WIN55, 212-2 did not act as an open channel blocker of the neuronal nicotinic acetylcholine receptor, and did not affect the desensitization of /nic. The results suggest that nicotine receptors may be physically plugged from outside the membrane by drugs containing WIN55, 212-2.