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| Item Type: | Article |
|---|---|
| Title: | Distribution of non-AT(1), non-AT(2) binding of (125)I-Sarcosine(1), Isoleucine(8) angiotensin II in neurolysin knockout mouse brains |
| Creators Name: | Speth, R.C., Carrera, E.J., Bretón, C., Linares, A., Gonzalez-Reiley, L., Swindle, J.D., Santos, K.L., Schadock, I., Bader, M. and Karamyan, V.T. |
| Abstract: | 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 microM 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. |
| Keywords: | Angiotensin II, Iodine Isotopes, Metalloendopeptidases, Knockout Mice, Prosencephalon, Angiotensin Type 2 Receptor, Renin-Angiotensin System, Sarcosine, Animals, Mice |
| Source: | PLoS ONE |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Volume: | 9 |
| Number: | 8 |
| Page Range: | e105762 |
| Date: | 22 August 2014 |
| Official Publication: | https://doi.org/10.1371/journal.pone.0105762 |
| PubMed: | View item in PubMed |
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