Characterization of the brain-specific non-AT(1), non-AT(2) angiotensin binding site in the mouse
Document Type
Article
Publication Date
8-20-2008
Publication Title
European Journal of Pharmacology
ISSN
0014-2999
Volume
590
Issue/No.
1-3
First Page
87
Last Page
92
Abstract
In the present study the existence of a non-AT(1), non-AT(2) angiotensin (Ang) binding site unmasked by the organomercurial protease inhibitor p-chloromercuribenzoate (PCMB) was demonstrated in mouse brain membranes, consistent with observations previously reported in the rat (Karamyan and Speth, 2007b). The pharmacological specificity of the non-AT(1), non-AT(2) angiotensin binding site was similar to the rat brain: Sar(1)-Ile(8)-Ang II > Ang III >or= Ang II > Ang I> p-aminophenylalanine(6) Ang II> CGP42112 >> Ang IV > Ang 1-7 congruent with shorter angiotensin fragments. Neurotensin, bradykinin, and luteinizing hormone-releasing hormone showed K(i) values >10 microM, while substance P and VIP had K(i) values of approximately 2 microM. The non-AT(1), non-AT(2) angiotensin binding site was not present in adrenal, liver or kidney. Subcellular fractionation showed a higher density of [(125)I]Ang II binding in plasma membrane (P2) fractions of cerebral cortex and hypothalamus relative to debris (P1) fractions. The binding site is present in the brains of mice in which the AT(1a), AT(1b), AT(2), Mas, and neprilysin (EC 3.4.24.11, neutral endopeptidase) was knocked out confirming that the binding site is not a heretofore described angiotensin receptor or neprilysin. These observations confirm that this novel Ang binding site is distinct from classical AT(1), AT(2), AT(4) and Ang 1-7 receptors while retaining a high specificity for angiotensins that act on the known angiotensin receptors. Whether this binding site functions as a novel receptor for angiotensins or a specific angiotensinase with variable functionality at different redox states will require further study.
NSUWorks Citation
Karamyan, Vardan T.; Gembardt, Florian; Rabey, Felicia M.; Walther, Thomas; and Speth, Robert C., "Characterization of the brain-specific non-AT(1), non-AT(2) angiotensin binding site in the mouse" (2008). HPD Articles. 82.
https://nsuworks.nova.edu/hpd_facarticles/82
ORCID ID
0000-0002-6434-2186
DOI
10.1016/j.ejphar.2008.05.035
Copyright
Copyright © 2008 Elsevier B.V. All rights reserved.
