Ge J, Barnes N M
Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, UK.
Eur J Pharmacol. 1996 Feb 22;297(3):299-306. doi: 10.1016/0014-2999(95)00762-8.
The present studies assessed the levels of [125I][Sar1,ILE8]angiotensin II-labelled angiotensin AT1 and AT2 receptor recognition sites in homogenates of various brain areas (including caudate nucleus, putamen, substantia nigra, hippocampus, frontal cortex, temporal cortex and cerebellum) from patients with clinically diagnosed Parkinson's disease, Huntington's disease and Alzheimer's disease and those from age-, sex- and post-mortem delay-matched neurologically and psychiatrically normal patients. Radiolabelled angiotensin AT1 receptor recognition site levels were significantly decreased by approximately 70%, 70% and 90% in the caudate nucleus, putamen and substantia nigra, respectively, from patients with Parkinson's disease relative to matched controls. Furthermore, radiolabelled angiotensin AT2 receptor levels were decreased by some 60% in the caudate nucleus of patients with Parkinson's disease relative to control patients. In brain tissue homogenates from patients with Huntington's disease, the angiotensin AT1 receptor recognition site levels were decreased by approximately 30% in putamen relative to the control patients whilst angiotensin AT2 receptor levels were increased by some 90% in the caudate nucleus relative to the control patients. In brain tissue homogenates from patients with Alzheimer disease, the angiotensin AT2 receptor recognition site levels were significantly increased by approximately 200% in the temporal cortex relative to the control patients. The present results indicate that the reduction of angiotensin AT1 and/or AT2 receptor recognition site levels in the caudate nucleus, putamen and substantia nigra correlates with the principal neuropathology associated with Parkinson's disease and as such indicates that at least a significant population of angiotensin AT1 and AT2 receptors are located on the human dopaminergic nigrostriatal pathway. In addition, the marked increase in the levels of angiotensin AT2 receptor recognition sites in temporal cortex from patients with Alzheimer's disease correlates with some other markers associated with the renin-angiotensin system previously investigated in tissue from patients with this neurological disease.
本研究评估了临床诊断为帕金森病、亨廷顿病和阿尔茨海默病患者以及年龄、性别和死后延迟时间匹配的神经和精神正常患者的不同脑区（包括尾状核、壳核、黑质、海马、额叶皮质、颞叶皮质和小脑）匀浆中[125I][Sar1,ILE8]血管紧张素II标记的血管紧张素AT1和AT2受体识别位点的水平。与匹配的对照组相比，帕金森病患者尾状核、壳核和黑质中放射性标记的血管紧张素AT1受体识别位点水平分别显著降低约70%、70%和90%。此外，与对照患者相比，帕金森病患者尾状核中放射性标记的血管紧张素AT2受体水平降低了约60%。在亨廷顿病患者的脑组织匀浆中，壳核中血管紧张素AT1受体识别位点水平相对于对照患者降低了约30%，而尾状核中血管紧张素AT2受体水平相对于对照患者增加了约90%。在阿尔茨海默病患者的脑组织匀浆中，颞叶皮质中血管紧张素AT2受体识别位点水平相对于对照患者显著增加了约200%。目前的结果表明，尾状核、壳核和黑质中血管紧张素AT1和/或AT2受体识别位点水平的降低与帕金森病相关的主要神经病理学相关，因此表明至少相当一部分血管紧张素AT1和AT2受体位于人类多巴胺能黑质纹状体通路。此外，阿尔茨海默病患者颞叶皮质中血管紧张素AT2受体识别位点水平的显著增加与先前在该神经疾病患者组织中研究的肾素-血管紧张素系统的其他一些标志物相关。
