Binding of 'AT receptor' ligands to insulin regulated aminopeptidase (IRAP) in intact Chinese hamster ovary cells

Autor: Demaegdt, Heidi, Gard, Paul, De Backer, Jean-Paul, Lukaszuk, Aneta, Szemenyei, Erzsébet, Tóth, Géza, Tourwé, Dirk, Vauquelin, Georges
Přispěvatelé: Department of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel (VUB), University of Brighton, Hungarian Academy of Sciences (MTA)
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Zdroj: Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology, Elsevier, 2011, ⟨10.1016/j.mce.2011.03.005⟩
ISSN: 0303-7207
DOI: 10.1016/j.mce.2011.03.005⟩
Popis: International audience; Insulin regulated aminopeptidase (IRAP) recognises "AT-receptor" ligands like angiotensin IV (Ang IV) and peptidomimetics like AL-11. The metabolic stability and high affinity of [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 [H]Ang IV, [H]AL-11 displays high affinity and specificity for IRAP in intact CHO-K1 cells as well. After binding to IRAP at the surface, [H]AL-11 is effectively internalized by an endocytotic process. Unexpectedly, surface binding and internalization of [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-receptor" ligands undergo semi-continuous cycling between the cell surface and endosomal compartments. The efficacy of stable and unstable "AT-receptor" ligands could therefore differ.
Databáze: OpenAIRE
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