CCK－8可对抗μ－阿片受体介导的对大鼠背根节神经元钙通道的抑制效应

CHOLECYSTOKININ OCTAPEPTIDE REVERSES μ-OPIOID-RECEPTOR-MEDIATED INHIBITION OF CALCIUM CURRENT IN RAT DORSAL ROOT GANGLION NEURONS

ＣＣＫ－８在脊髓水平可对抗μ－阿片受体介导的抗伤害性作用，但其作用位，点及机制尚不清楚。本实验以急性分离的大鼠背根节（ＤＲＧ）神经元为标本，用全细胞膜片钳（ｗｈｏｌｅ－ｃｅｌｌｐａｔｃｈ－ｃｌａｍｐ）方法记录钙通道电流，观察分析特异性μ－受体激动剂羟甲芬太尼（ＯＭＦ）对电压依赖性钙通道电流的作用，以及在同一细胞上ＣＣＫ－８对此作用的影响。结果显示ＯＭＦ可明显抑制钙通道电流，其抑制作用可被μ－受体拮抗剂纳络酮或ＣＣＫ－８所翻转，而ＣＣＫ－８的作用又可被ＣＣＫ－Ｂ受体拮抗剂Ｌ３６５，２６０所对抗。结果提示：ＣＣＫ－８可在同一细胞上经ＣＣＫ－Ｂ受体对抗阿片效应。ＣＣＫ－８本身对钙通道电流并无增强效应，相反它可引起抑制作用。关于ＣＣＫ－８如何对抗μ－受体介导的机制有待进一步研究。

Cholecystokinin octapeptide(CCK-8)has been reported to antagonize the analgesic effect produced by μ-opioid agonist in spinal cord.However their mechanism and sites of action remain obscure. In the present study,whole-cell patch-clamp recording was performed on acutely isolated rat dorsal root ganglion(DRG) neurons to evaluate the effects of the specific μ-opioid agonist ohmefentanyl(OMF)on voltage gated calcium channels and the possible interaction between CCK-8 and OMF. The results indicated that OMF can depress the calcium currents of DRG neurons, and the depression of OMF can be readily reversed by μ-opioid receptor antagonist naloxone or by the antiopioid peptide CCK-8.Furthermore,the effect of CCK-8 can be abolished by CCK-B receptor antagonist L365,260.CCK-8 per se has no enhancing effect, rather a depressant effect,on calcium currents.We conclude that the depressant effect produced by μ-opioid on voltagegated calcium current in DRG neuron can be antagonized by CCK-8 through CCK-B receptor in the same neuron.