Megalin binds and internalizes angiotensin-(1-7)

Megalin is a multiligand receptor heavily involved in protein endocytosis. We recently demonstrated that megalin binds and mediates internalization of ANG II. Although there is a strong structural resemblance between ANG II and ANG-(1-7), their physiological actions and their affinity for the angiot...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology. Renal physiology 2006-05, Vol.290 (5), p.F1270-F1275
Main Authors: Gonzalez-Villalobos, Romer, Klassen, R Bryan, Allen, Patricia L, Johanson, Kelly, Baker, Chasity B, Kobori, Hiroyuki, Navar, L G, Hammond, Timothy G
Format: Article
Language:English
Subjects:
Angiotensin I - metabolism
Antihypertensive Agents - metabolism
Cell Culture Techniques
Epithelium
Flow Cytometry
Humans
Kidney - physiology
Low Density Lipoprotein Receptor-Related Protein-2 - physiology
Peptide Fragments - metabolism
Renin-Angiotensin System - physiology
Yolk Sac - cytology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Megalin is a multiligand receptor heavily involved in protein endocytosis. We recently demonstrated that megalin binds and mediates internalization of ANG II. Although there is a strong structural resemblance between ANG II and ANG-(1-7), their physiological actions and their affinity for the angiotensin type 1 receptor (AT(1)R) are dissimilar. Therefore, the hypothesis of the present work was to test whether megalin binds and internalizes ANG-(1-7). The uptake of ANG-(1-7) was determined by exposure of confluent monolayers of BN/MSV cells (a model representative of the yolk sac epithelium) to fluorescently labeled ANG-(1-7) (100 nM) and measurement of the amount of cell-associated fluorescence after 4 h by flow cytometry. Anti-megalin antisera and an AT(1)R blocker (olmesartan) were used to interfere with uptake via megalin and the AT(1)R, respectively. ANG-(1-7) uptake was prevented by anti-megalin antisera (63%) to a higher degree than olmesartan (13%) (P < 0.001). In analysis by flow cytometry of binding experiments performed in brush-border membrane vesicles isolated from kidneys of CD-1 mice, anti-megalin antisera interfered with ANG-(1-7) binding more strongly than olmesartan (P < 0.05 against positive control). Interactions of megalin with ANG-(1-7) at a molecular level were studied by surface plasmon resonance, demonstrating that ANG-(1-7) binds megalin dose and time dependently and with an affinity similar to ANG II. These results show that the scavenger receptor megalin binds and internalizes ANG-(1-7).
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00164.2005