胍丁胺对阿片受体环腺苷—磷酸信号转导系统代偿适应的影响<英文>

Influence of agmatine in adaptation of cAMP signal transduction system of opiate receptors

目的:观察胍丁胺对阿片类所致脱敏和物质依赖的作用。方法:分别用放射配体结合实验和放免法测定γ-[^(35)S]-三磷鸟苷([^(35)S]GTTP)结合量和环腺苷一磷酸(cAMP)浓度。结果:在经阿片类药物预处理的NG108-15细胞实验中,胍丁胺使阿片类药物刺激[^(35)S]GTTP结合作用增强35％;使阿片类药物对cAMP抑制作用增强114.3％;使纳洛酮引起的吗啡物质依赖细胞cAMP超射幅度和对照组相比减小214.9％。胍丁胺的上述作用均可被咪唑克生浓度依赖性阻断。结论:胍丁胺通过激活咪唑啉受体阻止cAMP信号转导通路代偿适应过程的形成。

AIM: To observe attenuative effects of agmatine on opiate desensitization and substance dependence. METHODS: Guanosine 5'-O-(3-[35 S] thiotriphos-phate) ([35S]GTTP) binding and cellular cyclic AMP (cAMP) level were determined by radioligand binding assay and radioimmunoassay in NG108-15 cells, respectively. RESULTS: Agmatine increased stimulative action of opioids on [35S]GTTP binding by about 35 % and inhibitory effects of opioids on cellular cAMP concentration by about 114.3 % in NG108-15 cells pretreated with opioids. On the other hand, it also inhibited cAMP over-shooting by 214.9 % of morphine substance dependent cells precipitated by naloxone compared with that of control. These effects of agmatine were antagonized by idazoxan in a concentration-dependent manner. CONCLUSION: Agmatine reversed the formative process of adaptation in cAMP signal transduction cascade.