Barg J, Belcheva M, Rowinski J, Ho A, Burke W J, Chung H D, Schmidt C A, Coscia C J
Department of Biochemistry and Molecular Biology, St. Louis University, MO 63104-1079.
Brain Res. 1993 Dec 31;632(1-2):209-15. doi: 10.1016/0006-8993(93)91155-l.
Since opioids can influence the release of acetylcholine, substance P and a number of other neurotransmitters that have been implicated in the pathogenesis of Alzheimer's disease (AD), it is of interest to assess opioid receptor levels in AD. We have examined mu, delta and kappa opioid receptor binding parameters, binding sensitivity to a GTP analog and distribution in amygdala, frontal cortex and putamen of AD brain. Control brains were matched according to age, sex, post-mortem interval and storage time. Kd values and GTP analog binding sensitivity did not differ in AD and control brains. Bmax values for mu ([3H]DAMGE) sites also appeared unaffected by in vitro binding assays. In contrast, kappa ([3H]U69593) and delta ([3H]DSLET) opioid receptor levels, were significantly changed. In AD amygdala kappa Bmax values increased from control levels of 123 +/- 12 to 168 +/- 13 fmol/mg protein, whereas densities of kappa and delta sites were decreased from 94 +/- 8 to 48 +/- 8 and 102 +/- 3.6 to 69 +/- 8.5 fmol/mg protein, respectively, in putamen. Autoradiography revealed corresponding differences in the distribution of kappa opioid receptors. The findings indicate that the kappa binding site, which is quantitatively the major opioid receptor class in human brain, undergoes marked changes in AD amygdala and putamen.
由于阿片类药物可影响乙酰胆碱、P物质以及其他一些与阿尔茨海默病（AD）发病机制有关的神经递质的释放，因此评估AD患者脑中阿片受体水平具有重要意义。我们检测了AD患者脑杏仁核、额叶皮质和壳核中μ、δ和κ阿片受体的结合参数、对GTP类似物的结合敏感性及分布情况。对照脑根据年龄、性别、死后间隔时间和保存时间进行匹配。AD患者脑和对照脑的解离常数（Kd）值及对GTP类似物的结合敏感性无差异。μ（[3H]DAMGE）位点的最大结合量（Bmax）值在体外结合试验中似乎也未受影响。相比之下，κ（[3H]U69593）和δ（[3H]DSLET）阿片受体水平发生了显著变化。在AD患者脑杏仁核中，κ阿片受体的Bmax值从对照水平的123±12增加到168±13 fmol/mg蛋白，而在壳核中，κ和δ位点的密度分别从94±8降至48±8以及从102±3.6降至69±8.5 fmol/mg蛋白。放射自显影显示κ阿片受体分布存在相应差异。这些发现表明，κ结合位点作为人脑中数量上占主要的阿片受体类型，在AD患者脑杏仁核和壳核中发生了显著变化。
