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Megalin binds and internalizes angiotensin-(1-7).

Publication ,  Journal Article
Gonzalez-Villalobos, R; Klassen, RB; Allen, PL; Johanson, K; Baker, CB; Kobori, H; Navar, LG; Hammond, TG
Published in: Am J Physiol Renal Physiol
May 2006

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).

Duke Scholars

Published In

Am J Physiol Renal Physiol

DOI

ISSN

1931-857X

Publication Date

May 2006

Volume

290

Issue

5

Start / End Page

F1270 / F1275

Location

United States

Related Subject Headings

  • Yolk Sac
  • Urology & Nephrology
  • Renin-Angiotensin System
  • Peptide Fragments
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Kidney
  • Humans
  • Flow Cytometry
  • Epithelium
  • Cell Culture Techniques
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gonzalez-Villalobos, R., Klassen, R. B., Allen, P. L., Johanson, K., Baker, C. B., Kobori, H., … Hammond, T. G. (2006). Megalin binds and internalizes angiotensin-(1-7). Am J Physiol Renal Physiol, 290(5), F1270–F1275. https://doi.org/10.1152/ajprenal.00164.2005
Gonzalez-Villalobos, Romer, R Bryan Klassen, Patricia L. Allen, Kelly Johanson, Chasity B. Baker, Hiroyuki Kobori, L. G. Navar, and Timothy G. Hammond. “Megalin binds and internalizes angiotensin-(1-7).Am J Physiol Renal Physiol 290, no. 5 (May 2006): F1270–75. https://doi.org/10.1152/ajprenal.00164.2005.
Gonzalez-Villalobos R, Klassen RB, Allen PL, Johanson K, Baker CB, Kobori H, et al. Megalin binds and internalizes angiotensin-(1-7). Am J Physiol Renal Physiol. 2006 May;290(5):F1270–5.
Gonzalez-Villalobos, Romer, et al. “Megalin binds and internalizes angiotensin-(1-7).Am J Physiol Renal Physiol, vol. 290, no. 5, May 2006, pp. F1270–75. Pubmed, doi:10.1152/ajprenal.00164.2005.
Gonzalez-Villalobos R, Klassen RB, Allen PL, Johanson K, Baker CB, Kobori H, Navar LG, Hammond TG. Megalin binds and internalizes angiotensin-(1-7). Am J Physiol Renal Physiol. 2006 May;290(5):F1270–F1275.

Published In

Am J Physiol Renal Physiol

DOI

ISSN

1931-857X

Publication Date

May 2006

Volume

290

Issue

5

Start / End Page

F1270 / F1275

Location

United States

Related Subject Headings

  • Yolk Sac
  • Urology & Nephrology
  • Renin-Angiotensin System
  • Peptide Fragments
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Kidney
  • Humans
  • Flow Cytometry
  • Epithelium
  • Cell Culture Techniques