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1992年克隆出阿片δ受体后,已从不同种属的动物克隆出了阿片受体的三个亚型μ、δ和k受体。最近法国Kieffer实验室的Matthes等利用小鼠胚胎干细胞基因敲出技术繁育成功了一个μ阿片受体缺陷的种系小鼠。这种小鼠除无出阿片受体外,生长、发育、生殖和活动周期等与正常小鼠无异,且小鼠的δ和k受体的数量和分布、内源性阿片肽的表达和对热刺激的敏感性都与正常小鼠无异。给予该小鼠吗啡,无镇痛、位置偏爱和身体依赖性作用,给予纳洛酮也不出现撤药综合征。给予δ受体的选择性激动剂也无镇痛作用。说明吗啡的镇痛、位置偏爱和身体依赖性作用由μ受体介导,而与δ和k受体无关。
After the 1992 opioid δ receptor was cloned, three subtypes of μ, δ and k receptors of opioid receptors have been cloned from animals of different species. Recently, Matthes et al. At Kieffer Laboratory in France used mouse embryonic stem cell gene knock-out technology to breed a germ-line mouse that succeeded in a mu opioid receptor deficiency. In addition to being free of opiate receptors, this mouse is similar to normal mice in growth, development, reproduction, and activity cycle, and the number and distribution of δ and k receptors in mice, the expression of endogenous opioid peptides and Sensitivity to heat stimulation is no different from normal mice. Morphine was given to the mice without analgesic, place preference and body-dependent effects and no withdrawal syndrome was observed with naloxone. Selective agonists at the δ receptor also have no analgesic effect. Indicating morphine analgesia, place preference and body-dependent effects mediated by mu receptors, but not with delta and k receptors.