LPK-26对κ阿片受体的调节作用及其作用机制的研究

目的:从细胞水平探讨LPK-26对κ受体的作用及分子机制。方法:通过3H]-Dip和35S]GTPγS放射性结合实验研究LPK-26对CHO细胞上稳定表达κ阿片受体的竞争性受体结合特征及LPK-26对κ阿片受体偶联的G蛋白的激活。结果:LPK-26是一种κ阿片受体激动剂,其Ki值是0.66 nmol.L-1,与U50,488H相似;并且通过35S]GTPγS结合实验,LPK-26激活G蛋白的能力明显大于U50,488H。结论:LPK-26可能是一种较为理想的新型镇痛药物。

STUDIES ON REGULATORY EFFECTS AND MECHANISMS OF LPK-26 ON KAPPA OPIOID RECEPTORS

Objective: To demonstrate the molecular mechanism of LPK-26 on the regulation of κ opioid receptor.Methods:\Diprenorphine binding assay was used to explore the characterization of LPK-26 in cloned human κ opioid receptors stably expressed in Chinese Hamster Ovary cells(CHO/κOR)by saturation binding experiments and competition binding experiments.Additionally,the activation of G protein by LPK-26 was determined by \GTPγS binding.Results:In this study,we demonstrated that LPK-26 display a high affinity for κ-opioid receptors with Ki value of 0.66 nmol·L-1.Although the Ki value of LPK-26 is similar to that of U50,488H,LPK-26 exhibited a greater ability to stimulate \GTPγS binding to membranes than U50,488H.Conclusion:The study suggested that LPK-26 might be promising candidates for the development of a safer analgesic.