ANGIOTENSIN-II RECEPTOR-BINDING ASSOCIATED WITH NIGROSTRIATAL DOPAMINERGIC-NEURONS IN HUMAN BASAL GANGLIA
ANGIOTENSIN-II RECEPTOR-BINDING ASSOCIATED WITH NIGROSTRIATAL DOPAMINERGIC-NEURONS IN HUMAN BASAL GANGLIA
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DOI：
10.1002/ana.410320306
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发表时间：
1992-09-01
影响因子：
11.2
通讯作者：
MENDELSOHN, FAO
中科院分区：
文献类型：
--
作者：
ALLEN, AM;MACGREGOR, DP;MENDELSOHN, FAO
在人脑中，血管紧张素的受体结合位点存在于纹状体和覆盖含有多巴胺的细胞体的黑质致密部中。相反，血管紧张素转换酶出现在黑质网状部，并在纹状体的纹状体中富集。在这项研究中，使用定量体外放射自显影技术，我们证明了帕金森病患者死后大脑黑质和纹状体中血管紧张素受体的结合减少。在相同的大脑中，与血管紧张素转换酶的结合密度没有表现出一致的变化。根据这些结果，我们认为纹状体中的血管紧张素受体位于突触前从黑质突出的多巴胺能末端。相比之下，这些结果支持了先前在大鼠中的研究，表明血管紧张素转换酶与投射到黑质网状部的纹状体神经元有关。这些发现提出了一种可能性，即与血管紧张素系统相互作用的新兴药物，特别是转化酶抑制剂和新型非肽血管紧张素受体阻滞剂，可能会调节大脑多巴胺系统。
In the human brain, receptor binding sites for angiotensin are found in the striatum and in the substantia nigra pars compacta overlying dopamine-containing cell bodies. In contrast, angiotensin-converting enzyme occurs in the substantia nigra pars reticulata and is enriched in the striosomes of the striatum. In this study, using quantitative in vitro autoradiography, we demonstrate decreased angiotensin receptor binding in the substantia nigra and striatum of postmortem brains from patients with Parkinson's disease. In the same brains the density of binding to angiotensin-converting enzyme shows no consistent change. We propose, from these results, that angiotensin receptors in the striatum are located presynaptically on dopaminergic terminals projecting from the substantia nigra. In contrast, the results support previous studies in rats demonstrating that angiotensin-converting enzyme is associated with striatal neurons projecting to the substantia nigra pars reticulata. These findings raise the possibility that newly emerging drugs that interact with the angiotensin system, particularly converting enzyme inhibitors and new nonpeptide angiotensin receptor blockers, may modulate the brain dopamine system.