Autoradiographic visualization of angiotensin-converting enzyme in rat brain with [3H]captopril: localization to a striatonigral pathway.
Autoradiographic visualization of angiotensin-converting enzyme in rat brain with [3H]captopril: localization to a striatonigral pathway.
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[3H]卡托普利对大鼠脑中血管紧张素转换酶的放射自显影可视化：定位至纹状体黑质通路。
DOI：
10.1073/pnas.81.5.1599
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发表时间：
1984
影响因子：
11.1
通讯作者：
Snyder,SH
中科院分区：
文献类型：
--
作者：
Strittmatter,SM;Lo,MM;Javitch,JA;Snyder,SH
我们用体外[~ 3 H]巯甲丙脯酸放射自显影法观察了大鼠脑内的血管紧张素转换酶（ACE;二肽基羧肽酶，肽基肽水解酶，EC 3.4.15.1）。[~ 3 H]Captopril与脑片的结合显示出高亲和力（Kd = 1.8 × 10 ~（-9）M）和与ACE活性相似的药理学特征。在脉络丛和穹窿下器官中发现非常高密度的[3 H]卡托普利结合。高密度存在于尾壳核和黑质，网状核。在脚内核、苍白球和下丘脑正中隆起中发现中等水平。在下丘脑的视上核和室旁核、内侧缰核、正中视前区和蓝斑中检测到较低水平。将鹅膏蕈氨酸或秋水仙碱注射到尾壳核中，使同侧尾壳核中的[3 H]卡托普利相关放射自显影颗粒减少85%，同侧黑质中的[3 H]卡托普利相关放射自显影颗粒减少50%以上。因此，ACE在黑质位于突触前末梢的轴突起源于尾壳核，和ACE在尾壳核位于神经元胞体或在终端的纹状体中间神经元。类似的注射到黑质的效果的缺乏证实了尾壳核注射没有引起跨突触的变化。[3 H]巯甲丙脯酸结合的存在与ACE介导的某些脑区血管紧张素II的产生一致。虽然[3 H]巯甲丙脯酸放射自显影显示ACE在纹状体黑质通路，有没有证据表明血管紧张素II参与这样的神经元通路。
We have visualized angiotensin-converting enzyme (ACE; dipeptidyl carboxypeptidase, peptidylpeptide hydrolase, EC 3.4.15.1) in rat brain by in vitro [3H]captopril autoradiography. [3H]Captopril binding to brain slices displays a high affinity (Kd = 1.8 X 10(-9) M) and a pharmacological profile similar to that of ACE activity. Very high densities of [3H]captopril binding were found in the choroid plexus and the subfornical organ. High densities were present in the caudate putamen and substantia nigra, zona reticulata. Moderate levels were found in the entopeduncular nucleus, globus pallidus, and median eminence of the hypothalamus. Lower levels were detectable in the supraoptic and paraventricular nuclei of the hypothalamus, the medial habenula, the median preoptic area, and the locus coeruleus. Injection of ibotenic acid or colchicine into the caudate putamen decreased [3H]captopril-associated autoradiographic grains by 85% in the ipsilateral caudate putamen and by greater than 50% in the ipsilateral substantia nigra. Thus, ACE in the substantia nigra is located on presynaptic terminals of axons originating from the caudate putamen, and ACE in the caudate putamen is situated in neuronal perikarya or at the terminals of striatal interneurons. The lack of effect of similar injections into the substantia nigra confirmed that the caudate putamen injections did not cause trans-synaptic changes. The presence of [3H]captopril binding is consistent with an ACE-mediated production of angiotensin II in some brain regions. Although [3H]captopril autoradiography reveals ACE in a striatonigral pathway, there is no evidence for angiotensin II involvement in such a neuronal pathway.