Distribution of non-AT1, non-AT2 binding of 125I-sarcosine1, isoleucine8 angiotensin II in neurolysin knockout mouse brains.
Distribution of non-AT1, non-AT2 binding of 125I-sarcosine1, isoleucine8 angiotensin II in neurolysin knockout mouse brains.
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DOI：
10.1371/journal.pone.0105762
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Karamyan VT
中科院分区：
文献类型：
--
作者：
Speth RC;Carrera EJ;Bretón C;Linares A;Gonzalez-Reiley L;Swindle JD;Santos KL;Schadock I;Bader M;Karamyan VT
最近鉴定出血管紧张素 (Ang) II 的一个新结合位点，即肽酶神经溶素 (E.C. 3.4.24.16)，这对肾素-血管紧张素系统 (RAS) 具有重要意义。本报告使用定量受体放射自显影技术描述了神经溶素敲除小鼠大脑中 125I-肌氨酸 1、异亮氨酸 8 Ang II (125I-SI Ang II) 的特异性结合分布与野生型小鼠大脑的比较。在对氯汞苯甲酸 (PCMB) 存在的情况下，发现了新的结合位点，观察到特异性（3 µM Ang II 可置换）125I-SI Ang II 结合在 32 个小鼠大脑区域中广泛分布。下丘脑、丘脑和间隔区域的最高结合水平>700 fmol/g初始湿重，而最低结合水平<300 fmol/g初始湿重出现在中外侧延髓。与神经溶素敲除大脑相比，野生型小鼠大脑中的 125I-SI Ang II 结合平均高出 85%，这表明小鼠大脑中存在额外的非 AT1、非 AT2、非神经溶素 Ang II 结合位点。在 PCMB 存在的情况下，125I-SI Ang II 与神经溶素的结合在下丘脑和腹侧皮质大脑区域中最高，但广泛分布于所有调查区域。非 AT1、非 AT2、非神经溶素结合在下丘脑中也最高，但分布与神经溶素不同。在神经溶素敲除大脑中，AT2 受体结合显着减少，并且 AT1 受体结合有减少的趋势。在神经溶素基因敲除的大脑中，侧脑室的大小增加了 56%，中前脑的大小（相对于前囟为-2.72 至 +1.48）增加了 12%。这些结果证实了神经溶素作为一种新的血管紧张素II结合位点的身份，表明神经溶素可能在对抗大脑RAS的病理生理作用和影响大脑形态方面发挥重要作用。
The recent identification of a novel binding site for angiotensin (Ang) II as the peptidase neurolysin (E.C. 3.4.24.16) has implications for the renin-angiotensin system (RAS). This report describes the distribution of specific binding of 125I-Sarcosine1, Isoleucine8 Ang II (125I-SI Ang II) in neurolysin knockout mouse brains compared to wild-type mouse brains using quantitative receptor autoradiography. In the presence of p-chloromercuribenzoic acid (PCMB), which unmasks the novel binding site, widespread distribution of specific (3 µM Ang II displaceable) 125I-SI Ang II binding in 32 mouse brain regions was observed. Highest levels of binding >700 fmol/g initial wet weight were seen in hypothalamic, thalamic and septal regions, while the lowest level of binding <300 fmol/g initial wet weight was in the mediolateral medulla. 125I-SI Ang II binding was substantially higher by an average of 85% in wild-type mouse brains compared to neurolysin knockout brains, suggesting the presence of an additional non-AT1, non-AT2, non-neurolysin Ang II binding site in the mouse brain. Binding of 125I-SI Ang II to neurolysin in the presence of PCMB was highest in hypothalamic and ventral cortical brain regions, but broadly distributed across all regions surveyed. Non-AT1, non-AT2, non-neurolysin binding was also highest in the hypothalamus but had a different distribution than neurolysin. There was a significant reduction in AT2 receptor binding in the neurolysin knockout brain and a trend towards decreased AT1 receptor binding. In the neurolysin knockout brains, the size of the lateral ventricles was increased by 56% and the size of the mid forebrain (−2.72 to +1.48 relative to Bregma) was increased by 12%. These results confirm the identity of neurolysin as a novel Ang II binding site, suggesting that neurolysin may play a significant role in opposing the pathophysiological actions of the brain RAS and influencing brain morphology.
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DOI：
10.1111/j.1432-1033.1992.tb17168.x
发表时间：
1992-08-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
DAHMS, P;MENTLEIN, R
通讯作者：
MENTLEIN, R
影响因子：
5.5
作者：
FELDBERG, W;LEWIS, GP
通讯作者：
LEWIS, GP
影响因子：
6.3
作者：
Fleegal-DeMotta, Melissa A.;Doghu, Shinya;Banks, William A.
通讯作者：
Banks, William A.
影响因子：
3.8
作者：
BRASZKO, JJ;KULAKOWSKA, A;WISNIEWSKI, K
通讯作者：
WISNIEWSKI, K
影响因子：
2.9
作者：
Karamyan, Vardan T.;Speth, Robert C.
通讯作者：
Speth, Robert C.