论文部分内容阅读
目的 研究吗啡耐受和依赖时某些第二信使分子和阿片受体变化及与谷氨酸受体的关系。方法 竞争性蛋白结合法、共聚焦显微镜技术和受体结合实验检测 c AMP水平、胞内钙和阿片受体变化。结果 在表达诱导型一氧化氮合酶 c DNA神经细胞中 ,吗啡急性刺激剂量依赖性抑制 c AMP生成 ,慢性用药引起 c AMP代偿性增加。谷氨酸受体拮抗剂 MK80 1增强吗啡的急性抑制效应 ,抑制阿片受体介导 c AMP系统脱敏。对吗啡慢性给药细胞 ,用吗啡刺激和纳络酮戒断引起 [Ca2 + ]i增加 ,阿片受体 Kd值增加和 Bmax值减少 ,MK80 1对这些指标的改变没有影响。结论 MK80 1减轻阿片耐受和依赖的机制可能不是改变阿片受体特性 ,主要与受体后信号转导有关。
Objective To investigate the changes of some second messenger molecules and opioid receptors in morphine tolerance and dependence and its relationship with glutamate receptors. Methods Competitive protein binding assay, confocal microscopy and receptor binding assay were used to detect the levels of c AMP, intracellular calcium and opioid receptors. Results In the expression of inducible nitric oxide synthase c DNA neurons, acute morphine stimulation dose-dependently inhibited the production of cAMP, chronic medication induced cAMP compensatory increase. Glutamate receptor antagonist MK80 1 enhances the acute inhibitory effect of morphine and inhibits opiate receptor-mediated cAMP system desensitization. For chronic administration of morphine, the increase of [Ca2 +] i, the increase of Kd and the decrease of Bmax of opioid receptors were induced by morphine stimulation and naloxone withdrawal. MK80 1 had no effect on the changes of these indexes. Conclusion The mechanism by which MK80 1 can reduce the opioid tolerance and dependence may not change the opioid receptor characteristics, which is mainly related to post-receptor signal transduction.