Barnes N M, Cheng C H, Costall B, Naylor R J, Williams T J, Wischik C M
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, West Yorkshire, U.K.
Eur J Pharmacol. 1991 Aug 6;200(2-3):289-92. doi: 10.1016/0014-2999(91)90584-d.
The present study assesses the binding density of the selective angiotensin converting enzyme (ACE) radioligand [3H]ceranapril in brain tissue homogenates derived from patients with Alzheimer's disease and those from age-, sex- and post-mortem delay-matched neurologically normal patients. Saturation studies with [3H]ceranapril identified that the specific binding (defined by captopril, 10 microM) was homogenous and of high affinity. ACE inhibitor recognition site density was higher by some 70% in the temporal cortex (Brodmann area 22) from Alzheimer's patients whereas densities were similar in frontal cortex and cerebellum when compared to control tissue. It is unknown whether this apparently selective alteration in ACE density is directly related to, or a compensatory effect of the disease, but it provides additional support for the development of compounds which interact with the central angiotensin system as novel therapies for cognitive dysfunction.
本研究评估了选择性血管紧张素转换酶(ACE)放射性配体[3H]西拉普利在阿尔茨海默病患者脑组织匀浆以及年龄、性别和死后延迟相匹配的神经功能正常患者脑组织匀浆中的结合密度。用[3H]西拉普利进行的饱和研究表明,特异性结合(由10 microM卡托普利定义)是均匀的且具有高亲和力。与对照组织相比,阿尔茨海默病患者颞叶皮质(布罗德曼22区)的ACE抑制剂识别位点密度大约高70%,而额叶皮质和小脑的密度相似。目前尚不清楚ACE密度这种明显的选择性改变是与疾病直接相关,还是疾病的一种代偿效应,但它为开发与中枢血管紧张素系统相互作用的化合物作为认知功能障碍的新型疗法提供了额外支持。