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pubmed-article:21457753pubmed:abstractTextInsulin regulated aminopeptidase (IRAP) recognises "AT(4)-receptor" ligands like angiotensin IV (Ang IV) and peptidomimetics like AL-11. The metabolic stability and high affinity of [(3)H]AL-11 for catalytically active IRAP allowed its detection in Chinese hamster ovary (CHO-K1) cell membranes in the absence of chelators (Demaegdt et al., 2009). Here, we show that, contrary to [(3)H]Ang IV, [(3)H]AL-11 displays high affinity and specificity for IRAP in intact CHO-K1 cells as well. After binding to IRAP at the surface, [(3)H]AL-11 is effectively internalized by an endocytotic process. Unexpectedly, surface binding and internalization of [(3)H]AL-11 was not affected by pretreating the cells with Ang IV but declined with AL-11. In the latter case surface expression of IRAP even increased. After elimination of simpler explanations, it is proposed that metabolically stable "AT(4)-receptor" ligands undergo semi-continuous cycling between the cell surface and endosomal compartments. The in vivo efficacy of stable and unstable "AT(4)-receptor" ligands could therefore differ.lld:pubmed
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pubmed-article:21457753pubmed:copyrightInfoCopyright © 2011 Elsevier Ireland Ltd. All rights reserved.lld:pubmed
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pubmed-article:21457753pubmed:articleTitleBinding of "AT4 receptor" ligands to insulin regulated aminopeptidase (IRAP) in intact Chinese hamster ovary cells.lld:pubmed
pubmed-article:21457753pubmed:affiliationDepartment of Molecular and Biochemical Pharmacology, Research Group of Experimental Pharmacology, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.lld:pubmed
pubmed-article:21457753pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:21457753pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed