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摘要
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 I-125-Sarcosine(1), Isoleucine(8) Ang II (I-125-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 mu M Ang II displaceable) I-125-SI Ang II binding in 32 mouse brain regions was observed. Highest levels of binding %26gt;700 fmol/g initial wet weight were seen in hypothalamic, thalamic and septal regions, while the lowest level of binding %26lt;300 fmol/g initial wet weight was in the mediolateralmedulla. I-125-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-AT(1), non-AT(2), non-neurolysin Ang II binding site in the mouse brain. Binding of I-125-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-AT(1), non-AT(2), non-neurolysin binding was also highest in the hypothalamus but had a different distribution than neurolysin. There was a significant reduction in AT(2) receptor binding in the neurolysin knockout brain and a trend towards decreased AT(1) receptor binding. In the neurolysin knockout brains, the size of the lateral ventricles was increased by 56% and the size of the mid forebrain (-22.72 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.
- 出版日期2014-8-22
- 单位东南大学
