Allen A M, MacGregor D P, Chai S Y, Donnan G A, Kaczmarczyk S, Richardson K, Kalnins R, Ireton J, Mendelsohn F A
University of Melbourne Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Ann Neurol. 1992 Sep;32(3):339-44. doi: 10.1002/ana.410320306.
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.
在人类大脑中,血管紧张素的受体结合位点存在于纹状体以及覆盖含多巴胺细胞体的黑质致密部。相比之下,血管紧张素转换酶存在于黑质网状部,并在纹状体的纹状体内富集。在本研究中,我们使用定量体外放射自显影技术,证明帕金森病患者死后大脑的黑质和纹状体中血管紧张素受体结合减少。在同一大脑中,血管紧张素转换酶的结合密度没有一致的变化。基于这些结果,我们提出,纹状体中的血管紧张素受体位于从黑质投射而来的多巴胺能终末的突触前。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相关。这些发现增加了一种可能性,即新出现的与血管紧张素系统相互作用的药物,特别是转换酶抑制剂和新型非肽类血管紧张素受体阻滞剂,可能会调节大脑多巴胺系统。